dr Milan Ignjatovi

IGNJATOVII
40GODINAUPSIHIJATRIJI

Vrac
2017

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Posveeno mojim roditeljima.

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IGNJATOVII
40GODINAUPSIHIJATRIJI

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AGORAPHOBIA WITH PANIC DISORDER - FAMILY
PSYCHOPHARMACOTHERAPY BY PAROXETIN

AUTHORS
Milan Ignjatovi, MD, Psychiatric Medical Office, Health Care Center, Bansk Bystrica
MUDr. Dana Ignjatoviov, Psychiatric Department, F. D. Roosevelts Hospital, Bansk Bystrica

SUMMARY
4 women 55-year-old mother and her two daughters: 38 and 34 years old and one stepdaughter 20 year old were followed
and used in casuistics.
To make good quality family anamnesis is very impotant for risks family factors and for detection of psychical disorders.
The ways of heredity are: polygenic modeli, model of the dominant gene with incomplete penetration, autosomal dominant
model and the others.
There are many genetic hypothesis about genesis of the psychical disorders and genetics markers like: yohimbin, clonidin,
coffein, infusion of natrium lactatum, hyperventilation, L-tryptofan, benzodiazepins receptors, continuity between mitral prolaps
and panic disorder, positive response on antidepressants, personality studies of the patients with panic disorder (Eri Lj., 1991).
The problem is that patients didnt know about their disorder, about treatment, etiology, complications and consequences.
Treatment by psychopharmacotherapy confirms some of genetic hypothesis connected with correct diagnosis.
These 4 women were diagnosticated and adequately treated in our Psychiatric Medical Office, Health Care Center.

KEY WORDS
Agoraphobia with panic disorder, paroxetinum, genetic studies

INTRODUCTION
Long time ago, in the past century, when genetic research was not carried out, Beard wrote about consequent predispo-
sition for the occurrence and development of neurasteny.
Freud came up with similar experience and he pointed out the fact that neurosis of fright has the same symptoms among
several family members. Oppenheimer and Rothshild found out that family history of neurosis existed among 45% of observed
World War I soldiers who were diagnosed with Da Costa syndrome. Some time later, during the World War ll, Wood found po-
sitive family history among 25% patients treated on heart neurosis.
Subsequent researches showed that panic disorder is a disease, which cumulates in the family.

METHODOLOGY AND GROUP OF PATIENTS

4 female patients were chosen for the casuistic study on the basis of 5 including criteria: 1. Biographical anamnesis, 2.
Forgoing diariosis 3. Current diagnosis, 4. Therapy, 5. Family relationship.
Observation and evaluation of results was carried out from October 1999 to March 2000, while all of the female patients
continue will the therapy and they are registered in our medical office.

OBSERVATION
The results are based on retrospective clinical observation of patients medical records where the focus was on the bio-
graphical anamnesis, diagnosis, therapy and family relationship.
The core of the study is formed by 4 casuistic cases which draw the importance of genetic factors for the occurence and
development of panic disorder.

CASUISTIC No. 1
55 years old woman, worker, mother of three daughters, long term treated in different medical offices with diagnosis of
neurasteny. She visited our medical office on the recommendation of both of her daughters. She describes her first panic
attack as the situation when she had her middle daughter and she couldnt go for a walk with the buggy (in the year 1966), she
was dizzy and weak, she couldnt take anything into her hands, she had palpitations, was stifled, sweated, had pins and need-
les in her hands, felt a node in her throat and she helped herself by giving snow on her head. Afterwards she was scared to go
for a walk. Physicians prescribed chlordiazepoxidum (Radepur) and ergotamini tartas, belladonnae radicis, phenobarbitalum
(Bellaspon) for her and symptoms were gone for one or two days. Her husband didnt believe her that she was ill and he was
furious of her status. That all enhanced her tension and the patient was not even able to stand up from her bed because of the
dizziness. She was scared to visit a physician in the psychiatry ward at that time. First time she visited psychiatric medical offi-
ce in Brezno 20 years ago, she was taking chlordiazepoxidum (Elenium), ergotamine tartas, belladone radicis, phenobarbitalum
(Bellaspon) and diazepanum (Seduxen). When her youngest daughter was born, she felt quite well during the daytime but she
got an attack after night shift. She described the attack like is: she woke up in the night, didnt know where she was, what she

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was doing, she was steamy and very afraid. When her husband was close to her, she composed herself but in spite of this she
was not able to leave the bed.
She had to be very responsible in her job, millions were at stake, fortunately nothing happened.
She was treated in the spa town of Vyn Rubachy since 1992. She felt very well in the baths because it was a peaceful pla-
ce. She was sent to visit a primary doctor 5 years ago who prescribed alprazolam (Neurol) and fluoxetinum (Prozac) for her.
She felt better, even though she still used to have panic attacks which were more mild and weaker. She concluded the combi-
nation of noted drugs because her physician changed one drug to fluoxetinum (Deprex).
She had strong diarrhea, strong headache and she felt sick after using this drug. The patient visited our medical office on
December 12, 1999 with no psychopharmacological medication. We prescribed lire medication of paroxetinum and clonaze-
pamum for her. The patients status improved very quickly (in 2 weeks time), she didnt have any attacks any more, her mood
brightened, she slept all the night, and she hasnt been scared of people any more. After one month the dermatologist diagno-
sed her with allergy to paroxetinum. Thats why this drug was replaced by citalopramum. Tte patient canceled the medication
of citalopram by herself and on the recommendation of her three daughters she started taking paroxetinum and clonazepamum
during the last control visit on the March 16, 2000. No allergy to paroxetinum occurs at present and previous allergic reactions
are thought to be possible comorbidity with allergy e.g. to another drugs or food. The patient evaluates her status as excellent
and she assesses the current therapy as the most sufficient and the most successful in 30 years of treatment.

CASUISTIC No. 2
38 years old female patient, single, lives with her partner who is addicted to alcohol and is aggressive when drunk. Currently
the patient tries to evacuate him from her flat a legal way. The patient was treated by psychiatrist for a long time. She was not
satisfied with the treatment and thats why she visited our medical office on other patients recommendation.
The memories of her childhood are connected to her mother who lived with the children alone, she was divorced, she ra-
ised the children quite strictly. The patients father drank a lot of alcohol, she remembers that he even attacked them with a
gun and he threatened to shoot them all. Her mother was very sick, she moved to her grandmother and she got married for
the second time. The patient couldnt sit down under the facts the underwent in her childhood. When she cut adrift she got a
flat and she took an alcoholic man to her flat. She wants to get him away in a legal way now. When the patient visited our medi-
cal office for the first time, she had the following symptoms: palpitation, exudation, fear that disallowed her to go to the work,
trepidation of hands, s le had as well as her mother a node in the throat. She got the first attack in 1994 at home, she didnt
know what that was, she felt worse and worse. Her status was so had that she couldnt even watch TV, she was even scared of
the people in TV shows. Her mother had similar symptoms. She felt a noise in heir head, she had to go to bed, couldnt go for
a shopping to the moles where a lot of people are. She stayed in the bed very often and didnt talk to people. One psychiatrist
prescribed chlordiazepoxidum (Defobin) for her. When she didnt get enough, she visited another psychiatrist, who gave her
maprotilinum (Ludiomil), alprazolamum (Neurol). In spite of that she had to call the emergency very often or had to visit the
emergency by herself, she got hypertension, couldnt compose herself. We registered her with the diagnosis of neurasteny and
put her on paroxetinum and
clonazepamum right after her first visit in our medical office. Between the first and the second week her health status impro-
ved, attacks receded, she started to go for a shopping, wasnt scared of people anymore. She also attended the group therapy in
our medical office. When she started to have conflicts will her partner, her health status got worse. The patient received shoots
of progesterone and estradioli benzoas from the year 1980 because sometimes she didnt have menstruation up to 3 months.
Since she has been treated by paroxetinum, her menstruation is periodical. Meanwhile the patient received the verdict which
states that her partner has to move from her flat. The patient is looking for a new job because nobody believed in her invisible
illnesses in her former job. She evaluates her status as good, stabilized and the treatment as successful.

CASUISTIC No. 3
34 years old female patient, previously unemployed, married. For the first time she got palpitation after the wedding in 1986.
She couldnt breathe and her health status started to worsen after 3 years. She started to feel sicker since she became unem-
ployed. Since she finished only elementary school, she studied at the school for waiters but in fact she had stage fright and was
very self-centered, she didnt finish the school for waiters. She doesnt remember her father because her parents got divorced
when she was 4 years old. She describes her symptoms as weakness, shakiness, vertigo, chest pains, shaking of her legs. She
feels better when she stays at home in silence. Her husband drinks alcohol and when drunk, he upbraids her the fact that she
is unemployed. She adds to her symptoms that she couldnt breathe; she felt the way she would suffocate. These symptoms
appeared when her daughter, who had legs desjointedness and didnt sleep at night, was born. That was a huge endurance for
her. When the patient tended her daughter to the school, she felt she wouldnt return home and would vomit. There were more
panic attacks upraised during one week and she felt she would get heart attack. When she worked as a cleaner in an elementary
school, she felt good in a collective of colleges. She felt the worst when she had to stay at home alone. She underwent diffe-
rent medical examinations but nothing was found. Afterwards she started to be scared of people and thats why she didnt go
abroad (she didnt travel by bus, didnt go for a shopping). There is comfort at home, its worse when the husband gets drunk
and offends her. The neurologist put her on paroxetinum. Even though her health status improved, the patient stopped the
treatment by herself because the period of menstruation shortened up to 15 days.
The patient was examined in our medical office for the first time on the recommendation of her mother and two sisters in
February and she had the following symptoms: hands shakiness, enhancing anxiety, node in the throat, she was scared of going

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outside, felt better at home. After the introductory interview we agreed on be therapy of paroxetinum and clonazepamum..
After one month the patient notes that her health status improved, she has no panic attacks, she meets people and she evalu-
ates the treatment as the best one so far.

CASUISTIC No. 4
20 years old female patient, trained tailor, the youngest one in the proximity. After the childbirth in 1988 she began to have
vertigo, palpitation, body shakiness and was scared of going out for a shopping. She had these attacks more than 4 times a month.
Unlike her mother and stepsisters, she didnt have a node in her throat. When she restored from the smallpox in her childhood,
she was diagnosed with the epilepsy. The patient states that she used to faint, she sensed everything around but couldnt res-
pond. She visited a neurologist who put her on phenytoinum and carbamazepinum. Then the pediatric neurologist put her on
natrium valproate when she was 12 years old. Gradually acidum valproicum + natrii valproas (Depakine Chrono 500) of a dose
of 1 tablet in the morning - 1 tablet in the noon - 1 tablet in the evening were added to the therapy management. Phenytoinum
was rejected, natrium valproat (Orfiril 300 mg in one tablet) of a dose of 1 tablet in the morning - no tablet in the noon - 1 tablet
in the evening was kept. When the patient attended the 7th grade of the elementary school, she had vertigo during the lessons,
she asked for going to the toilet very often and she felt very badly during the biology classes when they learned about blood.
She was hospitalized during that period of time. When medical staff told her about the blood sample testing, she fainted. She
was scared of going to school, her classmates laugh at her because of her epilepsy and she didnt remember anything after each
attack. At home the attacks started to appear during the night. She got shakiness and her mother had to wake her up. She had
vertigo in the classroom very often. Moreover she fabled and fell down at home. She used to faint more often in school, especi-
ally in the period of examinations; she fainted more often at home as well at that time. She has never had enuresis and has ne-
ver bitten her tongue. The epileptic attack lasts for 1 minute and she has never slept after the injection of diazepamum or after
the attack. When she got very painful menstruation, she felt she would suffocate and they called the ambulance immediately.
The patient had no attacks at the secondary school. No attacks were present at home at that time either. She visited a pedia-
tric neurologist for the first time when she was 11, panic attacks uprose when she was 12 years old. Even though she was taking
phenytoinum and carbamazepinmu, she fainted at home as well as at school. She felt badly all the time. Suddenly, the attacks
were gone when she was in the 8th grade of the elementary school. Palpitation appeared at home when she was 12 years old,
she didnt tell her parents about it, she just retired to her room and went to bed. She lists more exact medication since her age
of 16, when she received natrium valproas (Orfiril 300 mg in each tablet) in a dose of 1 tablet in the morning - no tablet in the
noon - 1 tablet in the evening. When she was 18 years old she was taking acidum valproicum + natrii vaiproas (Depakine Chrono
500) in a dose of 1 tablet in the morning - 1 tablet in the noon -1 tablet in the evening. The attack uprose in the dormitory when
she was 16 years old. It was seldom and as she states further, there have been no more attacks at home or at secondary school.
She got married at the age of 18; she gave birth to a daughter in 1983 and 3 days after the childbirth she fainted lying in the
bed. Wien she rinsed pampers or when she woke up to get pills, the attacks returned. She got aura and consequently fainted
when she saw the strips on the tiles. Prolonged observation of the blue strips on the tiles provoked this kind of schism. After
that accident her mother didnt let her staying at home alone, she was with her daughter even when she was having a shower.
To help herself, the patient doesnt look at those strips when she is in the bathroom. When her oldest sister remembered the
incidents with the bathroom, we found out that she used to lock the patient in the bathroom as a punishment when she beha-
ved badly in her childhood. She haunted the patient to leave her inside the bathroom for good in this time of her childhood.
This fact was confirmed also by the middle sister. The patient is 20 years old now, last time she fainted in maternity hospital
one year ago. Approximately half year after her child was born she began to have vertigo, uncertain walking, everything was
spinning around her, she sweated. These feelings attacked her 4 times a month. Since the patient milked her child, her health
status worsened during each menstruation period. She visited our medical office on the recommendation of her stepsister on
the November 3, 1999. Her stepsister suggested her to visit the psychiatrist for a long time. The patients status improved after
two weeks of medication of paroxetinum and clonazepamum, she has had no more anxiety nor panic attacks. Whereas the pa-
tient is listed in neurological office, we mutually consulted the therapy and recommended to reduce eventually to cancel the-
ir therapy. After the arrangement we stopped the management of natrium valproas (Orfiril), we reduced the dose of acadum
valproicum + natrium valproas (Depakine Chrono 500) up to 1/2 tablet in the morning - no tablet in the noon - 1 tablet in the
evening. Patient feels good, the health status is stabilized, she takes care of her daughter with joy, handles with common acti-
vities without any probifems, she evaluates the treatment as being successful.
Each of these 4 patients evaluated the treatment of their mothers, sister and stepsister separately, so besides subjective
evaluation we have heteroanamnestic (heterologic history) evaluations as well.

SUMMARY
4 women, a mother and 3 daughters who were chosen according to 5 including criteria are inncluded in the casuistic study,
whereas 2 sisters were their own, one was a stepsister. The average age was 36,75 years. Symptoms were present in average of
16,25 years and treatment in our medical office tasted 3 months in average.
There has been used paroxetinum in a dose of 30 mg per day and clonazepamum in a dose of 0,5 up to 1,5 mg per day in-
dividually in the treatment.
The results were analyzed on the basis of patients subjective evaluation as well as according to the heteroanamnestic evaluation.

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DISCUSSION
Family studies and studies realized on twins who suffer from anxiety and panic attacks show that panic disorder is familiar
disease. However, family cumulation is neither sufficient nor necessary condition to confirm that the disorder is congenital. It
is necessary to look through the exact pathway of genetic transmission, but we have not reached definitive conclusion up to
now. There are several models available; polygenous model, model of dominant gene with incomplete penetration, autozom
dominant model. The results of the researches done up to now show that the model of dominant gene with incomplete pe-
netration is the most feasible way of genesis and development of panic disorder, but the model of polygenous heredity is also
not definitely rejected. We have investigated the model of polygenous autozom dominant heredity in our study. The results we
have reached suggest that panic disorder is transmitted as an autozom dominant disorder (1). Family studies of the panic dis-
order realized in 1980s show that the risk of uprise is 17,3% in first grade relatives and added risk from 7,4% for possible panic
disorder (which uprises with 2,3 rarely with 4 symptoms of the panic disorder criteria).
Some authors have found out high risk of panic disorder in both groups of relatives in a case of panic disorder (17,3%) and
in groups of relatives in a case of agoraphobia (8,3%), compared to 4,2% in control group. (2)
Other studies found out from 4 to 8 higher risk of panic disorder in the group of first grade relatives of patients with panic
disorder diagnosis compared to first grade relatives of patients with other psychical disorders. (3)
Having gone through the all aspects of genetic research of anxiety and panic disorder, the problem how to explain them
still remains.
In spite of evidences that panic disorder is family disease, as well as there is high concordance in monozygote twins, patho-
physiological mechanisms of panic disorder development have been determined. We dont have sufficient feasibility to define
the role of genetic factors in panic disorder etiology for certainty.
What is really proved is the fact that anxiety and panic disorder are not inherited by the simple principle of Mendelejev he-
redity rules. It is proved that a lot of anxious conditions occur in the participation of psychological, social and cultural factors
without the visible contribution of genetic factors.
There is a model of possible panic disorder uprise and development, in which the biological, psychological and social factors
are comprehensively present and the model is based on those proved facts.
Truly, nonspecific genetic predisposition in cooperation with psychological factors leads into the uprise and development
of anxious conditions.
In this kind of explanation the questions about the nature, noted genetic predisposition come out. In other, more simple,
words, what is inherited in the case of anxious conditions and panic disorder and if children of patients with panic disorder in-
herited the same disorder.
The majority of research scientists suggest that the cacoethes and hypersensitiveness for the uprise and development of
anxious conditions are inherited and they are based on enhanced autonomous nervous system reactivity or on the unstablene-
ss of neurotransmitter system that determines the global organism reactivity.
Meanwhile, the existence of cacoethes and hypersensitiveness for the anxious conditions suprise and development doesnt
mean sure disease development. Maybe the cacoethes is anchored in development basement of known personality of type A,
by whom the essential hypertension is developing. The essential hypertension could be followed by the existence of anxiety
but it couldnt be as well.
It is also possible that the cacoethes just reduces threshold for specific senses and activities which, in cooperation with
psychological factors, lead into the disease onset. This kind of explanation can be only the peak of the enhanced reactivity
basement to the stress or can bean anxiety manifestation. It was proved by many researches that only features of personality,
such as flap, tendency to react anxiously, hypersensitiveness and shyness are inherited. It is proved that neuroticism as perso-
nality feature is inherited. Other authors have found out that personality feature highly correlates in twins couples, no matter
if they have grown up together or not. The high correlation of personality features for anxiety in monozygote twins couples
have been proved, meanwhile it hasnt been proved in dizygote twins couples.
A personality that has anxious features (anxious character) goes through unpleasant psychosocial factors or through stress
with anxious reactions. The way to the symptoms of panic attacks and panic disorder is very short when a long term and inten-
sive fear comes out. Finally, children of patients who are diagnosed with panic disorder do not straightaway inherit the same
disorder. However, even this fact cant he certainly confirmed.
50% of daughters and 10% of sons who suffer from panic disorder have symptoms which permit to make the right diagnosis.
In conclusion, we have to state that geneticists have not said the final word on the confirmation of basement for panic dis-
order uprise and development.
Researches in the area of molecular biology are at the center of attention.
Preliminary results of 29 genetic markers of 26 families with positive history of panic disorder have been reported and they
have shown that there is a connection between panic disorder and patients chromosome status, especially in chromosome 16
and 22.
Implementation of this new technology into genetic research of patients with panic disorder and twin couples with certain
disease has allowed us to accept genetic basement of panic disorder uprise and development as comprehensive problem. The
results that should be found out are expected with great attention.

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CONCLUSION
Thanks to patients who suffer from panic disorder and thanks to enthusiasm in psychiatry, positive family history of certain
disorder, disease can be helpful for early diagnostic testing and for sufficient therapy.
Everything we are supposed to do is to get quality family history.

BIBLIOGRAPHY
1. Eri Lj., 1991: Priina stanja, II dopunjeno i proireno izdanje, Beograd- Zagreb, 1 309:
56- 57, 67- 69
2. Hales R.E., Yudovsky S.C., Talbott JA., 1994 Textbook of psychiatry, 2-nd Edition,
The American Psychiatric Press, 1-, 1608, 37- 71
3.Raboch J., Prako J., Seifertov D., 1999: Panick stavy II dl, vyd. SKB, 6- 56: 29

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ACAMPROSATE FOR OUT-PATIENT ALCOHOL DEPENDENCE
TREATMENT

AUTHORS
Dana Ignjatoviov, 1, M.D.
Milan Ignjatovi, 2, M.D.
Jasmina Jankovi-Gaji, 3, M.D.

1- Psychiatric Out-Patient Clinic, Health Centre Bansk Bystrica, Slovakia

2- Psychiatric Out-Patient Clinic, Health Centre Bansk Bystrica, Slovakia
3- Dragia Miovis Psychiatric Clinic KBC, Belgrade, Yugoslavia

SUMMARY
The number of patients treated for the alcohol dependence syndrome at the psychiatric clinic increases. Their drinking has
a serious impact on their families and professional lives and it represents a complex medical, social, and economic problem.
Various methods of treatment of the alcohol dependence syndrome have been used in psychiatry, and currently we can
combine them or use new preparations, designed specially for specific kinds of dependence.
One of the latest substances used as anti-craving agents is calcium acetylhomotaurinate, also known as calcium acetyl ami-
nopropanesulfonate or acamprosate.
In our study, we have tried to establish whether acamprosate can be helpful in the treatment of the alcohol dependence
syndrome.
We have included 23 patients into our study, 9 women and 14 men, who were monitored from 1st January 2001 to 31st
October 2001. The average period of drinking was 10.47 years (the shortest one 2 years, the longest one 39 years), with an ave-
rage duration of abstinence of 7.52 months (the shortest one 58 weeks, the longest one 10 months). The average age of the pa-
tients was 43.26 years (ages ranging from 27 to 59 years). 5 patients interrupted their abstinence after they had started to use
acamprosate, 3 of them after less than three months of abstinence and 2 patients after longer than 3-month abstinence. None
of the patients interrupted their treatment by acamprosate due to adverse side effects of the drug.

KEY WORDS
alcohol dependence syndrome, acamprosate, SSRI, period of drinking, duration of abstinence.
break of abstinence, relapse

INTRODUCTION
The alcohol dependence syndrome includes a number of physiological, behavioural and cognitive phenomena, in which the
use of a certain substance or substances by an individual becomes more significant than any other behaviour patterns that
were previously of a higher value.
The basic described characteristic of the alcohol dependence syndrome is the longing or craving (often strong, almost unbe-
arable) for the use of a drug (which is or is not medically prescribed), like alcohol or tobacco.
There is evidence that the resumption or the use of the substance after a period of abstinence leads to faster re-discovering
of the developed manifestations of the syndrome when compared to individuals who are not addicted.
The following are diagnostic criteria for the dependence syndrome according to ICD- 10:final diagnosis of dependence should
be made only when 3 or more of the following nenomena have been experienced or have manifested themselves in the past year:
Strong longing for or temptation to use a substance;
More difficult control over own behaviour, linked with the use of the substance in terms of the start of the use, end of the
use, or quantity of the used substance;
Physiological abstinence syndrome after the use of the substance ended or was decreased, proved by an abstinence syn-
drome characteristic for that substance, or when the same (or similar) substance is used with the intention to reduce or over-
come abstinence symptoms;
Proof of the tolerance in a way in which increased doses are necessary to achieve effects (results) that were previously
achievable by lower doses (a good example of that is people dependent on alcohol or opiates, who can used daily doses of such
substances that would be sufficient for devastating or killing other users without developed tolerance);
Progressive neglecting of alternative ways for satisfying interests due to the use of the substance, increasingly longer time
necessary for the obtaining and use of the substance, as well as for resting an recovery from its effects;
Carrying on with the use of the substance despite the awareness of clear facts about its harmful consequences, like liver
damage due to excessive use of alcoholic drinks, depressive mood that follows periods of intensive use of the substance or
damage of the cognitive functioning connected with the use of drugs. It is necessary to insist it is specified whether the user
has realized or it can be expected he/she will realize the basis as well as the mechanism of the harmful effect of the substance.

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 The decrease of the personal repertoire of patterns for the use of a psychoactive substance is also described as a typical
characteristic (e.g. tendency to drink alcoholic drinks in the same way during week days as during weekends, irrespective of
social limitations that set norms for behaviour connected with drinking);
The basic characteristic of the alcohol dependence syndrome is the existence of a substance that is used or the existence
of a desire, craving for using the drug.
We meet with an individuals subjective realization that he/she is tempted to use a substance most frequently during a test
aimed at ending or controlling the use of the substance.
Such a diagnostic procedure excludes, for example, surgical patients who are administered pain relieving opium preparati-
ons and who may show symptoms of opiate abstinence syndrome after the administering of drugs has been interrupted, and
who are do not crave for further use of the given therapy.
The dependence syndrome can be characteristic for a certain substance (like, for example, tobacco, diazepam) for a group
of substances (e.g. opiates, opiate drugs), or for a wider range of different substances, like in the case of some individuals who
feel temptation to take any substance (drug) that is available for them, which is manifested by their restlessness, agitation or
physical symptoms of the abstinence syndrome when they do not take the drug.
According to Otto M. Lesch, there are 4 subtypes of alcoholism that are significant for diagnosing and therapy of the alcohol
dependence syndrome. The least possible to influenceand treat are the 4th type (connected with organic brain disorders) and
the 3rd type (connected with severe mental disorders), while the 2nd type (connected with anxiety) and the 1 st type (connec-
ted with habits in the population) are most easily possible to diagnose and treat.
There are also other classifications, in which development stages are specified, from the initial one, through the prodromal
one and the crucial one, to the terminal (chronic) one (according to professor Dobi), as well as the division of dependences
according to Jellinek into the alpha, beta, gamma (most frequently dealt with at the psychiatric clinic), delta and epsilon types
(Skal 1987).
Psychopharmacotherapy of the alcohol dependence syndrome has its history, including substances ranging from those with
an aversive effect to those with an anti-craving effect, and recording a lot of contradictory results (Bankole A. Johnson, 2000).
Large studies with acamprosate, including thousands of patients, have been conducted (Mason B. et al., 2000), and there
have also been some others that included more than 100 patients (Pelc 1., 1997). Sociotherapeutical meetings, as an auxiliary
method, have been reported.
Substances that have been used in the treatment of the alcohol dependence syndrome include opioid receptor antagonists
(naltrexone, nelmefene) (Wilde, 1997), NMDA antagonists (calcium acetylhomotaurinate - acamprosate (Monografia, 2000),
serotonergic substances, including SSR1, out of which fluoxetine (Naranjo CA, 1990), fluvoxamine and citalopram (Naranjo CA.,
1987, Naranjo CA, 1992), 5HT1 partial agonists (buspirone), 5HT2 antagonists (ritanserine, amperozide), 5HT3 antagonists (on-
dansetron) (Bankole A. Johnson, 2000, Wilde, 1997), dopamine antagonists (haloperidol, tiaprid), which can be used for relie-
ving abstinence symptoms, (Evens M., 1980), or completely new substances that influence delta receptors (ICI 174864, naltriben
and naltrindole) (Froehlich JC, 1991), or other -opioid antagonists (nalmefene), have been used in most studies.
Furthermore, calcium channel blockers (isradipin) (Rush CR, 1998), natural preparations from the roots of a Chinese plant
peuraria lobata (puerarin), with which no trials have been conducted on people yet, as well as neuropeptide Y, which shows
anxiolytic effects in animal studies (Ehlers CL, 1998), have been used.
Combinations of various psychopharmaceuticals, like acamprosate with disulfiram, are also used, but the combination of
naltrexone with disulfiram is not recommended, while, on the theoretical level, there are some views in favour of combining
naltrexone with fluoxetine and SSRI with naltrexone in the case of patients who suffer from a depressive disorder in co-morbi-
dity. Some pre-clinical studies point out the combination of ondansetron and naltrexone (Bankole A. Johnson, 2000).
Acamprosate (Campral) = calcium acetylhomotaurinate is a non-aversive drug, acting on the CNS, and specially developed
for maintaining long-term abstinence. Its chemical structure is similar to that of pharmacologically active arninoacids, such as
taurine, gamma-aminobutyric acid (GABA) and glutamate.
Since hypoactivity of the GABA-ergic system occurs during the chronic consumption of alcohol, acamprosate increases the
number of GABA receptors, increases GABA transmission (Monografia, 2000), and causes a reduction of the number of cal-
cium channels, which are the probable mechanisms of its effect (Wilde, 1997).Acamprosate is the first specifically acting drug
for patients with alcohol dependence syndrome after detoxification. The drug does not cause any potential acute or chronic
toxic effects. It is not addictive. Acamprosate has been approved for prescription in France since 1989, and, since later, in many
European countries (in Slovakia since 2000), as well as in Latin America, Australia, South Africa, and Hong-Kong. More than 4
million people have been treated by it (Mason 2000). The preparation could help to treat patients dependent on alcohol.
The main goal of the study was to specify an average duration of abstinence after starting to use acamprosate during a
10-month follow-up period.
Other objectives included:
Finding out an average period of drinking before an examination at a psychiatric clinic;
Time to the first drink after the start of the use of acamprosate;
Monitoring or the patients families burdening;
Completion of an anti-alcoholic treatment before an examination at a psychiatric clinic;
Monitoring of the patients personality characteristics;
Psychiatric co-morbidity;
Psychiatric therapy;

11
 Adverse effects at the start of the use of acamprosate and during its use;
Physical illnesses (epileptic seizures, liver function disorders, post-traumatic brain damage with unconsciousness and con-
cussion, ischemic heart disease, polytopic vertebrogenous algesic syndrome);
Occurrence of palimpsests, alcoholic delirium and hallucinosis;
Preference of alcohol.
As a shortcoming of this work we consider the fact that the patients started to use the drug during a 6-month period, which
is a long starting period, but which, however, was not possible to shorten in our clinical conditions;
Another shortcoming of the work is the fact that the patients GMT was not monitored or evaluated in precisely specified
time intervals; it was done only at the beginning, in the mid- term, and at the end of the 10-month monitoring of the patients.
We have not monitored the patients MCV.
The third shortcoming of the work is a relatively small group of monitored patients.

POPULATION AND METHODOLOGY

23 patients (9 women and 14 men), meeting the MKCH-10 DSM-IV criteria for the alcohol dependence syndrome - chronic,
continual condition F.I0.25 (Smolik, 1994), were identified in the patient records of two psychiatric clinics. Patients with another
psychiatric co-morbidity (F.06 - 1 patient, F.32 - 9 patients, F.34.1 - 1 patient, F.40.01 - 3 patients, F.43 - 2 patients, F.60 - 1 patient,
6 patients without any other psychiatric co-morbidity) were not excluded.
The average age of the patients was 43 26 years (from 27 to 59 years), the average period of drinking was 10.47 years (from
2 to 39 years).
The average period of drinking was 10.47 years (from 2 to 39 years).
The patients were monitored from 1st January 2001 to 31st October 2001; they started to use acamprosate between 1st
January 2001 to 30th June 2001.
The treatment of their alcohol dependence was monitored at the psychiatric clinics for the period of 10 months. Its succe-
ssfulness was evaluated by the duration of abstinence, time to the first drink, break of abstinence, and occurrence of adverse
effects during the treatment with acamprosate -- interruption of treatment due to adverse effects of the preparation.
To carry out an evaluation, we have compiled a questionnaire, which was completed by each patient included into the study.

RESULTS
The results are shown in Tables 1, 2, 3, and 4.
The average duration of abstinence of the monitored patients was 7.52 months, which can be considered as a treatment
success (according to Mason et al., 2000, who define a treatment success as complete abstinence for more than 3 months,
established by a clinical interview, normal GMT and decreased MCV).
Out of 23 patients, we have identified family burdening in 22 cases; one patients family burdening was not confirmed.
10 patients underwent detoxification at a psychiatric ward, 13 were detoxified as out-patients.
Adverse effects at the start of using acamprosate are summarized in Table 5.
None of the patients had suffered from hyper-kinetic disorder in their childhood or had previously been treated at a psychia-
tric clinic due to an anti-social personality disorder. One patient had been treated for a limit personality disorder. 3 patients
had previously been treated for anxiety disorders. 12 patients had been treated for affective disorders. One patient had been
treated as a F.06.4., and 6 patients had not been treated at a psychiatric clinic before.
14 patients suffered from physical diseases caused by their long-term consumption of alcohol. 9 patients did not.
21 patients had palimpsests and only two patients did not have them.9 patients had overcome alcoholic delirium, 14 did had
not. 2 patients suffered from alcoholic hallucinations. 21 did not.
As far as the preference of specific kinds of alcoholic drinks is concerned, 8 women preferred wine, 1 woman drank wine
and vodka, 3 men drank beer, 4 men drank beer and spirits, 2 men drank beer and wine, and 5 men preferred spirits.

DISCUSSION
Our knowledge of various classifications of the alcohol dependence syndrome that we used before 1994 and the ones we
use in todays practice, like DSM-III-R, DSM-1V, ICD-9, 1CD- 10 alcoholism subtypes according to Otto M. Lesch, or alcoholism
types according to Dobi or Jellinek, allowed us to do make more precise diagnoses and better consideration of further con-
tinuation of treatment.
Some patients are helped by outpatient treatment, combined with anxiolytics, SSRI, SNRI or atypical antipsychotics, but
other patients are not clinically motivated to abstinate after detoxification treatment, and in such cases their treatment requ-
ires hospitalization.
After the return from treatment, there are also crisis periods, which can be decisive for further abstinence (Ignjatovi M.,
Ignjatoviov D., 2001 ).
In out-patient treatment, sociotherapeutical groups, support psychotherapy, psychoeducation, and A-clubs can be helpful.
There is similar experience elsewhere at the home as well as abroad. Combined treatment is currently being offered as an
advantage. We can realize the detoxification treatment of the patient, subsequently prescribe an anti-craving drug, and include
the patient into psychotherapeutical treatment, which can result in a much better effect (Robert M. Swift, 1999, Melchior J. A.,
J. M. Hoes, 1999, Bankole A. Johnson, 2000, Pelz I. et al., 1997).

12
 There are different ways through which abstinence translates itself. Hoes specifies that a break of abstinence that lasted
less than 4 months it considered as a relapse, while a break of a longer than 4-month abstinence it called a recurrence. He also
specifies a possibility of treatment with aversive or anti-craving substances (Hoes 1999). Other authors consider abstinence
longer than 3 months as a successful one (Mason et al., 2000).
When all these views, although mutually differing, are learned, they allow better diagnosing, treatment, and support of long-
term abstinence.
Besides psychosocial possibilities to understand the issue of dependence, there are also biological aspects of the alcohol
dependence syndrome, in which the decisive role is played by the treatment with psychopharmaceuticals. Their mechanisms
of action are known, like, for example, a GABA-ergic effect, an inhibitive effect on the glutamate system, and influencing of cal-
cium channels (Michelle l. Wilde et al., 1997, Dahchour A., 2000, Bankole A. Johnson, 2000).
By using the biopsychosocial model of the illness (urik V,, 2001) in the diagnosing and treatment of the alcohol dependen-
ce syndrome, the possibilities of learning about it basis and achieving long-term abstinence are widened.As it is pointed out in
our study, patients need to he cared for individually, examined thoroughly and recommended for adequate treatment. The re-
sult is the duration of their abstinence as well as the subsequent improvement of the quality of their lives. In comparison with
the previous methods of treatment, for example by disulfiram, serotoninergic substances, or naltrexone, acamprosate has pro-
ved be a promising drug (Pelc, 1977).
When compared with naltrexone, the long-term use of acamprosate with naltrexone in the acamprosate group resulted in ab-
stinence lasting for 12 months during which acamprosate was taken and beyond, while in the case of naltrexone, recidiving and a
break of abstinence occurred earlier. Both preparations were more successful than the placebo (Melchior J. A., J.M. Hoes, 1999).
According to B. Mason, in 14 out of 16 studies conducted in different European countries it was found out that patients de-
pendent on alcohol and treated with acamprosate showed significantly better results in terms of the time to the first drink, ab-
stinence score, and cumulative abstination time than patients treated with the placebo (Mason, 2000).

CONCLUSION
The discovery of new preparations that can help to treat the alcohol dependence syndrome is not just a good motivation
for patients to abstinate, but also for doctors themselves to widen their knowledge of the possibilities of treatment.
It is not just about simple offering of a tablet to the patient that will help him/her to get rid of his/her problems, but com-
plex treatment, in which each new substance, verified in double- blind, placebo controlled perspective studies, should also be
proved by the doctors personal experience.
The experience we have presented in our work is not absolute, but it assesses the way though which we have tried to help
the patient in the best possible way.
In this process, the anti-craving substance acamprosate has been of substantial help.

LITERATURE
Bankole A. Johnson, Nassima Ait- Daoud: Neuropharmacological Treatments for Alcoholism: scientific basis and clinical fin-
dings, 2000, psychopharmacology, 149, 327-344
Besson J, Aeby F., Kasa A., Lehert P., Potgieter A.: Combined Efficacy of Acamprosate and Disulfiram in the Treatment of
Alcoholism: a controlled study. Alcohol Clin. Res., 1998, 22: 573-579
Dahchour A., Witte P. De: Ethanol and Aminoacids in the Central Nervous System: assessment of the pharmacological acti-
ons of acamprosate, 2000, Neurobiology, 60, 343-362
urik V., About the Role of the Ecology and Psychology on the Threshold of a New Millennium. In: Reforma psychiatrickej
starostlivosti, eskoslovensk konferencia, 19. - 21. april, 2001, Michalovce
Ehlers Cl.,Li TK, Lumeng L , HwangBH, Somes C, Jimenes P., Mathe AA/1998/Neuropeptid Y Levels in Ethanol in Naive Alcohol-
Preferring and Non-Preferring rats and in Wistar Rats after Ethanol Exposure. Alcohol Clin. Exp res. 22: 1778-82
Evens M: Tiapridal and Alcoholic Detoxification/authors transla./Acta Psychiatr. Belg, 1980.80: 149-155
ICD-10 Klasifikacija mentalnih poremeaja i poremeaja ponaanja, Kliniki opisi i dijagnostika uputstva, WHO, 1992, Beograd,
327: 65-78
Ignjatovi M., Ignjatoviov D., Krizov obdobia v liebe syndrmu zvislosti od alkoholu na psychiatrickej ambulancii,
Zdravotnicke noviny, ZdN .5, febr. 2001, in annex Lekrske listy, 1-8: 5
Kolib E. Priruka klinickej psychiatric, ASKLEPIOS, 1996, 7-240, 95 118
Kunda S: Klinika alkoholizmu, 1998, Osveta, 5-248
Lesch Otto M., Walter H.. Subtypes of Alcoholism and Their Role in Therapy, Alcohol and Alcoholism, 1996, Vo1.31: Suppl.1,
p. 63-67
Lovinger D M., High Ethanol Sensitivity of` Recombinant AMPA-type Glutamate Receptors Expressed in Mammalian Cells,
1993, neurosci Lett, 159, 83-87
Mason BJ, Ownby LR: Acamprosate for the Treatment of Alcohol Dependence: A review of Double-Blind , Placebo-Controlled
Trials, Feb. 2000., CNS SPECTRUMS, Vol. 5, No2
Mason B.J., Goodman A.M.: Cognitive Effects of Naltrexone and Acamprosate Administered Alone and in Combination, pre-
sented in: Annual meeting or the Research Society on Alcoholism /RSA/June 27-July 1, 1999/Santa Barbara, California/
Melchior J.A., J.M. Hoes: Relapse Preventions in Alcoholics, A review of Acamprosate versus Naltrexone, 1999, Clin. Drug
Invest., 17/3/, 211-216

13
 Monografia. Campral v liebe alkoholizmu, 1999, Farmakologick a klinicky prehlad, GROUP LIPHA, 7-6
Naranjo CA, Sellers EM, Sullivan JT, Woodley DV, Kadlec K., Sykora K. /1987/Serotonin Uptake Inhibitor Citalopram Attenuates
Ethanol Intake. Clin. Pharmacolog. Ther 41: 266-274
Naranjo CA, Kadlec KE, Sanhueza P, Woodley - :Remus D, Sellers EM/1990/: Fluoxetine Differentially Alters Alcohol Intake
and Other Consumatory Behaviors in Problem Drinkers, Clin. Phamracol. Ther 47: 490-498
Naranjo CA., Poulos C.X., Bremner KE, Lanctot KL/I992/Citalopram Decreases Desirability, Liking, and Consumption of Alcohol
in Alcohol-Dependent Drinkers, Clin. Pharmacol. Ther, 51: 729-739
Pelc Verbank P, Le Bon P, Gavrilovi M, Lion K, LehertP/1997/Efficacy and Safety of Acamprosate in the Treatment of Detoxified
Alcohol-Dependent Patients, Br J Psychiatry, 171: 73-77
Rush CR, Pazzaglia PJ/1998/Pretreatment with lsradipine, a Calcim-channel Blocker, Does not Attenuate the Acute Behavioral
Effects of Ethanol in Humans. Alcohol Clin. Exp Res22: 539-547
Smolik P: Duevni a behaviorlni poruchy MAXDORF , JESENIUS, 1996, 9-487, 112- 131
Suchopr J.: REMED1A, COMPENDIUM, 3. vydanie, PANAX, 1999, 1 743: 251-252
Swift RM: Drug Therapy for Alcohol Dependence, 1999, The New England Journal of Medicine, 1482-1489
Wilde MI, Wagstaff AJ: Acamprosate A review of its Pharmacology and Clinical Potential in the Management of Alcohol
Dependence After Detoxification, Drugs, 1997, Jube, 53/6/, 1038-1053

TABLE I: OVERVIEW OF PATIENTS THAT USED ACAMPROSATE

Number of patients 23
Women 9
Men 14

TABLE 2: CHARACTERISTICS OF THE PERIOD OF DRINKING, DURATION OF ABSTINENCE,

DETOXIFICATION, AND BREAK OF ABSTINENCE

Average age in years 43 26 (27 - 59)

Average period of drinking in years 10.47 (2 - 39)
Average duration of abstinence in months 7.52 (5 weeks 10 months)
Detoxification before the start of the use of 10 patients
acamprosate at a psychiatric ward
Detoxification before the start of the use of 13 patients
acamprosate at a psychiatric out-patient clinic
Break of abstinence within 3 months after the 3 patients
start of the use of acamprosate
Break of abstinence later than 3 months after 2 patients
the start of the use of acamprosate
Non-relapsing or recidiving patients 18 patients

TABLE 3: PSYCHIATRIC CO-MORBIDITY WITH F.10.25

DIAGNOSIS NUMBER OF PATIENTS

F.06 1
F.32 9
F.34.1 1
F.40.01 3
F.43 2
F.60 1
Without any other psychiatric co-morbidity 6

14
 TABLE 4: OVERVIEW OF PSYCHIATRIC PSYCHOPHARMACOMETRY

THERAPY: NUMBER OF PATIENTS: 23

ACAMPROSATE 5
ACAMPROSATE + FLUVOXAMINE 3
ACAMPROSATE + FLUOXETINE 1
ACAMPROSATE + CITALOPRAM 1
ACAMPROSATE + PAROXETINE 2
ACAMPROSATE + CLONAZEPAM 2
ACAMPROSATE + CITALOPRAM + CLONAZEPAM 7
ACAMPROSATE + PAROXETINE + CLONAZEPAM 2

TABLE 5: OVERVIEW OF ADVERSE EFFECTS OF ACAMPROSATE BY SYSTEMS

YES NO
GASTROINTESTINAL SYSTEM/NAUSEA, DIARRHOEA, ABDOMINAL PAIN/ 1 0
DERMATOLOGICAL/RASH, PRURITUS/ 1 0
MUSCLE SYSTEM /PAIN IN LIMBS / 1 0
NEUROLOGICAL 0 0
GENITOURINARY SYSTEM/IMPOTENCE 1 0
CARDIOPULMONARY SYSTEM 0 0
TIREDNESS 0 0
INCREASED TASTE FOR SWEET THINGS 10 0
INCREASED OR DECREASED BODY WEIGHT 0 0
TOTAL: 14* 0
* NONE OF THE 14 PATIENTS WHO SHOWED THE SPECIFIED ADVERSE EFFECTS INTERRUPTED THEIR TREATMENT WITH
ACAMPROSATE

15
OUTPATIENT PSYCHIATRIST ACTIVITIES OF CONSULTATIONS IN
DIAGNOSTING PROCESS AND TREATMENT OF PSYCHOSOMATIC
DISORDERS

AUTHORS
MUDr.Milan Ignjatovi, Psychiatric Medical 0ffice, Health Care Center, Bansk Bystrica
MUDr. Dana Ignjatoviov, Psychiatric Department, F. D. Roosevelts Hospital, Bansk Bystrica

SUMMARY
65 patients, 47 females and 18 males aged from 18 to 72 years were treated within consultations on various departments of
hospital in Brezno.
The most frequent diagnosis for being hospitalized are: chronical vertebrogenous algic polytopic syndrom, hypertension,
chronical ischemic heart disease and others.
They were diagnosed ex-post in psychiatric medical office and the most frequent diagnosis were psychosomatic disorders.
Thereafter the psychiatric therapy had started according to psychiatric algorythm, the most frequent managed treatment
was sulpriridum with SSRIs and combination of benzodiazepins and another drugs.
The effectivenes of the treatment was evaluated by patients subjectivelly, while the condition of more than half of all pati-
ents improved.

KEY WORDS
Outpatient psychiatrist activities of consultation, psychosomatic diseases, sulpiridum, SSRI, benzodiazepins

INTRODUCTION
It was Freud who laid the basis of psychosomatic medicine, and in the fifties of the last century came its boom thanks to
Franz Alexander /1/. Majority of his researches were formed by psychosomatic disorders with apparatus lesion, which used to
be called psychosomatosis in that time /4/.
This increase of interest in the fifties of the last century helped to found special psychosomatic departments in some hos-
pitals. It also helped to develop psychosomatic medicine as an interdisciplinary one.
Many patients with this diagnosis stay permanently in the care of district GP, internal medicine doctor, neurologist and also
of surgeon and finally they need to visit psychiatrist, when their condition is already chronificated and refractory. The patients
come there with headaches, insomnia and tension. The psychic symptoms scale is very wide. There are psychic disorders with
or without somatisation but of non-organic base, psychosomatic disorders with apparatus lesion and other somatopsychic
symptoms /3/. The above quoted doctor continues in his article: The doctor makes diagnoses of disorders or diseases which
he thinks of. He confirmed by this sentence that the patients symptoms should not be evaluated separately but totally within
bio-psycho-social model.

METHOD AND GROUP OF PATIENTS

The group consisted of 65 patients chosen on the basis of 5 including criteria: 1. somatic diagnosis, 2. psychiatric diagno-
sis according to ICD 10 (mainly anxious in clinical picture, anxiously depressive syrnptomatology with or without somatisation,
disorders such as dissociative, somatoforrn and psychosomatic), 3. therapy before psychopharmacotherapy management, 4.
continuation in psychopharmakological treatment (mainly sulpiridum, citalopram, paroxetinum and cionazepainum treatment
monitoring), 5. patients subjective valuation of treatment.

OBSERVATION
The results are based on retrospective evaluation of patients medical records, where focus was on diagnosis of somatic and
psychiatric psychopharmacotherapy and patients evaluation of psychiatric treatment.
Monitoring and scoring of results were realised in psychiatric medical office from the February 1, 1999 to February 29, 2000.
We have chosen two casuistic cases for illustration.

CASUISTIC No. 1:
This patent was not included in the study because she has been taking sulpiridum, paroxetinum, clonazepamum for two ye-
ars of her treatment and patients included in the study were monitored only for period of one year. Since the patient subjecti-
vely feels good, we objectively assess that her condition has improved and we chose the patient as a casuistic case.
The patient is a 48 years old woman, single, with positive family history, father has undergone surgery 9 times, e. g. ileus,
prostate, during the patients treatment her father died. Mother is after ventricule resection and agranulocytosis, brother has
undergone ventricule resection.

16
 In her personal history: she vomited once, was treated by her GP without any success for three months. There are also me-
grimous headaches in her personal history as well as long-term management of alprazolarnum.
Social history: single, lives with her parents who she has to take care of, hard working and having troubles with her sick pa-
rents (patients father died subsequently). She complains on vertebral column pain, insomnia followed by tension in the ven-
tricule area. Last 3 months she had very bad headaches.
Fluvoxarninum 50 mg in 1 tablet in the evening. Alprazolamum 0,5 mg in 1 tablet in dose of 0,5 tablet in the morning - no
tablet in noon - 0,5 tablet in the evening was long-term managed and within the first revision sulpiridum 50 mg in 1 tablet in
dose of 1 tablet in the morning - no tablet at noon - 1 tablet in the evening had been added. After sulpiridum management the
condition of patient had improved, she continued treatment. Patients father died after 3 montits, the condition got worse,
she became to fail in her new work. We excluded alprazolamum and managed clonazepamum 0,5 mg in 1 tablet in the evening.
Fluvoxaminum was excluded and substituted by paroxetinum 20 mg in 1 tablet in the morning.
Since the patient changed the job and failed in the new one, the requirements were too high, and the charge was growing.
She gave a notice from work and is unemployed at the moment. Now she subjectively evaluates her health condition as good
and stabilised. Headaches aregone, ventricule is without symptoms. She does not mention any unacceptable effects of the the-
rapy. Sleeping has improved and internal tension is gone.
We chose this case as the patient is under sulpiridurn management without evident unacceptable effects, and with combi-
nation of another psychopharmatics. Current therapy is: sulpiridium 50 mg in 1 tablet in dose of no tablet in the morning, one
tablet at noon, no tablet in the evening, paroxetinum 20 mg in one tablet in dose of one tablet in the morning, no tablet at noon,
no tablet in the evening, clonazepamun 0,5 mg in one tablet at the night.
The patient is currently taking care of her very sick mother and keeps looking for a new job.

CASUISTIC No. 2:
72 years old patient; female, married, pensioner, long-term treated on:
I 25 chronical ischemic heart disease, algic form, hemodynamically. compensated
I 10. hypertension WHO II, stabilised
I 83 varixy of inferior extremities with the sign of chronical venous insufficiency
K 80 status post cholecystectomiam propter lithysiasis in 1990
K 83 postcholecystectomic syndrome
K 86 pancreatophaty
K 43 status post hemioplasticam in cicatricae post cholecystectomiam
M 54 vertebrogenous algic syndrom of cervical and thoracal vertebral column with vertigo
J 42 chronical bronchitis currently in remission
E 66 exogenous obesity
Z 88 personal allergy history on drugs and biological substances
The patient visited an internal medicine office very often last year. She was also frequently hospitalised, complaining on nau-
zea, vertigo, palpitation and epigastric sharp pains. The patient says that her condition improved after being hospitalised and ma-
naged infusion, and so she was released from the hospital and sent home. Hospitalisations were short-time and the psychiatrist
who had seen her before recommended the patient maprotilinum. This treatment was evaluated by the patient as insufficient.
The patient was sent to our psychiatric medicine office in December of last year and we could see that the gastrointestinal
symptoms with vegetative disorder were not treated adequate.
From the patients documentation brought by her we found out that there was not described family, personal or social
history in any of these documents. Family history showed us that mother died of kidney failure, her brother died of cerebral
failure and her sister is treated on hypertension. Going further in exploration we found out matrimonial problems of the pa-
tient with her husband, who often got drunk. Tension was subsequently occurring in the family. We re-evaluated patients tre-
atment whose therapy consisted of glyceroli trinitras, isradipinum, pancreatinum, cisapridum, hymecromonum, maprotilini
hydrochloridum. Since the patient was considered to have neurastenic syndrome with depressive symptomaticity, later on as
pseudoneurastenic syndrome, we made the final diagnosis as a psychosomatic disorder. We excluded maprotilinum and at first
recommended revaluation of the treatment by other drugs, reducing or eventually excluding of procineticum and enzyme the-
rapy. We managed sulpiridum 50 mg in 1 tablet in dose of 1 tablet in the morning - no tablet at noon - 1 tablet in the evening,
citalopramum 20 mg in 1 tablet in the morning and clonazepamum 0,5 mg in 1 tablet in dose of 1 tablet in the morning - no ta-
blet at noon - 1 tablet in the evening.
The patient was sent home and recommended examination the following week, as she was again ready to go home and expec-
ted to be hospitalised in the Internal Department. She accepted our assurance with disbelief and after one week came satisfi-
ed because in spite of existing family problems the gastrointestinal symptoms have gone, sleep was qualitative,anxiety lost its
intensity and vegetative symptoms receded,. The patient came twice for examination and she evaluates her condition as good.

RESULTS
There were 65 patients in the group, 18 males (27,69%) and 47 females (72,30%), see Table No. 1.
The average age of patients was 47,66 years, the youngest patient was 18 years old, the oldest was 72 years old. The average
age of symptoms onset was 43,30 years, see Table No. 2.

17
 The average duration of symptoms was 4,4 years, the longest duration was 22 years, the shortest one was 6 months, see
Table No. 3.
The average duration of treatment in the psychiatric medical office was 6,81 months, the longest duration was 15 months,
the shortest one was 2 months, see Table No. 4.
Thirty seven patients (56,92%) out of 65 still continue in the treatment and 27 patient do not continue the treatment (41,53%)
and one patient does not continue the treatment because of hospitalisation (1,53%), see Table No. 5.
The list of patients diagnosis before the treatment is shown in Table No. 6. We have chosen only one diagnosis, the main
one from the group of patients with several somatic diagnoses. The most frequent diagnosis was M 53 (vertebrogenous algic
syndrome) in 6 patients, I 11 (hypertension) in 6 patients, I 25 (chronic ischemic heart disease) in 4 patients and the others as
well. Thirteen patients were without previous diagnosis.
The list of diagnoses in the psychiatric medical office is given in Table No. 7. The most frequent diagnosis was F 45 (psychi-
cal and behavioural factors related to disorders or diseases classified elsewhere) in 31 patients, F 45 (somatoform disorders)
in 15 patients.
Patients followed up in the study were diagnosed and treated with sulpiridum, SSRI drugs (most frequently with citalopra-
mum and paroxetinum), benzodiazepins (clonazeoamum) either in monotherapy or in combination of noted drugs and other
psychotropic drugs. The list of therapy is in Table No.8.
The evaluation of treatment effectiveness was based on patients subjective evaluation, where 31 patients evaluated the-
ir condition as good (47,69%), 29 patients didnt evaluate their condition (44,61 %), 1 patient evaluated his condition as partly
improved, but the pain remained, 1 patient felt partial palliation, 2 patients evaluated their condition as partly improved and 1
patient didnt evaluate has condition as good, see Table No. 9.

DISCUSSION
Outgoing from previous classifications, new ICD 10 classification divided all psychosomatic disorders into 3 bigger groups
which are dissociative disorder (converse disorder, F 44), somatoform disorder (F 45) and psychical and behavioral factors re-
lated to disorders or diseases classified elsewhere (F 54).
In our work of consulting experts we mostly come across disorders classified under F 54 which F. Alexander understood as
psychosomatic disorders with apparatus lesion and he used to call them psychosomatosis. We come across somatoform dis-
orders and dissociative disorders in smaller amount as well.
There are various names of factors that can lead into this kind of disorder in different studies. Some authors mention bio-
graphical factors for psychosomatic disorders uprise (4) which are listed in ICD 10 as Z codes (7). Another authors agree but
in different way- there isa psychic conflict in pathogenesis of somatic symptoms. The conflict undergoes a process ofsomati-
sation and leads into ulcerous disease in some cases. The difficulties are dependent on exacerbation of psychic conflict at the
beginning, dissociation of psychosomatic simultaneity may occur afterward (according to Mitscherlich) and so, some kind of
somatic autonomy occurs (3).
A long-way from one medical office to another is written in some patients history and treatment is long termed and com-
plicated in some point.
Sulpiridum is often recommended in psychopharmacotherapy, what is based on its biphasic effect. Specific neuropharma-
cological profile of sulpiridum is predominantly explained by sulpiridums blockade of especially D-2 dopaminergic receptors in
mesolimbic structures. By its selective bound on presynaptic dopaminergic receptors sulpiridum works as their agonist which
leads into greater liberation and turn over of dopamine. Sulpiridum has activating eftect in low doses (tymoanaleptic effect)
because of inhibition of dopamine secretion negative feedback, in higher dosage, it has neuroleptic effect which is atypical, es-
pecially antipsychotic without any significant influence on mobility (6).
Sulpiridum effectiveness on ventricular and duodenal ulceration is related to direct activity of bowel physiologic process.
Sulpiridum helps to set psychological stability when patient is under the influence of stress. This is the main reference in discu-
ssion about the topic of extensive tasks of sulpiridum in psychosomatic disorders broadly. Diagnosis such as megrim, asthma,
dermathosis, rheumatic diseases, urogenital diseases and cardiovascular diseases are arranged in that group (5).
Paunovi has the same opinion about the psychopharmacotherapy of those disorder, he adds ulcerous colitis, pruritus, in-
somnia and allergies to mentioned group (6).
Psychosomatic research also showed protective factors that protect people against uprise of psychogenous and psychoso-
matic disorder, e.g.: 1. long term and good attitude with at least one suitable person, 2. big family, compensatory unloading of
mother and others (4). Others put stress on the contact between patient and physician and mention in what the psychosoma-
tic attitude of physician is manifested in the practice: 1. Content of history, 2.
Method of history interview, 3. The way of minipsychotherapeutic conversations during control visits (3).
Of course, when appropriate diagnosis and well done management of treatment are made and adequate psychopharma-
cotherapy of e.g. sulpiridum is initiated, the adjuvant therapy of SSRI (8), benzodiazepins, tymoprofylactics and other drugs can
be considered. Resolution about the kind of psychopharmacotherapy is based on main and accessory symptoms. The clinical
picture is not simple very often as well and its consecutive treatment can be complicated. This could be covered depressions
(3), reactive depression with somatisation (5), where sulpiridum can exhibit the same effectiveness as oxazepamum and is more
effective than diazepamum and tianeptinum as well (5).
Options of psychotherapy are wide as well, like e.g. deeply oriented individual psychotherapy, KBT and especially Balints
groups that allow to get better view of attitude between physician and patient.

18
CONCLUSION
The problem of psychosomatic disorders is quite wide and interdisciplinary. Philosophical debates can lead into better and
more successful understanding of these disorders because human being actively affected the nature and disturbed a contract
with the nature from the beginning of his existence (2). Of course afterward, it was reflected in the relationship with ecological
and social factors that can be a predisposition for psychosomatic disorder uprise. The most complex model we should follow
in the process of diagnosis and treatment is bio-psycho- social model. We convicted ourselves about this fact very often in the
practice- our patients who were long term treated at other departments, missed basic information about family, personal and
social history and that is why it was difficult to understand symptoms repeating and frequent hospitalizations.
After biographical histories were discovered we successfully understood given patient, identified a diagnosis and managed
the therapy.
Thereby, psychiatrist activity of consultations represents important part of patients treatment who are hospitalized at other
departments. On the contrary, good history discover and diagnosis of somatic disorders that are made by other colleagues can
help us to solve these kind of patients quickly and successfully.

BIBLIOGRAPHY
Alexander F., Benedek Th., 1992: Psychosomatick medicina. Jej princpy a aplikcie, Psychosomatic Medicine, Its Principles
and Applications, W. W. Norton and Comp., New York, 1987, 1- 178
urk V., 1995: Etick aspekt interakcie spolonosti a prirody, Zbornik symposia ,, cta k ivotu, TU, Zvolen, s. 1- 113, 109
Gregor O., 1996: Psychosomatick pacient, Praktick Lka (Praha), 76, 1996, supp. 21-28, 14-15
Hatov M., Hato J., 1999: Klasifikcia psychosomatickch porch v ICD 10.
Porovnanie s klasickmi pojmami, Slovensk Lekr 4-5/99, 175-177
Johnson H and Johnson F.N., 1996: Sulpirid in neurotic, psychofunctional and affective
disorders associated with somatoform disorders, overview, Rev. Contemp.
Pharmacother., 1996, 7:299-312
Paunovi V. 1996: Sveske iz klinike psihofarmakologije, (Beograd), 330:96, 244-245
Smolk P., 1996: Duevn a behaviorln poruchy, MAXDORF (Praha), 7-504:48-50
vestka J. a kol., 1995: Psychofarmaka v klinick praxi, Avocenum (Praha), 249:93-96

Table No. 1 - The number of patients examined and consulted by psychiatrist

Absolute numbers Percentage

The number of patients 65 100

Table No. 2 - The age of patients and average age of difficulties beginning

Males 18 27,69
Females 47 72,30
The average age of patients 47,66 years
The oldest patient 72 years
The youngest patient 18 years
The average age of difficulties beginning 43,30 years

Table No. 3 - Duration of difficulties

The average duration of difficulties 4,4 years

The longest duration of difficulties 22 years
The shortest duration of difficulties 6 months

Table No. 4 - Duration of treatment in psychiatric medicine office

The average duration of treatment 6,81 months

The longest duration of treatment 15 months
The shortest duration of treatment 2 months

19
 Table No. 5 - Continuation in psychiatric treatment

Absolute numbers Percentage

Continued in treatment 37 56,92
Did not continued in treatment 27 41,53
Hospitalized 1 1,53
Total 65 100

Table No. 6 - Diagnosis before attending the psychiatric medical office

Diagnosis, ICID 10 The number of patients Diagnosis in words

B 49 1 Non-specified mycosis
C 53 1 Uterus malignance
D 34 1 Thyroid benignance
E 03 1 Other hypothyreosis
E 04 2 Other non-toxical Derbyshire neck
E 11 1 Noninsulindepedent DM
E 28 1 Functional disorders of ovaries
F 48 2 Other neurotical disorders
G 40 2 Epilepsy
G 43 1 Megrim
G 45 1 Transtory ischemic attacs and related syndroms
G 50 1 Neuralagy of n. trigeminus
G 61 1 Inflammatory polyneuropathy
G 99 1 Other NS disorders by diseases classified elsewhere
I 11 6 Hypertension
I 25 4 Chronical ischemic heart disease
I 51 2 Cardiovascular diseases and vaguely described heart diseases
I 83 1 Varixy of inferior extremitatis
J 30 1 Vasomotoric and allergic coryza
J 45 3 Asthma
K 25 2 Ulcus ventriculi
K 35 1 Appendicitis acuta, st. post APE
K 51 1 Ulcerous colitis
H 16 1 Coxarthrosis
M 53 6 Vertebrogenous algic syndrome
M 54 3 Dorsalghia
M 82 1 Ostheophorosis
N 18 1 Chronical kidney failure
R 10 1 Abdominal pain and per-menstruation syndrome
Z 88 1 Personal allergy history on drugs and biological substances
No diagnosis 13 -
Total 65 -

20
 Table No. 7 Survey of diagnosis in psychiatric medical office

ICD 10 diagnosis Absolute numbers Percentage

F 06 6 9,23
F 19 1 1,53
F 40 7 10,76
F 41 1 1,53
F 43 1 1,53
F 44 2 3,07
F 45 15 23,07
F 54 31 47,69
F 61 1 1,53
Total 65 100

Table No. 8 --- Survey of theraphy in psychiatric medical office

Generic name of the medicament Number of patients

Sulpiridum 2
Paroxetinum 2
Tianeptimum natricum 1
Fluoxetinum 1
Sulpiridum + citalopramum 5
Sulpiridum + clonazepamum 7
Sulpiridum + other medicament 1
Sulpiridum + other SSRI 5
Citalopramum + clonazepamum 1
Paroxetinum + clonazepamum 1
Tianeptimum natricum + clonazepamum 1
Dibenzepini hydrochloridum + clonazepamum 1
Sertralinum + alprazolamum 1
Oxazepamum + prochlorineperazinum 1
Sulpiridum + citalopramum + clonazepamum 8
Sulpiridum + paroxetinum + clonazepamum 9
Citalopramum + clonazepamum + other medicament 1
Sulpiridum + clonazepamum + other medicament 5
Sulpiridum + citalopramum + other medicament 3
Sulpiridum + 2 other medicaments 1
Sulpiridum + paroxetinum + acidum valprocium, natrii 2
valproas
Sulpiridum + citalopramum + clonazepamum + acidum 1
valprocium, natrii valproas
Sulpiridum + clonazepamum + natrii valproas + 1
carbamazepinum
Risperidonum + sertralinum 2
Risperidonum + sertralinum + clonazepamum 1
Risperidonum + tianeptimum natricum + 1
bromazepamum
Total 65

21
 Table No.9 Subjective evaluation of treatment

Absolute numbers Percentage

Partly improved condition but pain chronicity 1 1,53
Partly relief 1 1,53
Condition is improved 2 3.07
Condition is good 31 47,69
Non-valuation of condition 29 44,61
Treatment was not good 1 1,53
Total 65 100

22
POSSIBLE ADVERSE EFFECTS IN THE TREATMENT OF AGORAPHOBIA
WITH VALPROIC ACID AND NATRIUM VALPROATE- OUR ONE YEAR
EXPERIENCES

AUTHORS
MUDr. Milan Ignjatovit 1
MUDr. Dana Ignjatoviov 2
MUDr. Jasmina Jankovi- Gaji 3
Psychiatric medical office, Health Care Center, Bansk Bystrica, Slovak Republik
Psychiatric medical office, Heaith. Care Center, Bansk Bystrica, Slovak Republik
Psychiatric medical office, KBC D. Mikovi, Beograd, Yugoslavia

SUMMARY
Valproic acid and natrium valproate have accurately defined diagnostic area in psychiatry which are mostly affective disor-
ders. Their indication was enlarged latterly by panic disorder which hasnt responded to the conventional therapy.
Patients with panic disorder have tried different kinds of drugs very often and there were diagnosis such as polytopic verte-
brogenous algic syndrome, epilepsy, megrim, vertigo and others in their medical history. Within these kinds of diagnosis, they
were given different kinds of drugs that could mutually interact. The main goal of the study was to verify if there is a hepato-
toxic effect after one-year management of valproic acid and natrium valproate combination.
We checked the hepatotoxicity by common biochemical parameters which are available at psychiatric medical office
(Bilirubin, ALT, AST, GMT, ALP) without the assessment of serum level of managed drugs. Noted biochemical parameters were
assessed before the treatment of valproic acid and natrium valproate, and then one month, six months and twelve months af-
ter the treatment.
The treatment was assessed retrospectively during the period of time of one year from March 1, 2000 to March 31, 2001
in the group of 9 patients (women N= 8) at the psychiatric medical office of the first author. The average age of patients was
47,77 years.
The results of this study show that although there was mild elevation of enzymes (aminotransferases) after the manage-
ment of valproic acid and natrium valproate, these levels didnt exceed the physiological levels.

KEY WORDS
Panic disorder, valproic acid, natrium valproate, possible adverse drug effects concerning
Hepatotoxicity

INTRODUCTION
Valproic acid and natrium valproate are used in psychiatric patients for their antidepressive (Calabrese J.R., 1993, Swann
A.C., 1997) antimanic (Pope H.G., 1991, Bowden Ch.L., 1994, McElroy S.L., 1996) and antiagressive effect (eventually in persona-
lity disorders) as well as in cases of pharmacoresistance to others antidepressive drugs, such as lithium (Pope H.G., 1991) and
karbamazepinum. It is used successfully with patients with short cycling (vestka J., 1995, Calabrese J.R., 1993, Bowden Ch.L.,
1994). Besides, its usage is recommended in cases of anxious disorders, especially in case of panic disorder with no respond to
conventional therapy (Baetz M., 1998).
There are different theories on panic attack origin; serotonin theory is one of them. Even though all the theories are not
expressly confirmed in clinical practice (Charney D.S., 1986). There are speculations about connection between attack affecti-
ons (narcolepsy, epilepsy) and panic disorder in domestic scientific area. Comorbidity of panic disorder with various affections
(mitral valve prolapses, asthma, depression) is listed. There is another hypothesis on the connection between panic disorder
and megrim based on serotonin neurotransmitter system dysfunction (Kukumberg P., 1999).
The usage of natrium lactate for panic attack induction is known in experiments. There are experiments of usage of valpro-
ate as an anticonvulsive drug for panic attacks (antipanic effect). There are several reasons for that:
it improves GABA activity in brain
it has anxiolitic effect in animal experiments
it was reported as an effective drug in case of panic attack in some preliminary studies but it has not been systematically
assessed in prevention of panic attack inducted by natrium lactate (Keck P.E., J., 1993).
There is comorbidity and consequently polyprogrnasy seen in the case of panic disorder at the psychiatric medical office
very often. In consideration of possible interactions between managed drugs the development of functional or morphological
apparatus damage that participate on drug biotransformation is possible as well (Majki- Singh N., 1993), including apparatuses
that dont directly participate on drug biotransformation (e.g. polycystic ovarian syndrome in women with epilepsy). Direct
contingency between management of sodium valproate and polycystic ovarian syndrome has not been proved in this trial; more
prospective trials must be realized (Duncan S., 1998).

23
 The apparatus that is directly involved in drug biotransformation is liver and its function can be impaired by the manage-
ment of these drugs. (Jiminez - Rodriguezvila, 1995).
The hepatotoxicity is manifested by biochemical as well as by morphological changes of liver tissue. The most frequent chan-
ges are elevation of ALT and AST (Krika M., 2000). We know from various bibliografical sources that there are more than 200
different clinical- chemical methods which are used for liver impairment testing.
Liver is the greatest gland in the body and it is used as the central metabolic apparatus. The first diagnostic step of appa-
ratus damage confirmation is detection of enzymes and their izoenzyrnes in the serum. Hepatitis caused by drugs and other
chemical substances is known as toxic hepatitis.
Liver is the main location of drug metabolism and hepatocellular effects caused by the drugs are regarded as direct toxic
effects (predictable, direct hepatotoxic) and Flosyncratic (unpredictable, hepatitis alike). (Majki- Singh N., 1993).

THE GOALS OF THE STUDY

The main goal of the study was to follow up possible biochemical parametens changes that should suggest drug hepato-
toxicity. The parameters were checked before management of valproic acid and sodium valproate, after one month of the ma-
nagement, after 12 months and after 1 year of noted drug management with combination of other psychotropic drugs. We have
followed up the level of cumulative Bilirubin, AST, ALT ALP, GMT.

SET AND METHODICS

We have retrieved patients who suffer from agoraphobia with panic disorder that is resistant to conventional psychophar-
macotherapy in the cardfile of psychiatric medical office of the first author. Noted mental disorder has been diagnosed accor-
ding to DSM IV classification (Kaplan et al., 1994) and MKCH - 10 classification. Patients with psychiatric comorbidity were exclu-
ded from the observation.
The overall amount of evaluated patients reached the level of 9, one from the group was male. The average age of the gro-
up members was 47,77 years (at the interval from 21 to 57), the patients were monitored in the psychiatric medical office of the
first author during the interval of one year from the March 1, 2000 to March 31, 2001.In the treatment of all patients valproic
acid and sodium valproate with combination of other psychotropic drugs in all cases were used.
The treatment of patients and possible hepatotoxicity were observed during the interval of one year. No patient noted any
adverse effects of valproic acid and sodium valproate (e.g. gastrointestinal system, headache, somnolence and others).
Clinical status (condition) of all 9 patients has markedly improved (no panic attacks, no agoraphobic behavior nor anticipa-
te anxiety) and has been subjectively evaluated by patients as good.
We have followed up biochemical parameters which indicate possible hepatotoxicity before the management of valproic
acid and sodium valproate with combination of other psychotropic drugs and after noted management.
The study has not been submitted to the ethic committee for approval because the study was the retrospective evaluation
of medical documentation.

RESULTS
The results are stated in Table No. 1 and Table No. 2.
Whereas these were cases of resistant statuses of agoraphobia with panic disorder, valproic acid and sodium valproate in
combination with other psychotropic drugs were used in the treatment of all 9 patients. Valproic acid and sodium valproate
were used in cases of:
2 patients who received SSRI with high potent benzodiazepin
4 patients who received SSR1 with neuroleptic drug and benzodiazepin
1 patient who received SSRI with TCA and benzodiazepin
1 patient who received SSRI with TCA, benzodiazepin and neuroleptic drug
and 1 patient who received SSRI with benzodiazepin and tymoprophylactic drug
From the group of SSRI 6 patient received paroxetinum, 2 patients received sertralinum and 1 patient received citalopra-
mum. 9 patients received clonazepamum, 1 patient received suipiridum, 1 patient received haloperidolum, 1 patient received
prochlorperazinum and 2 patients received risperidon. One patient received maprotilinum, 1 patient received dosulepinurn with
combination of SSRI, high potent benzodiazepin, valproic acid and sodium valproate. 1 patient received carbamazepinum with
combination of SSRI, high potent benzodiazepin, valproic acid and sodium valproate.
We followed up biochemical parameters which suggest possible hepatotoxicity. We didnt find any abnormality in previously
noted data in any of our patient in the interval of one year combined therapy of valproic acid and sodium valproate. Changes
of biochemical parameters were in the interval of normal levels.

DISCUSSION
Liver - our the greatest biochemical factory processes huge amount of chemical substances and drugs. Drugs and chemical
substances which can lead to hepatocellular impairment depending to their dose belong to the group of direct hepatotoxins.
Clinical picture is variable and depends on the origin and dose of toxin. If the management of drug is excluded, liver comple-
tely restitutes.

24
 Idiosyncratic, hepatitis alike reactions can occur after the management of e.g. MAP inhibitors, antituberculotic drugs, sul-
fonamides, metyldopa, after halotane anesthesia (Majki- Singh N., 1993).In the treatment of agoraphobia with panic disorder
antidepressive drugs of the SSRI group are mostly used (Prako J., 1995) and possible interactions between this group of drugs
and other drugs are hypothetical in most cases.
The process of metabolism runs through izoenzymes. This substances react as substrates, inductors or inhibitors of other
drugs metabolism in noted pathway (vestka J., 1998).
Sodium valproate should be inhibitor of CYP 450, it inhibits SSRI metabolism what can also influence their metabolism. That
in clinical practice means possible adverse effects uprise that can be severe in some cases (vestka J., 1998).
Biotransformation of sodium valproate runs through CYP 2C19. The majority of SSRI is CYP 450 inhibitor and their biotran-
sformation runs through different CYP 450 (e.g. CYP 2D6 metabolize paroxetinum).
Moreover, drugs can be hepatotoxic and various liver tissue impairment can cause changes in serum enzymes levels.
According to internationally accepted nomenclature, liver impairment is classified as hepatocellular (acute and chronic he-
patitis and cirrhosis), cholestatic (e.g. obstructive disease of biliary tract) neoplastic and infitrative diseases.
Serum enzymatic profiles present in cases of drug inducted liver impairment vary a lot and imitate practically each kind of
liver disease.
That is why it is very difficult to detect and classify the manifestation that was caused by some kind of drug.
To simplify the diagnostic process, the following rules were made:
activity of GMT is unequally elevated and 3 factors are excluded - alcohol, obstruction of biliary trot and invasive processes
of liver
normal GMT activity, other enzymes are elevated (AST, ALT, ALP...)
cholinestherasis activity quickly droops or is the only one that is low
if liver enzymes activities are pathological in serum and histopathological picture is normal (Majki- Sinhg N., 1993).
Hepatotoxicity can be manifested by elevation of ALT, AST (Krika M., 2000). At the same time the author notices that the
elevation of ALP is important as well and depression of albumin is more serious because from the view of possible developing
liver lesion the diagnosis is more severe. In the study where 1172 epileptic patients received slowly soluble valproate (Bergmann
A., 1999) as monotherapy or in combined therapy with other antiepileptic drugs or other drugs was fond that valproate is well
tolerated and effective in all types of epileptic seizures in monotherapy management and polytharapy management as well.
We didnt find such voluminous studies on valproic acid and sodium valproate in psychiatry relative to agoraphobia with panic
disorder nor the studies on their hepatotoxic influence. The usage of valproate in cases of resistant panic disorders (Baetz M.,
1998) and management of valproate in cases of sodium lactate inducted panic attacks was published (Keck P.E., 1993).
Whereas these were resistant types of disorders valproate was not managed in monotherapy but in combination with SSRI,
TCA, high potent benzodiazepin, neuroleptic drugs and tymoprofylactic drug in all patients in our study.
We didnt find changes in biochemical parameters besides their drift in the interval of physiological levels. From the previo-
usly stated data about possible hepatotoxic effects we didnt find abnormalities, which should confirm hepatotoxic effects in
the group of our patients who received valproate in combined therapy during one-year interval.
Our study has the following shortcomings:
low number of patients
polytherapy
impossibility to evaluate serum level of managed drugs according to unavailable laboratory tests
subjective evaluation of patients condition improvement without aggregate scales of appraisal

CONCLUSION
Even though valproate is more frequently used in neurology, its usage is effective in the treatment of resistant agorapho-
bia with panic disorder in psychiatry.
We found valproate as well tolerated, effective and without any adverse effects connected to possible hepatotoxicity during
its management in cases of agoraphobia with panic disorder resistant to conventional therapy.

BIBLIOGRAPHY
Baetz M., Rudradeo C. Bowen, FRCPC, Efficacy of Divalproex Sodiumin Patients with Panic Disorder and Mood Instability
Who Have Not Responded to Conventional Therapy, Can J Psychiatry, Vol. 43, February 1998, 43: 73- 77
Bergmann A., Schmidt P., Hutt H-j, Elger C.E., Epilepsy Treatment with a Sustained- Release 2.
Bowen L. Ch., Brruger A., Swann A.C., Efficacy of Divalproex vs Lithium and Placebo in the Treatment of Mania. Journal of
the American Association, march 23- 30, 1994, Volume 271
Calabrese J.R., Woyshvilli M.J., Kimmel S.E., Rapport D.J., Predictors of Valproate response in Bipolar Rapid Cycling, Journal
of Clinical Psychopharmacology, 1993, Vol. 13, No 4, 280- 283
Chaney D.S., Heninger G.R., Serotonin Function in Panic Disorder, Arch gen Psychiatry, 1986, 43: 1059- 1065
Duncan S., Polycystic Ovarian Syndrome in Women with Epilepsy, Aspects of Epilepsy, 9, Oct., 1998, 1- 5
Jiminez- Rodriguezvila M., Caro- Paton A., Conde M et al: Side effects of sodium valproate, mainly related to its hepatic and
pancreatic toxicity, Int J Clin Pharm Res 6, 1986, 217- 224
Keck P.E. Jr, Taylor V.E., Tugrul K.C., McElroy S.L., and Bennett J.A.: Valproate Treatment of Panic Disorders and Lactate-
Induced Panic Attacks, Biol. Psychiatry, 1993, 33: 542- 546

25
 Pako J., Agorafobie In Raboch J. ed. Psychiatrie. Doporuen postupy psychiatrick pe. Praha: esk psychiatrick spo-
lenost, Galn, 1991, 41- 61
Kukumberg P., Panick porucha a migrna, es. a Slov. Neurol. Neurochir., 62/ 95, 1999, No 1, p. 57- 59
Krika M a kol., Rizoko liekov v medicnskej praxi, Slovak Academic Press, 2000, Bratislava, 474: 307
Majki- Singh N., Klini6ka enzimilogija, Univerzitet u Beogradu, Farmaceutski fakultet Zavod za Medicinsku Biohemiju, Kliniki
Centar Srbije,. Institut za Medicinsku Biohemiju, Beograd, 1993, 875: 225, 257, 269, 272, 273
McElroy S.L.,Keck P.E., Stanton S.P., Turgul K.C., Bennett J.A., Strakowski S.M: A Randomized. Comparison of Divalproex
Oral loading Versus Haloperidol in the Initial Treatment of Acute Psychotic Mania, J Clin Psychiatry 1996, 57: 142- 146Pope H.G.,
McElroy S.L., Keck P.E., Hudson J.I: Valproate in the treatment of Acute Mania, arch. Gen Psychiatry- Vol 48, january 1991
Swann A.C., Bowen Ch.L., morris D., Calabrese J.R., Petty F., Small J., Dilsaver S.C., Davis J.M> Depression During Mania, Arch.
Gen Psychiatry, Vol 54, January 1997
vestka J. a kol., Psychofarmak v klinick praxi, Grada Publishing, 1995, 241, 117
vestka J.: SSRI lky prv volby, MAXDORF JESSENIUS 1998, 153: 83, 93

TABLE NO.1 - AVERAGE LEVELS OF IOCHEMICAL PARAMETERS TESTED IN PSYCHIATRIC MEDICAL OFFICE
DURING ONE YEAR INTERVAL

0 month 1st month 6th month 12th month Physiol-ogical

level
AST 0,13 0,22 0,29 0,28 0,0-0,65
ALT 0,16 0,36 0,30 0,33 0,0-0,7
ALP 1,46 1,23 1,47 1,43 0,57-1,57
GMT 0,36 0,34 0,36 0,34 0,17-1,12
Prote-ins total 8,93 8,24 7,33 8,26 5,0-20,5

TABLE NO. 2 - LIST OF PSYCHOPHARMACOLOGIC MANAGEMENT

SSRI* SSRI SSRI SSRI SSRI

BD** NL*** TCA*** TCA BD
BD BD BD tymopofyl-active drug****
NL
val-proic 2 4 1 1 1
acid*
sodium
valp-roate

* 6 patients received paroxetinum, 2 patient sertralinum, 1 patient citalopramum

** BD = high potent benzodiazepin- clonazepamum which was received by 9 patients
*** NL = sulpiridum 1 patient, haloperidolum 1 patient, prochlorperazinum 1 patient,
risperidon 2 patients
**** TCA = maprotilinum I patient, dosulepinum 1 patient
**** tymoprofilactive drug = carbamazepinum 1 patient

26
THE EFFICACY OF DEPRESSION TREATMENT WITH MILNACIPRAN
(A SIX- MONTH EXPERIENCE)

AUTHORS
Dana Ignjatoviov, M.D. (1)
Milan Ignjatovi, M.D. (2)
Silvia Beatriz Schweitzer, M.D. (3)

(1, 2) Private Psychiatric Outpatient Surgery, Cesta k nernocnici 1, Banska Bystrica, Slovak Republic
(3) Psychiatric Department, Cespedes, Buenos Aires, Argentina

Summary
Depression represents one of the most frequent and grave psychical alienations. It manifests itself by tiredness, sleeping
malfunction, headaches, loosing or putting on weight, and failure of sexual function. Bad mood, however, is not necessarily the
most dominant symptom G. N. Christodoulou, 2002]
It means that together with the establishment of the right diagnosis it is very important to manage an adequate treatment
of depression. Some of the key points, not only in the conditions of outpatient treatment, are anamnesis exploration of previo-
us depressive episodes, family anamnesis of affective diseases, and clinical exploration in relatives.
Depression today represents the 4th most frequent cause of health damage or loss of life due to early affection or morta-
lity. It is expected that depression will become the 2nd in 2020 [G.N.Christodoulou, 2002].
In the U.S.A., yearlong prevalency represents 12.9% in women and 7.7% in men [Kessler et al., 1994). In Europe, prevalency
is 17% [Lepine et al., 1997].
Our 6-month follow-up included 12 patients using milnacipran 100 mg per day. We made evaluations of HAMID and HAMA
at the start (it means on the first day of the follow-up) and used the CGI scale. Two patients were discarded from our follow-
up: one patient had discontinued the medication on her own in the 4th month of the course of treatment and the other one
was hospitalized due to a high risk of suicidal tendencies (HAMD-39 points, HAMA-28 points).
We have evaluated HAMD on the first day of treatment, then one month later, and then half a year after the setting up of
milnacipran 100-mg per day. In the 2nd month we did not observe any kind of strong amelioration (HAMD-19.8 points), but in
the 6th month HAMD reached to 7.1 points.

Key words
Depression, HDRS (Hamilton Depression Rating Scale), CGI (Clinical Global Impression), milnacipran
Introduction
The development of new antidepressive drugs in last fifty years has come through the complicated way which was started
by the antidepressive effects discovery of iproniazid (an antituberculotic agent) in 1950 and imipramine (an antihistamine) in
1955 [David J. Nutt, 2002]. The progress has finally resulted in the present very effective and strongly selective antidepressive
medicaments accompanied by a minimum of undesirable effects - venlafaxin, milnacipran [S.M. Stahl, 1997].
Tricyclic antidepressives (TCA) are strongly effective, especially in the treatment of harder depressions [P. Boyer and M.
Briley, 1998, S. A. Montgomery, 1999], but they are characterized by a large number of undesirable effects. At the same time, it
must be said that SSRI have at least the same efficacy as TCA [J. vestka, 1998].
SSR1 are safer and better accepted by the patient. Nevertheless, they are not so effective for grave depressions [M. Briley,
1997], but they have their own exceptional position in the treatment of depressions, especially those connected with anxiety.
SNRI antidepressives are more effective compared with the effect of placebo in a big depression episode treatment [Y.
Lecsubier, 1997] and have the same effect as TCA, but theyare much better accepted by the patient [Kasper, 1996].
The effect of SNRI in comparison with SSRI is almost on the same level [P. Boyer and M. Briley, 1998, M. Briley, 1997], but
their dual effect on noradrenergical and serotoninergical neurotransmission foreshadows higher effectiveness than in SSRI.
Thanks to this fact, SNRI have become very promising antidepressants [P. Boyer and M. Briley, 1998].
Depression represents a heterogeneous unit with a different variety of forms. It ranges from a light depressive episode,
through dysthymia to grave depression, which requires hospitalization [S.A. Montgomery, 2001].
Symptoms of depression change according to the functional activity of the neurotransmitter system. Considering this, we
can divide the symptoms of depression into two groups. The first one is serotoninergic and the second one is noradrenergic. It
corresponds generally with the concept of impulsiveness, aggressivity, lower sexual appetence (5-HT system), and lack of mo-
tivation and energy (NA system), or when mixed, with anxiety, irritability, bad humour, and failure of cognitive functions [S.A.
Montgomery, 2001].
It means that antidepressives with a dual effect (venlafaxin, milnacipran) show a theoretical promise to suppress, by their
dual effect, the symptoms of depression. The catecholaminal hypothesis [Schmidtkraut and Kety, 1967] assumes that depressi-
on results from an insufficient activity of central noradrenergic neurons, whereas the indolaminal hypothesis [Van Praag, 1982]
talks about a deficit of the activity of central serotoninergic neurons [Moret, 1985].

27
 Milnacipran is a new antidepressant inhibiting the reuptake of serotonin and noradrenaline in vitro and in vivo without an
effect on the reuptake of dopamine. Microdialyses confirmed a higher extracellular level of serotonin and noradrenaline.
Milnacipran does not show any evidence of interaction with known neurotransmitter receptors.
In comparison with TCA, chronic milnacipran administration does not modify the linkage to beta-adrenoreceptoral sites or
the function of the second messengers [P. Boyer and M. Briley, 1998].
Observed group and methodology
The group under observation included 12 patients. Women (n = 8, average age = 41.33 years, age interval, 22y-60 years). Two
female patients were rejected out of the follow-up. One has discontinued the treatment at her own request (but not due to
undesirable effects) and the second one was hospitalized (HAM:D-39 points, HAMA-28 points).
We have made HAMD and HAMA evaluations on the first day, then after one month and then in the sixth month of the follow-
up. We have evaluated CGI, too. All patients took milnacipran in a dose of 100 mg per day.
Criteria for insertion:
age 18 - 60 years
MKCH-10 and DSM-IV diagnostic criteria for an intermediately grave (F.32. I) to a grave episode of depression without
psychotic symptoms (F.32.2)
HAMD up to 18 points
6 months follow-up
Criteria for rejection:
comorbidity together with other psychical diseases
organic psychical affects
mania, hypomania
dysthymia
schizophrenia, schizoaffective failures
alcoholism and other kinds of dependence
pregnancy
epilepsy in anamnesis
cardiac rhythm failures in anamnesis
important somatic diseases
A certain shortage of this study could be a small group of patients in whom we observed the clinical status and evaluated
HAMD and HAMA scales. But we did not make MADRS evaluation, which is frequently used in control studies.
Another shortage of this paper is the duration of the study. The follow-up lasted only for six months and we did not make
HAMD and MAHA evaluations in the third month. There were only three evaluations on the first day, after one month, and
on the last day of the follow-up.

Goals of study:
to compare the results of HAMD on the first day, after one month, and in the sixth month of the follow-up using milnaci-
pran in a dose of 100 mg pro die
to note any undesirable effect of milnacipran during a six months lasting follow-up

Results
We have included 12 patients into the follow-up, using the criteria of inclusion (Table 1). We used HAMD, HAMA (Table 2),
and CGI for the evaluation. We rejected two patients. The averageHAMD on the first day of the follow-up was 21.5 points, HAMA-
15.4 points. After one month, the average was HAMD-19.8 points (only 1.7 points amelioration) and HAMA-12.4 points. After a
six-month follow-up, it was HAMD-7.8 points (13.7 points amelioration) and HAMA-7. 1 points. Three of the 10 patients under
observation had already been treated for an episode of depression in the past. All of them used SSRI and anxiolytic agents.
In the patients we found the following undesirable effects: dryness in the mouth - 2 patients, dysuria - 3 patients, GIT trou-
bles - 1 patient (Table 3). For complex evaluation of treatment efficiency, we used CGI (Clinical Global Impression).

Discussion
Clinical studies are a suitable source of information about new preparations, but physicians have to verify their effect when
prescribing them to patients [S.A. Montogomery, 1999]. Noradrenergic and serotoninergic neurons take the most important
part in the mechanism of the effect of neurons. /S. Kasper, 2002/.
We can say that medicaments in which two or more synergic effects are combined together might have a higher therapeutic
effect and toleration comparable to the therapeutic mechanism of the effect of highly selective substances (S.M. Stahl, 1997).
Milnacipran is a cyclopropane derivative which inhibits noradrenergic and serotoninergic reuptake in the presynaptic area.
No activity of postsynaptic receptors was observed.
The most frequently used dose is 50 mg of milnacipran two times per day [C.M. Spencer and M. Wilde, 1998]. A dose of 100
mg of milnacipran pro die manifested a sufficient effect in our six-month follow up. Amelioration appears mostly in the second
week of therapy [Spencer and Wilde, 1998] with a daily dose of 100 mg (4 weeks - 3 months follow up). We observed not so
marked amelioration after one-month therapy (HAMD 1=21.5 points, HAMD2=19.8 points - 1.7 points difference).

28
 Milnacipran had an equal effect to those of imipramine and clotnipramine, 150 mg pro die in Japanese patients [Spencer
and Wilde, 1998]. Milnacipran was less effective than clomipramine in our 6 months study.
A comparison was carried out concerning the effects of milnacipran 50-100 mg and 20 mg fluoxetin pro die, 200mg flu-
voxamin pro die and rnianserin 30-60mg pro die in the 4th and 12th week. Milnacipran had the same effect on hard depression
as TCA and SSRI during the 4-12 week follow-up. Milnacipran was very well tolerated with a minimum of undesirable effects -
dysuria 7% [Spencer and Wilde, 1998].
According to the study of Kasper et al., 1996, one of the most frequent undesirable effects during milnacipran therapy is
dysuria (2.1%). Pending our follow-up of undesirable effects occurrence, dysuria appeared in three patients, dry mouth in two
patients, tremor in two patients, gastrointestinal troubles in one patient, and obstipation in one patient. These results are com-
parable with the international studies [Spencer and Wilde, 1998; Kasper, 1996].
The reported undesirable effects did not result in discontinuation of milnacipran therapy. A very important thing for the
effect comparison of medicines is comparative studies, multicentred and placebo-controlled.
In our study we focused on the results of a six-month milnacipran therapy course in ambulatory conditions but we did not
compare it with placebo and SSRI. It would be desirable to do it in the future.
Several studies were published in the United States which covered 527 ambulatory patients (131 patients used milnacipran
25mg pro die, 130 patients used milnacipran 50mg pro die, 133 patients milnacipran 100mg pro die, and placebo was used by
133 patients).
The follow-up included HAMD results with more than 22 points (average entering HAMD in our study was 21.5 points),
MADRS, and CGI. The results of milnacipran 100mg per day were significantly better than placebo (p < 0.01). There were about
64% responding patients pending 8 weeks follow-up with a milnacipran dose of 100 mg per day [Y. Lecrubier, 1997].
The follow-up included 68 patients with a milnacipran dose of 50mg in comparison with 49 patients treated with placebo
in Europe. HAMD was higher than 22 points --and according to the results the differences were not statistically significant. [Y.
Lecrubier, 1997].
A milnacipran dose of 50mg in 29 patients and placebo in 29 patient were compared in the third study. Together there were
58 hospitalized patients and after 4 weeks follow-up HAMD changed from 18.7 to 7.1.
We observed HAMD, which at the beginning of study was 21.5 points. After a month, HAMD became 19.8 points, which me-
ans only 1.7 points amelioration. At the end of the 6th month, HAMD was 7.8 points. Amelioration was thus 13.7 points compa-
red with the first of the follow-up.
We also evaluated global clinical impression. The grade of illness importance on the first day of the follow-up: intermediate
(6 patients), hard (4 patients). Grade of illness importance at the end of the 6th month was: normal, no evidence of illness (5
patients), marginal evidence of illness(5 patients). Very clearly global amelioration appeared in all 10 patients.
During the four months lasting follow-up of patients with a milnacipran dose of 50mg per day, all patients were evaluated
as very clearly ameliorated [Rouillon, 2000]. Although a group of 10 patients is small, the results show that our experience is
comparable to the studies made in the US and Europe (France and Sweden), which demonstrate that new SNRI medicaments
specifically affecting serotonin and noradrenaline are more effective on hard depression than SSRI and possess the same effect
as TCA with a smaller number of undesirable effects {Briley, 1998].
Another six-month study made on a small group of 41 patients and comparing 100mg milnacipran to 75 mg clomipramine
showed a 50% reduction of HAMD. But there were no significant differences in MADRS and CGI scales [P. Boyer and M. Briley,
1998].
Many studies confirmed milnacipran effectiveness in the therapy of depression compared to other antidepressive agents
[Hndmarch,1997, Kasper, 1996, Spencer, 1996].
These published studies helped us to understand the theoretical basis of milnacipran role in hard depression episode tre-
atment which we verified in practice.
Conclusion
Depression is very a heterogeneous unit [S.A. Montgomery, 2001]. It has various manifestations requiring complex and
adequate antidepressive therapy.
Milnacipran exerts its effect on basic depression symptoms including anxiety, sleeping malfunction, and psychomotoric re-
tardation. It does not affect memory functions.
Milnacipran does not have any interaction via the cytochromic system P-450 and could be effective in patients with conco-
mitant pharmacotherapy. It does not affect the cognitive functions and that is why it is very suitable for the use by older and
anxiety patients. Although it has no sedative effect, it adjusts sleeping malfunctions.
Milnacipran seems to be a safe, well tolerated, and highly effective antidepressant in the treatment of intermediate to hard
depressive episodes with minimal undesirable effects.
It depends on our clinical experience whether milnacipran will become the medicament of the first line in depression tre-
atment [S. A. Montgomery, 1999].
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Boyer P., Briley M.: Milnacipran , a New Specific serotonin and noradrenaline reuptake inhibitor, Drugs of Today, 34/8/,709-720,1998.
Briley M.: From Dirty Drugs to Hyperselectivity and Part Way Back Again, Human Psychophartnacology,Vi1.12,S121-S125,1997.
Briley M.: Milnacipran, a Well Tolerated Specific Serotonin and Norepinephrine Reuptake Inhibiting Antidepressant, CNS
Drug Review,Vol.4, No2, pp137-148,1998.
Hindmarch I.: Do we need New Antidepressants?, Human Psychopharmacology,Vo1.12, S115-S119,1997.

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 Christodoulou G.N., Kontaxakisov Beata J.Havali, Kontaxakis Vassilis P.: Prevecnia depresie, WPA buletin o depresie,
Ro.5-.24, 2002, 3-9.
Kasper S.: Optimizing antidepressant treatment :are two actions better than one?, International Clinical Psychopharmacology,Vol.17,
June 2002.
Kasper S., Pletan Y., Solles A., Tournoux: Comparative studies with milnacipran and tricyclic antidepressants in the treatment
of patients with major depression: a summary of clinical trial results, International Clinical Psychopharnracology,1996,vol.11/
suppl. 4/ 35 39.
Kessler RC ,McGonagle KA, Zhao S., Nelson CB, Hughes M, Eshleman S, Wittchen Hu, Kendler KS: Lifetime and 12 months
prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.ArchGen
Psychiatry 51,8-19,1994.
Lecrubier Y: Milnacipran: The Clinical Properties of a Selective serotonin and Noradrenaline Reuptake Inhibitor SNRI/, Human
Psychophamracology, Vol.12,S127 S134,1997.
Lpine JP, Gastpar M., Mendlewicz J., Tylee A: Depression in the community: the first pan-European study DEPRES/Depression
Research in European Society/Int.Clinical Psychopharmacol.,12,19-29,1997.
Montgomery SA: From the theory to practice-everyday use of milnacipran, International Journal of Psychiatry in Clinical
Practice, Vol.,3,Suppl.2, PS29-S33,1999.
Montgomery SA: Dual action antidepressants in clinical practice, Drugs, 3,1,P43 P49,2001.
Moret C., Charveron M., Finberg J.P.M., Couzinier J.P., Briley M.: Biochemical Profile of Midalcipran/F2207/,1-Phenyl-1-
Diethyl-aminocarbonyl-2-aminomethyl- cyclopropane/Z/Hydrochloride, a potential fourth generation antidepressant drug,
Neurophamracology, Vol.24,Nol2pp 1211-1219, 1985.Nutt D.J.: The neuropharrnacology of serotonin and noradrenaline in depre-
ssion, International Clinical Psychopharmacology,17,Suppl.,S1-S12,2002.
Poirier M.F,Galinowski a.,Longevialle R.,Loo H.: Comparative study of rnilnacipran versus placebo on cognitive function in
healthy volunteers,. 3 erne Confrence Vigilance et Performances Psychomotorices Annecy,8-9-avril,1991.
Rouillon F.,Warner B.,Pezous N.,Bisserbe J.C., and the Milnacipran recurrence prevention study group, International Clinical
Psychopharnracology,15,133-140, 2000.
Spencer C.M., Wilde M.I.: Milnacipran: A review of its Use in Depression, Adis Drug Evaluation, Drugs, 56/3/, 405-427,1998.
Stahl S.M.:Are two antidepressant Mechanisms Better Than One?, Clinical Psychiatry, 58,8,1997.
Smolik P.:Duevn a behaviorlni poruchy, prvodce klasifikac, nstin nozognzie, diagnostika, Maxdorf-Jesenius,487: 1996.
Suchopr J.: Remedia,Compendium, Tretie vydanie,Panax ,743 1999.
vestka J.: SSRI lieky prvej volby, Maxdorf,Jesenius, 153,9,46-55,74-92, 1998.

HAMD, HAMA Scores

1st day of study After one month of milnacipran therapy After six months of milnacipran study
HA- HA-
HA-MA HA-MA HAMD HAMA
MD MD
1. 24 22 22 20 12 10
2. 25 23 18 18 11 6
3. 23 18 18 18 10 15
4. 18 8 16 8 6 6
5. 18 8 10 6 6 6
6. 18 10 16 10 8 6
7. 18 7 12 7 6 5
8. 25 10 18 10 0 0
9. 18 10 6 6 5 12
10. 28 38 22 21 12 11
Ave-rage 21.5 15.4 19.8 12.4 7.8 7.1

Table 1 PATIENT LIST

Number Avg.age
Men 4 44,25
Woman 6 40.66
Total 10 41,33

30
 Table 2 HAMD, HAMA Scores

1st day of study After one month of milnacipran therapy After six monts of milnacipran therapy
HA- HA-MA1 HA- HA-
MD2 HA-MA2 HA- MA3
MD1 MD3
Avg.points 21,5 15,4 19,8 12,4 7,8 7,1

TABLE 3 List of undesirable effect of medicament

Vertigo 0
Dry mouth 2
Anxiety 0
Obstipation 1
Dysuria 3
GIT malfunctions 1
Tremor 0
Palpitation 0
Nausea 0
Somnolence 0

CASUISTICS
Recent findings of Alzheimers Dementia possibilities and treatment in a psychiatric outpatients department
Ignjatoviov D., Ignjatovi M.
Psychiatric Outpatient s Department, Policlinics in Bansk Bystrica

FROM HISTORY TO THE LATEST FINDINGS

Dementia comes from a Latin word de-mens, without mind, is deterioration of intellectual capabilities and other cognitive
skills leading to decrease the capability to perform the common daily activities.
The findings of senile plaques in 1892 was first described by Blocq and Marinesco, but the beginning of the era of Alzheimer
s dementia is considered a clinical and pathological finding of pre-senile dementia in a 52-years old woman, who died four ye-
ars after demonstrating clinical symptoms of mental disorder and paranoid symptoms.
The principal histological feature was finding of plaques without neuro-fibral changes in cortex, hipocampal formation was
not involved in diagnostics at that time. This case was later studied using modern histological and molecular-genetic analysis,
involving screening for amyloid and precursor protein APP and apolipoprotein E /APO E/.
In 1910 Bonfiglio, Percusini and Kraepelin proposed differentiation of the Alzheimers disease form the common senile
dementia.
In 1976 Katzman proposed unification of the term pre-senile Alzheimer disease and senile dementia of Alzheimer type to
one nozologic unit. From 1980 the era of molecular pathogenesis of Alzheimer s dementia starts, from 1997 symptomatic tre-
atment of dementia and the year 2000 brings new modifications in treatment of Alzheimer s dementia.
The new researches /Winblad, Bogdanovic, OBrien, Lovestone/ prove, that Alzheimers disease is and it will be an illness of
the future and they try to clarify the pathogenesis of this serious progressing disease and also the new trends in treatment of
this third most frequent disease in the world.
A professor of psychiatry in Munich and neuropathologist Hans Frostl marked the three main strategies in treatment of pa-
tients with dementia:
Management of somatic situation
Influencing the cognitive functions
Influencing the behavioural disorders.
Different diagnostic criteria were created and accepted for Alzheimer s dementia, e.g.
Khatchaturians , CERAD /Consortium to Establish a Registry for Alzheimer s disease/, criteria, Tiens criteria, Braak and
Braak classification.
Khatchaturian and Tierny present plaques and girdles in cortical and/or hipocamal part, while CERAD prefers semi-quanti-
tative estimation of the maximum cortical affection with critical plaques.
The significant difference between Khatchaturian and CERAD criteria was, that the estimation of the number of plaques
can be done only from neuritic plaques, which results in the fact that neuritic pathology in clinical-pathological studies is more
significant in relation to occurring of dementia.

31
 The third group pd diagnostic criteria was presented by NINCDS - ADRDA /the National Institute of Neurological and
Communicative Disorders and Stroke - Alzheimer Disease Related Disorders Association/ a working group for clinical diagnosis
of Alzheimers Dementia and it was published by Tierny and col. in 1988.
They establish clinical criteria without neuropathological criteria for Alzheimers dementia based on finding pathologic
changes in hipocampus and/or neocortex. They also established excluding criteria for vascular disorders. Criteria for involving
and excluding Alzheimers dementia are variable, hipocampal and neo-cortical changes involving clinical-pathological approval.
Sjogren and col. Divided in 1952 disorders and decrease of the function of memory into several grades of importance for
clinical practice: the first grade = the loss of episodic memory accompanied by progressive deterioration, problems in finding
words, oscillation of moods, changes of personality, problems in performing daily activities, like e.g. check book balancing, de-
posits, withdrawals etc.
In the medium grade the progress of the disease is obvious - recognition of the family environment, learning new informati-
on, repaint of individual events / semantic memory/ starts to be progressively affected. Memorising of distant events is not qu-
ite lost. However, if the patients lose sense of time and space, they show agitation, and fail to interact with their environment.
In the last or terminal grade the new memory and old memory are quire disturbed, the patient is unable to perform the
common daily activities, he is unable to walk by himself, to chew, to eat, he becomes quite dependent of his nurses. The final
stage of Alzheimers dementia is coma and death, commonly as a result of infection /Gustaffson and col./

CASUISTICS
Patient E.M., born 30th of January 1923
Valid anamnestic data received from the daughter and the son in law of the patient -she overcame common infant diseases,
childhood was harmonic. Probably no hereditary disease occurred in the family, mother overcame lung tuberculosis, sister died
of a carcinoma of abdominal cavity. Family without dementia symptoms.
The patient completed eight grades of a grammar school, she worked as an independent employee in the State forests, later at
the commercial department, in the Slovak Bookshop, in Stavoprojekt and as an accountant of the Slovak Film Renting Company.
She got married as 22 years old, her husband died 74 years old, they had four children, one died of meningitis, other chil-
dren live. She had no operations, four child-births were normal, without complications, she did not use contraception. She does
not mention head injuries, she was never unconcious, she had no concussion, no fractures, she fell twice on an icy pavement,
without a fracture.
From her 73 years of age treated for the ischernic heart disease, compensated, she uses matipranolum and rutosidum.
Her character is rather calm, serious, slow.
From 1998 her daughter observed slowly developing memory and attention disorders. The patient started to forget, where
she put the things of daily use like a pen or glasses. At first she was not aware of it herself. Later she had worse orientation in
space, she got lost when she went to see her visitors off, she could not get back.
For disorders in orientation, memory and for the tremor of upper extremities the patient was sent by the general practitio-
ner to a neurological outpatient s department, where they expressed suspicion of morbus Parkinson. She was given biperide-
num, which was nottolerated well by her, for getting worse she was hospitalised at neurological department in January 1999,
where her dose of biperiden was changed and selegilin hydrochloride was added to the therapy. The patient was released in a
stabilised situation with the conclusion extra pyramidal hyper tonic hypo tonic syndrome.
On 5th of May a CT examination of the brain was performed with the conclusion of a finding corresponding to the age in
the inter-cranial structures without pathosmorphologic changes.
At the beginning of May 2000 the status of the patient worsened concerning memory disorders, orientation disorders, in-
tellectual deterioration, paranoid persecution hallucinations occurred in her mind and pseudo hallucinations in perception.
The patient was examined at a psychiatric out patient s department, we do not have the conclusion and she was recommen-
ded for hospitalisation.
The patient was hospitalised at the psychiatric department from 13th of May to 7th of June 2000 with the diagnostic conclusion
paranoid syndrome with dementia. She was given taiprid, biperidenum, metipranolum, rutosidum, thioridazini hydrochloridum.
She was first time examined at our psychiatric outpatient s department on 27th of June 2000 with the diagnosis probably
Alzheimer s dementia with later onset, differentially diagnostically atypical or combined type of Alzheimer s dementia, demen-
tia at Parkinson s disease and Lewy body dementia. We tested the patient by the series of tests where MMSE was 21 points.
Differentially diagnostically we excluded depression, where creeping onset, lasting over 6 months, variable mood, worse-
ned performance in the evening, bagatelisation of the disorder, answers on the kind a little bit outside the point, worsened
expression, meaning and worsened fluency of speech confirmed dementia.
Shortened questionnaire of geriatric depression according to Yesevage was 3 points /0- 5 points within limit/, i.e. did not
confirm depression.
The assessment scale ADL /Activity of Daily Living/ = 6 points, still complete self sufficiency. Assessment scale IADL /
Instrumental Activities of Daily Living/ = 7 points, /8 points = complete self sufficiency/.
The scale of self sufficienecy of a patient with Alzheimers disease - Psychical Self - Maintenance Scale /PSMS/ = 13 points,
score 6 means, that the patient can perform all the common daily activities, score 30 means that the patient is quite dependent
of the assistance of his environment and requires daily care.
Ischemic score of Hachinski and co. was 4 points, with score 0-4 points proves dementia of Alzheimer s type.
Clock test according to Schuman and co. We assessed by 3 points /mistakes in marking the time required/.

32
 We kept therapy with tiaprid, thioridazini hydrochloridum, metipranolum and rutosidum, we stopped biperidenum and we
started donepezil HCl in the initial dose 5 mg in the morning.
After three weeks of treatment we checked MMSE = 26 points /17/7/2000/. The patient subjectively reported improvement of
her memory /as if her memory came back, as the side effects she reported vomiting in the first two days. Hetero-amnesteticaly
according to her daughter s report she consider ably improved.
In the therapy we kept donepezil HCl 5 mg in the morning. The rest of the therapy idem. We ordered the patient for a check
up in four months.
During telephone consultations the patient s daughter complained of bad daily regime, that she eats little, she drinks only
4 dcl of water during the whole day, she has somaticproblems, she vomits and she has diarrhoea. We recommended to obser-
ve drinking regime and nutrition of the patient.
The check up on 13th of October 2000 - MMSE = 26 points. Abbreviated questionnaire of geriatric depression according to
J.A. Yesevage was 10 points, / 10- 15 points for manifest depression. The assessment scale ADL = 3 points, /self maintenance of
the patient worsened/. PSMS =22 points. Clock test = 5 points /severe disorders de organisation/
The patient subjectively reported worsened mood, worse self maintenance, increased tremor of the upper extremities and
feeling like vomiting. We gave her donepenzil for night in the same dose, we stopped thiorazin and we added maprotilinum
hydrochloridum. We recommended to hydrate the patient, to check the drinking regime and nutrition. In three days the dau-
ghter of the patient consulted the situation of the patient on the phone, she reported worsening, the patient is weak, she cannot
walk, she falls, she cannot eat or drink.
We recommended the patient for hospitalisation at the psychiatric department, where she was not admitted. She was sent
to internal department, where she was admitted for the suspicion of metabolic failure and dehydration.
The patient was hydrated but for economic reasons psychiatric medication was stopped, amentiforrn status appeared, which
was stressed by behavioural disorders and her daughter assessed the situation as the worst for the last three years of life
After re-hydration of the patient and internal treatment she improved, the amentiform status was not dominating in the
clinical picture. During hospitalisation in the internal department the psychiatrist was not consulted.
During the hospitalisation of the patient we were in a constant telephone contact with the patients family and after finishing hos-
pitalisation and re-convalescence in a family we called the patient on 14th March 2001 /10th month from the beginning of treatment
by dopenzil HCl for checking psychiatric examination, where according to subjective reports the patient now feels much better, she
communicates better with her environment, she can go for walks accompanied by a family member. According tot he data of her
grand son her character is the same as it was before, she is calm, serious, and according to her son in law she is more independent,
she solves crosswords by herself and she goes for walks, and she also cooks by herself.
We assessed MMSE = 29 points, Clock test = 3 points /mistakes in marking time required/, we assessed an abbreviated questi-
onnaire of geriatric depression according to
J.A.Yesevage, which was 5 points /0 -- 5 points within limits/, ADL = 6 points /complete self maintenance, IADL = b points, with 8
points = complete self maintenance, PSMS = 10 points /6 points mean that the patient cal perform all the common daily activities
without help, at 30 points he is quite dependent of the help and requires daily care/.
Actually the patient s therapy involves donepenzil HCl in the dose 5 mg pro die, maprotilinum 37,5 mg pro die and risperidon
0,5 mg pro die.

DISCUSSION
As with the improving care for old people the age limit moves upwards, there are more dement patients. Also there are more
patients with Alzheimer s dementia, which is the third most frequent disease after cardiovascular diseases and cancer according
to WHO 1999.
That is why an out patient psychiatrist faces responsible and very time demanding diagnostics of the patients with dementia and
their following treatment.
Maybe the best aid in diagnostics is taking anamnesis, MMSE, Clock test, Hachinski Iscemic Score and geriatric depression test.As
the most significant and the most simple indicator of the course of Alzheimers dementia MMSE and Clock test proved, which is the
most used one also in outpatients departments /80 - 90% validity/.
Finding in CT, MNR, is a very good aid in differential diagnostics, but not always the finding is significant and it is not decisive in
determining diagnosis. In out patient there was a CT finding without patho-morphological changes.
As the casuistic case we selected a patient with the probable Alzeimer s dementia of later type, in whom we diferentially diagno-
stically considered also atypical or combined type of Alzheimer s dementia, eventually dementia in Parkinson s disease. Symptoms
of tremor of upper extremities, probably bad toleration ofneuroleptic therapy, therapy by biperidon and virtual pseudo hallucinati-
ons as well as the negative CT finding lead us to considering Lewy body dementia.
After starting donepezil HCI , compared to the starting MMSE = 21 points there was improvement of 5 points after three weeks
from the beginning of treatment and after four months of treatment MMSE was the same. That means that cognitive skills did not
worsen any more, but we marked worsening in performing common daily activities, when after four months observation there was
considerable worsening of the patient s self maintenance, which proved progress of the disease, or for worsening somatic status
of the patient as a result of dehydration , also subjective experience of the patient worsened, which we observed also in the questi-
onnaire of geriatric depression according to Yesevage, which increased from 3 to 10 points.
The patient subjectively did not complain of memory disorders, but of the weakness, feeling like vomiting, no appetite, arm tre-
mor worsened.

33
 Nutrition of old people, keeping drinking regime, above all in patients with Alzheimer dementia are hard to observe, mainly if
the patient has no permanent nurse and family is not instructed on all that. This lead us to consideration of dehydration of the pa-
tient with the following states of confusion and behavioural disorders. That is why we recommended the patient for hospitalisati-
on at the psychiatry where she was not admitted. For the suspicion of metabolic failure she was admitted to internal department.
After applying adequate treatment, intersinic rehydration and after using psychiatric medication the situation of the patient im-
proved and stabilized.
In 10th month of observing the patient MMSE = 29 points, which is improving of 8 points, compared to the first examination, Clock
test = 3 points, improvement of 2 points compared tot he examination in the 4th month and the same status as in the first examination.
The questionnaire of the geriatric depression was in the 10th month of observation of the patient 5 points /within limits/, ADL =
6 points, improvement of 3 points compared to the 4th month and the same as in the first examination.
IADL = 6 points /with 8 points meaning complete self maintenance/ and PSMS= 10 points in 10th month of observing compared
to 13 points in the first examination and 22 ppoints in the 4th month of observing, which would prove improved self maintenance of
the patient and skills to perform all the common daily activities without help.
As Alzheimer s dementia is a life - long and fatal disease and besides the patient himself it also concerns the patient s family
members and nurses of the patient from 19th of March 2001 the family members of the patient actively participate of therapeutic
groups of Alzheimer s foundation in Bansk Bystrica.
That means that not only good diagnosis, quality treatment with the latest medication But also co-operation between specialists
and family can ensure good care for the patient in the old age.

CONCLUSION
Alzheimer s disease is a serious degenerative progressing brain disease which unites work of psychiatrists, neurologists, geron-
tologists, internists, pathologists, immunologists, genetics and also nurses and the patient s family themselves.
Alzheimer s disease means disease of the new millennium and a great challenge for all the specialists in finding new medicati-
on which enable to improve the life quality of patients with Alzheimer s dementia.

34
RIVASTIGMINE EFFICACY ON BEHAVIORAL AND PSYCHOLOGICAL
SYMPTOMS OF ALZHEIMERS DISEASE- FINDINGS FROM A 12-MONTHS
OUT- PATIENTS STUDY.

Authors
MUDr Milan Ignjatovi, Psychiatric Medical Office, Health Care Centre, Bansk Bystrica, Slovakia
MUDr Dana Ignjatoviov, Psychiatric Medical Office, Health Care Centre, Bansk Bystrica, Slovakia
MUDr Zeljko Tutujevi, Huddinge universitets jukhus, Behoendecentrum, Stockholm, Sweden

Summary
The number of patients suffering from Alzheimer s Dementia is increasing with the age of their life and is becoming one
of the important economic, medical, and social problems. The diagnostics of this disease is not complicated, but it requires a
good cooperation both of the patient and his family or those taking care of him.
In psychiatry different ways of Alzheimers Diseases therapy are used. Nowadays we use not only nootropic substances,
vasodilators, but also depenesil and rivastigmine. Galantamin registered in the Czech republic is being prepared for the mar-
ket. In our study we monitored the clinical symptoms of BPSD and with the help of MMSE we evaluated the cognitive functions.
Sixteen patients were observed / women N=12/ taking rivastigmine in average daily dosage from 9 mg to 12 mg pro die, in the
period from January 1, 2001 to January 31, 2002, that is during 12 months.
The average age of the patients was 79.88 years / from 71.0 up to 93.0 years of age/.
Fourteen patients met diagnostic criteria according to MKCH-10 and DSM- IV for Alzheimers Disease s dementia, atypical
or mixed type and two patients met diagnostic criteria according to MKCH-10 for Alzheimers Disease s Dementia with a late
start. MMSE in the zero- day / the initial examination/ was on average 15.75 points, in the sixth month = 21.75 points, and in the
twelfth month = 21.75 points. The average improvement was 6 points during the 12 months monitoring.
The improvement of behavioral and psychological symptoms of dementia was evident in the 2-nd and the 6-th month of
monitoring with the average daily dosage of rivastigmine from 9 to 12 mg pro die / table 3/.
Key Words
Alzheimers Disease /AD/, rivastigmine, Behavioral and Psychological Symptoms of Dementia, Mini Mental State Examination
/MMSE/
Introduction
Alzheimers Disease is a chronic and progressive neurodegenerative disease which is characterized by the reduction of ac-
tivity of daily living, behavioral disorders and diminution of cognitive functions /Mateffly I.,2001/.
More than two million people in the European Union suffer from Alzheimers Disease /Rocca WA, 1991/ .Amyloid plaques and
neurofibrillary balls are supposed to be responsible for an attack of Alzheimers Disease. Beta- amyloid is derived both from
beta- amyloid precursor protein and mutation on gene which is situated on chromosome 21.
These changes could be in connection with an early beginning of this disease in families with the genetic predisposition.
Alpha, beta, gamma- secretasies are involved in the process of beta- amyloid creation from the beta- amyloid protein pre-
cursor. It is also supposed that the early attack of Alzheimers Disease in families is caused by mutations on presenilin, the gene
bound to chromosome 14. Presenilin is an integral membrane protein, whose exact function is not knowisi yet. It is also suppo-
sed that a small amount of beta- amyloid experimentally can start a proinflammation response in vascular tissue and Dr Mullan
alleges that vascular diseases could be connected with Alzheimers disease.
As presenilin 2 is concerned, the gene on chromosome 1, it is well- known that it is connected with familial occurrence of an
early form of Alzheimers Disease. Presenilin 2 is highly homologous with presenilin I. Also APO E4 and specific allele of APO E
gene is often conected with sporadic form of Alzheimes Disease and the late beginning of familial form of Alzheimers Disease /
Mullan M.,2000/.Cholinergic theory, which takes part in explanation of the occurrence and development of Alzheimers Disease
is based on cholinergic deficit. There is the progressive loss of cholinergic neurons, especially in cortex and hippocampus, which
leads to diminution of available acetylcholine and later to reduction of activity of daily living, behavior disorders and diminuti-
on of cognitive functions of the patient. Physostigmine was introduced among the first substances of cholinergic type but it is
not in use now because of its short half-life period.
Subsequently tacrin was introduced but is not used due to its hepatotoxicity and discontinuous syndrome with dosage se-
veral times per day as well as interaction potential.
/Schneider LS, 1998, Changiz G., 2000, Corey- Bloom J., 1998/. It is also the substance with dual effect which means that it
has a central effect on AchE / acetylcholinesterase/ and BuChE / butyrylcholinesterase/ similarly to rivastigmine. It means that
the loss ofacetylcholinesterase is important in Alzheimers Disease and at the same time butyrylcholinesterase is enhanced in
cortex and hippocampus in 40 or even 60 percent of the whole cholinesterase activity.
This activity is partly the consequence of enhanced secretion of glias cells which are the main source of BuChE in the brain.
The rise of BuChE activity appears in those parts of brain which are mostly affected by Alzheimers Disease and is correla-
ted with the increase of markers of the disease progression/ one of them is also beta- amyloid delosition/.

35
 Dr Enz explains that it could be the evidence of the important role of BuChE in the course of the disease. Findings of the
author are that BuChE influences the transformation of benign beta- amyloid to neurotoxic plaques and inhibition BuChE can
reduce diseases progression /Mullan M., 2000/.
The group of patients and methodology
The group consisted of 16 patients, women N= 12, the average age 79.88 years / from 71.0 to 93.0 / with average MMSE =
15.75 points on the day of the initial examination, MMSE in the 6-th month was 21.75 points and in the 12-th month MMSE was
21.75 points.
Classifying criteria
MMSE in the range from 10 to 25 points
The age over 50
MKCH-10 and DSM- IV diagnostic criteria for Alzheimers Disease dementia with late occurrence and for Alzheimers Disease
dementia of atypical or mixed type.
the average changeable dose of rivastigmine from 9 to 12 mg pro die
the presence of BPSD and evident clinical symptoms of BSPD
monitoring during 12 months
To make the work simpler we did not use any structured scale - PDS/ Progressive Deterioration Scale/, CIBIC, ADAS-Cog.,
what can be considered as a shortcoming of the Work.
The other shortcoming was the small number of patients.
The aims of the study
To find out the changes in the cognitive functions of patients with Alzheimers Disease by long- lasting monitoring.
We evaluated MMSE on the zero-day/ the day of the initial examination/, the l-st month, 2-nd month, 6-th month and the
12-th month.
To monitor the symptoms, development and eventual diminution of BPSD of patients with Alzheimers Disease. For eva-
luation we used the scale for monitoring BPSD altered on the 7-th international congress of the International psychogeriatric
association /IPA/ in 1996/Benesova V.,2000.

Results
The results are shown in tables 1,2,3,4 and 5.
For the study we chose 16 patients with diagnosis F.00 and F.00.2 / Alzheimers Disease dementia/ who were taking rivasti-
gmine 9-12 mg per day. They were chosen according to classifying criteria and they were monitored from 1 January 2001 up to
31 January 2002.
With the help of MMSE we evaluated their cognitive deficit which was recorded on the zero day/ the day of the initial exa-
mination/, the 1-st month, 2-nd month, 6-th month and the 12-th month from the administration of rivastigmine. At the same
time we monitored occurrence, development and amelioration of behavioral and psychological symptoms of dementia in the
connection with administration of rivastigmine and antipsychotic and other psychopharmacologic therapy.
The age of the patients was from 71.0 to 93.0 years, the average age was 79.88 years. All monitored patients were polymor-
bid patients with polypharmacotherapy. In most cases cardiotonics and other drugs for cardiovascular diseases treatment
were administrated as well as diuretics and nonsteroidal antiflogistics. No patient taking rivastigmine noted any adverse reac-
tion. These by effects occurred most often: diarrhea, nausea and dyspepsia but there was no reason to discontinue the riva-
stigmine treatment.
Rivastigmine proved to be a safe drug not only for reduction of the cognitive deficit but also for diminution of behavioral
and psychological symptoms of dementia what considerably improved the quality of life of the patients with low doses of ta-
ken antipsychotic drugs.
Discussion
The studies which were monitoring the influence of rivastigmine on cognitive functions of the patients suffering from mo-
derately severe to severe form of Alzheimers Disease showed that after half- a year or one year of monitoring rivastigmine was
significantly more effective than placebo / Changiz G., 2000/.
It positively influenced not only the cognitive deficit but also the activities of daily living which in milder forms of Alzheimers
Disease are money operations, time determination, in moderately severe form of Alzheimers Disease the ability to dress one-
self, in severe forms the ability to have a bath, to eat, to give a telephone ring.
Certainly the behavioral symptoms were also improved/ Changiz G.,2000, Corey- Bloom J., 1998, Farlow M., 2000/.
We found out that in our monitored group MMSE was improved in 6.0 points from average 15.75 points on the zero- day/
the day of initial examination/ to 21.75 points in the 6-th month and after one year of monitoring MMSE was the same as in the
6-th month. Siinilar findings were mentioned in the foreign literature, too/Schneider LS,1998/.
In our study the improvement of BPSD was noticed mainly between the 2-nd and the 6-th month with the average daily do-
sage from 9 to 12 mg of rivastigmine per day. Similar results are noted in the studies from abroad, but they were evaluated with
PDS scale which included activities of daily living - ADL/Corey- Bloom J.,1998/. It was proved that patients who were taking daily
dose from 6 to 12 mg were significantly in better clinical state in comparison with patients who were taking from 1 to 4 mg of ri-
vastigmine per day or placebo. The evaluation was done in the 26-th week and it also referred to MMSE which was significantly
improved in comparison with patients who had 1-4 mg of rivastigmine or placebo. It is important to mention that preceding

36
Alzheimers Diseases attack there can be a slight cognitive deficit which is reflected in the rate of MMSE and patients compla-
ints of dysmnesia. Subsequently this disorder can be changed to Alzheimers Disease/Changiz G.,2000/.
There can be auxiliary methods in diagnosing of disorders of mind: functional MRI, then MRI aimed at hippocampu.s where
the athropy can be found. The athropy of hippocampus was found in Lewy body dementia, vascular dementia and Parkinson
dementia.
Dr Scheltens supposes that all these diseases contain the elements of Alzheimers Disease/Changiz G.,2000/.It was found
out that with the presence of BPSD administration of antipsychotic drugs can cause an impairment of Lewy body dementia
and in most cases drugs for cardiovascular diseases and neurological diseases dominate in the therapy/Grossberg G.T.,2000/.
In our work we most often used antipsychotics e.g. risperidon /average daily dose 0.85 mg/, tiaprid / 100 mg per day/, halo-
peridol /1.15 mg per day/ and from antidepressive drugs citalopram/ 20 mg per day/, sertralinum /25 mg per day/ and concomi-
tant therapy aimed at the polymorbid patients.
The patients were taking mostly drugs for the diseases of cardiovascular system, diuretic stimulants, antiflogistic agents
and others.
We did not note any pharmacodynamic interactions and adverse reactions while taking rivastigmine in combination with
other drugs/KVS, neurological/ what is mentioned also in foreign studies/ Grossberg G.T.,2000, Mullan M.,2000/.
There were some by- effects with the dose 6 mg per day like nausea, diarrhea, dyspepsia but they did not lead to the dis-
continuance of the therapy. This has also correlation with foreign studies/Corey- Bloom J.,1998/.
Older patients are a big load for those who take care of them and inadequately treated patients are a risk for their surroundings.
Real gerontopsychiatric pathology is situated mainly in nursing homes where the responsibility is put on the staff.
Thanks to new cholinergic substances - rivastigmine, we help those who take care of patients with Alzheimers Disease and
are directly involved in BPSD treatment. Rivastigmine improves the behavioral symptoms of patients with Alzheimers Disease
up to the stage which is similar to taking antipsychotics. It can be recommended as a drug which can be used in the future in
therapy of patients with behavioral disorders /Cummings J.,2000/.
Conclusion
According to the fact that the number of patients suffering from Alzheimers disease is increasing annually an early diagno-
stics and establishment of appropriate treatment enables the solution of this problem in a dignified way.
When BPSD appear different psychopharmaceuticals are used e.g. antipsychotics, antidepressants, bensodiazepins and
hypnotic agents .The antipsychotics can certainly cause impairment in some types of Lewy body dementia. We welcome every
possibility of treatment of these disorders with cholinergics.Previous studies as well as our work proved that they have good
influence on BPSD and thus they reduce prime and total costs on treatment of these patients what is a bennefit to those who
take care of them.
In our case the patients can get much benefit from dual effect of rivastigmine, its low interaction potential and good influ-
ence on BPSD and activities of daily life /ADL/ as well as on limitation of cognitive deficit.

Table No. 1 - Monitoring the cognitive deficit according to scales of appraisal of MMSE

MMSE day 1-st month 2-nd month 6-th month 12-th month
1 12 19 23 23 25
2 10 17 20 21 15
3 14 22 22 24 24
4 16 16 17 20 20
5 10 16 16 18 18
6 10 12 18 20 20
7 16 20 22 24 24
8 24 24 27 30 29
9 17 19 20 22 24
10 14 20 19 14 14
11 22 24 20 24 25
12 11 16 16 20 20
13 16 17 19 22 22
14 22 19 22 22 24
15 20 20 24 24 23
16 18 18 20 20 21
Average value 15.75 18.58 20.31 21.75 21.75

37
 Table No.2 - Psychological symptoms of dementia
day 1-st month 2-nd month 6-th month 12-th month

present absent present absent present absent present absent present absent

Delu-sion 7 9 7 9 7 9 0 16 0 16

Hallucinations 7 9 7 9 6 10 0 16 0 16

Paranoia 8 8 8 8 6 10 0 16 0 16

Depresion 4 12 4 12 3 13 1 15 1 15

An-xiety 7 9 7 9 6 10 1 15 1 15

Miside-ntification 1 15 1 15 1 15 0 16 0 16

Table No.3- Behavioral symptoms of dementia

0- day 1-st month 2-nd month 6-th month 12-th month

present absent present absent present absent present absent present absent

Aggresi- 5 11 5 11 4 12 0 16 0 16
veness

Confu-ssion 6 10 6 10 5 11 0 16 0 16

Dysso-mnia 10 6 10 6 8 8 0 16 0 16

Inadequate
behavior 2 14 2 14 0 16 0 16 0 16
when eating

Inadequat
sexual 2 14 2 14 0 16 0 16 0 16
behaviour

38
 Table No.4 - medicines used in the treatment of BPSD

Symptom Pharmaceuticals Average daily dosage

Psychotic symptoms Risperidon 0.85 mg
Tiaprid 100 mg
Haloperidolum 1.15 mg
Olanzapinum 1.15 mg
Agitation/aggressiveness Risperidon 1.16 mg
Haloperidolum 10 gtt.
Anxiety Clonazepamum 0.5 mg
Alprazolamum 0.5 mg
Depression Maprotilinium 10 mg
Sertralinum 25 mg
Citalopramurn 20 mg
Dyssomnia Zolpidem 10 mg
Nitrazepamurn 5 mg

Table No. 5 - Survey of cardiovascular pharmacotherapy and neurological therapy and other pharmacotherapy
used in patients with Alzheimers Disease:

Pharmaceuticals used in therapy of the diseases of Isosorbidi mononitras/monosan/Sorbimon

cardiovascular system Glyccroli trinitras/Nitromack
Nifedipinum/Corvaton,Corinfar
Verapamili hydrochloridum/isoptin
Diltiazemi hydrochloridum/Blocalcin
Isradipinum/Lomir
Pentoxiffilinum/Agapurin/Trental
Diuretics Furosemidum/Furon/Furosemid
Cardiotonics Digoxinum/Digoxin
NSA/nonsteroidal antiflogistics Diclofenacum natricum/Dixlofenac
Inflamac, Vral, Voltaren
Insulins Insulini suspension/Insulin
Others Vitamins E,B,C

Bibliography
Beneov V., Behaviorlne a psychologick priznaky demencie, es. a Slov. Psychiat., 96,20000.No.1.pp.30-37
Costa Jermone F.,Ravi Anand, Neal R. Cutler, Richard Hartmann, Linda Manclone, John J.Sramek, Amy Veroff: Correlation
Between Cognitive Effects and Level of Acetylcholinesterase Inhibition in a Trial of Rivastigmine in Alzheimers Patients ,Poster
Presentation No.561, Convention center,Lower Level, Hall D, Wednesday, May 19,3.00-5.00 PM.
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68/Abs.S 79.002.
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in Patients with Mild to Moderately Severe Alzheimers Disease,Eur. Neurology 2000,44,236-241.
Grossberg G.T.,Hannes B. Stahelin,John C. Messina, Ravi Anand and Jeoffrey Veach: Lack of Adverse Pharmacodynamic Drug
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stna prezentcia,Novartis.

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 Mtffy l.,: Dulna inhibcia rivastigminom, nov trendy v liebe Alzheimerovej choroby,Bratislava,3.12.2001, stna pre-
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40
CHRONIFICATED AGORAPHOBIA WITH PANIC DISORDER
MONITORING DURING ONE YEAR INTERVAL AND ASSUMPTION OF
COMORBIDITY WITH DEPRESSION UPRISE

AUTHORS
MUDr. Milan Ignjatovi, Psychiatric Medical Office, Health Care Center, Bansk Bystrica
MUDr. Dana Ignjatoviov, Psychiatric Department, F. D. Roosevelts Hospital, Bansk Bystrica

SUMMARY
We chose 16 patients, 11 women and 5 men from the group of patients who were monitored in the psychiatric medical offi-
ce with diagnosis of agoraphobia with panic disorder that lasted for more than 2 years. Thirteen of them continued in the tre-
atment for 1 year and 3 patients didnt finish the therapy. From the patients who didnt finish the therapy, 2 patients were exclu-
ded after 1 month and they werent diagnosed with comorbidity of depression and patient didnt visit medical office after 1 year
even though she was diagnosed with comorbidity of depression (HAMD- 17= 25 points).
We diagnosed comorbidity of depression in the study base-line in 3 men and 6 women who represent the majority of pati-
ents who finished the study. The rate of comorbidity was 2 men and 5 women after 1 month therapy, 1 man and 2 women after
3 months therapy and there was no occurence of comorbidity of depression after 1 year.
Depression was evaluted according the HAMD-17 scale, when HAMD= 7 and more (3).
Eminent occurence of depression comorbidity in patients who suffer from agoraphobia with panic disorder after one year
therapy suggests that new drug therapy of SSRI, specifically of paroxetinum with additional management of clonazepanum and
good compliance is successful in this case.

KEY WORDS
Chronificated agoraphobia with panic disorder, comorbidity of depression, SSRI, paroxetinum, clonazepamun

INTRODUCTION
Disorder that lasts for more than 2 years and is exacerbated for more than 2 months in one year interval is defined as chro-
nic. In regard to continuous misunderstandings or unwillingness to make a compromise between Anglo-Saxon and American
authors who are involved in this problem, agoraphobia with panic disorder is differently listed in DSM-IV and ICD-10 classifica-
tions. The question is, if the panic attack uprose as the first one (DSM- IV) and agoraphobia is developing afterward or agorap-
hobia is the first diagnosis and panic attack uprise afterward (ICD-10). Of course, if authors would make a compromise, great
amount of our disorders became chronic, as well as according to the first sentence in our study, where the definition of chronic
disorder was noted (its related e.g. to the chronic obstructive lung disease and as well as other somatic disorders).
Following criteria are listed in evaluation of development, uprise, crest, retreat and recovery of agoraphobia with panic dis-
order: attacks rate, anticipatory anxiety intensity, comorbidity and patients personality.
We focused on possible depression comorbidity in the process of agoraphobia with panic disorder chronification.
Amer V. Starevi et al (4), panic attack precedes the depression uprise in majority of all cases. But agoraphobia with panic
disorder uprose after depression uprise in high percentage of patients (40%) (4).
When there is comorbidity of agoraphobia with panic disorder and depression, the percentage interval is 24- 91% and the
disorder uprise path is very important- depression mostly uprises after agoraphobia with panic disorder development (5).
Afterward author notices that comorbidity can be in % described as interval from 25 to 68% of cases with generalized anxious
disorder, with specific phobias from 20 to 50% of all cases, with social phobia from 9-64% of all cases as well as with alcoholi-
sm from 5 to 41% of all cases.
It is important to notice that these kind of panic disorder are listed in DSM- IV: 1. small (abortive) panic attacks, 2. panic
attacks with no clinical signification (non-clinical attacks), 3. panic attacks during a sleep (night panic attacks), 4. panic attack
without anxiety sensing( 6).
Differential diagnosis of agoraphobia with panic disorder is quite difficult, especially when we take into consideration the
above stated facts, dynamics of disorder and comorbidity as well.
Disease process is connected to appropriate diagnosis and treatment in the majority of all cases.
We can be restricted by pharmacological and economical conditions and by the influence of health insurance companies
on the reduction of drug prescription (2). But important fact is that pharrnacoeconornics is just introducing itself into clinical
practice and it will be important in the future.
Thats why drugs should not be chosen according to pharmaceutical companies advice nor restrictions but according to
availability and effectiveness in concrete cases (2).

GOAL
To reach the knowledge about paroxetinum effectiveness in chronificated agoraphobia with panic disorder conditions in
the case of comorbidity of depression, eventually compliance.

41
HYPOTHESIS
Paroxetinum should be effective drug in a case of agoraphobia with panic disorder as well as in a case of depression comorbidity.

METHOD
Outpatients who suffer from agoraphobia with panic disorder for more than 2 years and who developed comorbidity of de-
pression were involved in the study.

INVOLVING CRITERIA:
men and women older than 18 yearspatients who suffer from agoraphobia with panic disorder according to DSM- IV and ICD-10
possibility of depression comorbidity uprise, HAMD- 17= 7 and more
patients informed written agreement to be involved in the study

EXCLUDING CRITERIA:
men and women older than 70 years
history of schizophrenia
organic disorder
mental retardation
personality disorder
pregnancy
alcohol addiction and other addictions
The study was permitted by Ethic Committee of NsP Brezno on the 3rd of August 1999.
Patients were involved in the study during one year interval from the day, when the study was ratified by Ethic Committee,
i.e. from 03.08.1999 till 03.08.2000.
Tests such as HAMA, API (acute panic inventory test) HAMD- 17 (3) were realized before management of paroxetintun and
clonazepamum in some cases as well. Wash-out was interval of 3 days in case of previous psychopharmacotherapy (in case of
unsuccessful treatment in others psychiatric medical offices).
All the tests were repeated after 1 month, 3 months and after 1 year. All obtained data underwent statistical analysis and
were prepared for presentation.

MODALITY OF TREATMENT
After 3 days wash-out period patients received 20 mg of paroxetinurn at the beginning, dosing was various up to maximal
dose of 40 mg per day. Whereas the goal of study was monitoring of agoraphobia with panic disorder improvement and in ca-
ses with depression comorbidity monitoring of depression improvement as well, we didnt count the average dose.

EVALUATION
HAMA, HAMD- 17, API- 0., 1st, 3rd month and one year evaluation

CASUISTIC
49 years female patient, married, in partial disability annuity, half time employed as governess, with diagnosis F.40.01, suffers
from symptoms for 7 years. She was treated in psychiatric department and frequently checked in psychiatric medical office
during noted time, almost everything was tried in the treatment, starting with benzodiazepins, SSR1 and finally RIMA (moclo-
bemid) which she stopped to receive by herself because she was despairing from the experiments. Her condition was confir-
med by HAND- 17= 21 points, HAMA= 25 point; API= 30 points. Patient was sent by neurologist who monitored her for suspect
psychomotoric epilepsy which never really uprose, besides non- significant EEG result because of which she received carbama-
zepinum (Biston 200 mg in the dose of 1 tablet in the morning- no tablet in the noon- 1 tablet in the evening.) Neither this tre-
atment satisfied her. We suggested the diagnosis from patients first sentence when she said that she has vertigo, palpitation,
cant breath, sweats and has needles and pins in her hands and suffers from headache as well, when she travels by bus to visit
primary doctor. She recovers during one day, lying in bed with severe non- responding tension headaches after noted control
visits. We consulted the patients case with neurologist, reduced carbamazepinum up to half dose, managed paroxetinurn (20
mg per tablet) in dose of 1 tablet in the morning and clonazepamum (0,5 mg per tablet) in dose of 2 mg per day. HAMD-17 sco-
re fell down to 20 points, HAMA to 22 points, API to 28 points and after 3 months HAMD- 17 was 19 points, HAMA= 18, API= 26.
After one year HAMD-17 was 9, HAMA= 11, API= 14 points.
After long term persisting anticipating anxiety patient after the initiating of treatment visited her daughter in Austria, trave-
ling by bus by herself. She repeated the visit this year as well. She was not even able to travel because of her disorder in previous
time. From the group of symptoms that patient had in our first meeting, she still has mild, rare tension headaches responding
to common analgesics which uprise especially when she is exhausted.

42
RESULTS
There were 16 patients involved in the study, 11 women and 5 men, table 1. The youngest patient was 28 years old, the oldest
one was 56 years old, average age was 39,68 years, table 2.
Obtained education is listed in table 3, 3 women finished elementary school, 5 women and 5 men finished specialized secon-
dary school, no patient finished secondary grammar school and 3 women graduated the university.
The list of diagnosis that were made in our psychiatric medical office is in table 4. The average time of symptoms duration
was 8,06 years, the longest duration was 16 years and the shortest one was 2 years- table 5. Thirteen patients continued the
treatment, 3 patients didnt finish the treatment, table 6.
From the group of 13 patients who finished the treatment the comorbidity of depression was diagnosed in 3 men and 6 wo-
men, comorbidity of depression was diagnosed in 2 men and 5 women after 1 month, in 1 man and 2 women after 3 months and
no patient has depression after one year, table 7.
Average HAMD- 17 score was 18,84 at the beginning of the study, afterward HAMD-17 was 15,07 after 1 month, HAMD- 17=
10,76 after 3 months and HAMD- 17= 7,92 after 1 year. There was improvement in the HAMD- 17 scores up to 3,77 points, i.e.
up to 20,01% in first testing according to the treatment of agoraphobia with panic disorder and depression comorbidity. The
HAMD- 17 scores improvement was up to 4,31 points, i.e. 22,87% in the second testing and up to 2,84 points, i.e. up to 14,86%
in the third testing. The final improvement (comparing the first and the last HAMD- 17 scores) was up to 10,92 points, i.e. up
to 57,96%, table 8.
The average HAMA scores were 25,92 points at the beginning of treatment, HAMA= 21,76 after one month treatment, HAMA=
20,53 after 3 months and HAMA= 14,07 points after one year treatment. The improvement of HAMA was up to 4,16 points, i.e.
up to 16,04% in the first testing, up to 1,23 points, i.e. up to 4,74% in the second testing and up to 6,46 points, i.e. up to 24,92%
in the third testing. The final improvement comparing the first and the last HAM.A scores was up to 11,85 points, i.e. up to 45,71
points, table 9.
There are average scores of API tested at the beginning of the treatment, one month and one year later in the table 10. The
improvement of API was up to 2,00 points, i.e. up to 8,93% inthe first testing, up to 3,77 points, i.e. up to 16,84% in the second
testing and up to 4,46
points, i.e. up to 19,92% in the third testing. The final improvement of API (comparing the first and the last API scores) was
up to 10,23 points, i.e. up to 45,71% in average.

DISCUSSION
According to Eri (1), necessary factors for panic attack prognosis are: 1. Biological bases of panic condition, especially in-
tensity and uprise rate of panic attacks, 2. Patients age, when disorder uprose, 3. Disorder duration, 4. Disorder process, 5.
Existence of specific
intrapsychic and interpersonal conflicts, 6. Patients motivation for treatment, 7.
Hypersensitiveness and reactivity of patient to managed drugs (1).
The advantages of SSRI in compare with other classical drugs, e.g. imiprarninum which used to be managed in a case of ago-
raphobia with panic disorder in previous time, are hidden in point 6.
Panic attack is a disorder which follows agoraphobia very often. According to Starevi, it happens in 91% of all cases and it
can be complicated by others disorders within comorbidity afterward.
According to ICD-10, agoraphobia with panic attack is classified as residual diagnostic category that can be used only in case
it fulfils own criteria. In case depression would uprise we should use the diagnosis of affective disorder and agoraphobia with
panic disorder should be classified as comorbidity. It is different in DSM- IV classification, where panic disorder with or without
agoraphobia can be assigned to the group I of other disorders like depression, alcoholism, isolated phobias.
Panic disorder in DSM- IV classification was not assigned as self- existent unit. This fact reflects different modalities betwe-
en DSM- IV and ICD- 10.
This fact should not make our workshop more difficult because both classifications are available. Appropriate diagnosis and
treatment can be a problem.
Daily practice experiences show that paroxetinurn is effective in a case of agoraphobia with panic disorder, as well as that
terminal phase of this disorder in the process of chronification is an affective disorder- depression.
The primary disorder in our patients was agoraphobia with panic disorder but high HAMD-17 scores which were 18,84 in
average at the beginning, were in normal level of 7,92 points after one year, table 8. That was the same in case of anxiety, when
HAMA was 25,92 points in average at the beginning and 14,08 points which is a normal level after one year, table 9. API was re-
duced from 22,38 points at the day zero to 12,15 points after one year, table 10.
Thereby the hypothesis that paroxetinum is effective in the treatment of agoraphobia with panic disorder as well as in cases
of depression comorbidity was confirmed. Of course the therapy algorithms of one or another disorder must be used and the
dose of paroxetinum must be sufficient (whereas, patients often receive insufficient dose of paroxetinum because of physicians
fear of overdosing stimulation at the beginning of therapy, what can be amplified by the usage of benzodiazepin, e.g. clonaze-
parnurn in low dose of 1- 2 mg per day). Sufficient and qualitative patients compliance is necessary as well.
Supporting psychotherapy is welcome in each of these cases.

43
CONCLUSION
Sixteen patients were chosen from the group of patient who were monitored in psychiatric medical office because of dia-
gnosis of agoraphobia with panic disorder that lasted for more than 2 years, 11 women and 5 men. Thirteen of them continued
the treatment during one year, 3 patients didnt finish the treatment- 2 patients who have not been diagnosed with comorbi-
dity of depression were excluded after one month. One female patient who was diagnosed with depression comorbidity didnt
come for control checking after one year (HAMD-17= 25 points).
We confirmed comorbidity of depression in the majority of patients who stayed in the study at the base- line of study, what
is represented by 3 men and 6 women.
There was comorbidity of depression in 2 men and 5 women after 1 month, in 1 man and 2 women after 3 months and there
was no patient with depression comorbidity after 1 year.
Depression was evaluated by HAMD- 17 scale, where HAMD-17 was 7 points and more.
Higher occurence of depression comorbidity in patients who suffer from agoraphobia with panic disorder for more than 2
years suggests that new drug therapy of SSRI, of paroxetinum with additional clonazepamum therapy and good compliance is
successful in this case.
BIBLIOGRAPHY
Eri Lj., Panina stanja II, dopunjeno i proireno izdanje, Beograd- Zagreb, 1991, 1-331, 215
Hosk L., Farmakoekonomika v psychiatrii, Galn 2000, 7- 133, 111, 112, 107, 108
Paunovi V., Tirnotievi I., (1992): Instrumenti klinike procene u psihiatriji, Izdava IDP nauna knjiga Beograd, 1- 151, 116, 117
Starevi V., Uhlenhuth EH, Kellner R., Pathak. D. 1993a: Comorbidity in panic disorder: II Chronology of appearance and pat-
hogenic comorbidity. Psychiatry Reasearch, 46: 285- 293
Starevi V., Uhlenhuth EH., Kellner R., Pathak D. 1992a: Patterns of comorbidity in panic disorder and agoraphobia. Psychiatry
Research, 42: 171- 183
Starevi V. Beograd, 1997: Stanja stracha u klinikoj praksi, 1- 234, 37, 129- 130, 132- 134

TABLE 1 - SURVEY OF PATIENTS

Number of patients Absolute number Percentage

Women 11 68,75
Men 5 31,25
16 100

TABLE 2 - AGE OF PATIENTS

The youngest patient 28 years old

The oldest patient 56 years old
The average age of patient 39,68 years

TABLE 3

Number % Number %
Elementary School 3 18,75 - -
Specialized Secondary School 5 31,25 5 31,25
Secondary Grammar School - - - -
University 3 18,75 - -
Total 11 68,75 5 31,25
women men

44
 TABLE 4 - SURVEY OF PATIENTS DIAGNOSIS IN PSYCHIATRIC MEDICAL OFFICE

Women Men
F.40.01 9 4
F.40.2 1 -
F.41 1 1

TABLE 5 - DURATION OF DIFFICULTIES

The average duration of difficulties 8,06 year

The longest duration of difficulties 16 years
The shortest duration of difficulties 2 years

TABLE 6 - END OF TREATMENT

Number Percentage
Continued in treatment 13 81,25
Did not continued in treatment 3 18,75

TABLE 7 - COMORBIDITY WITH DEPRESSION

Men Women Other patients without comorbidity with depression

At the beginning of 3 6 4
examination
After 1 month 2 5 6

After 3 months 1 2 10

After 1 year - - 13

TABLE 8 - HAMD- 17 TESTS EVALUATION

The average values HAMD-17 at the HAMD1 = 18,84 HAMD1-HAMD2 = 3,77 point, i.e. average improvement by 20,01%
beginning of examination
The average values HAMD-17 after 1 HAMD2 = 15,07 HAMD2-HAMD3 = 4,31 point, i.e. average improvement by 22,87%
month
The average values HAMD-17 after 3 HAMD3-HAMD4 = 2,84 point, i.e. average improvement by
HAMD3 = 10,76
months 14,86%
The average values HAMD-17 after 1 HAMD1-HAMD4 = 10,92 point, i.e. average improvement by
HAMD4 = 7,92
year 57,96%

TABLE 9 - HAMA TESTS EVALUATION

The average values HAMA at the HAMA1 = 25,92 HAMA1-HAMA2 = 4,16 point i.e. average improvement by 16,04%
beginning of examination
The average values HAMA after 1 HAMA2 = 21,76 HAMA2-HAMA3 = 1,23 point i.e. average improvement by 4,74%
month
The average values HAMA after 3 HAMA3-HAMA4 = 6,46 point, i.e. average improvement by
HAMA3 = 20,53
months 24,92%
HAMA1-HAMA4 = 11,85 point, i.e. average improvement by
The average values HAMA after 1 year HAMA4 = 14,07 45,71%

45
TABLE 10 - API (ACUTE PANIC INVENTORY) TESTS EVALUATION

The average values API at the beginning of API1-API2 = 2,00 point, i.e. average improvement by
API1 = 22,38
examination 8,93%
The average values API after 1 month API2 = 20,38 API2-API3 = 3,77 point, i.e. average improvement by
16,84%
The average values API after 3 month API3 = 16,61 API3-API4 = 4,46 point, i.e. average improvement by
19,92%
API1-API4 = 10,23 point, i.e. average improvement by
The average values API after 1 year API4 = 12,15 45,71%

46
PSYCHOPHARMACOTHERAPY OR PSYCHOTHERAPY OF ANXIETY
DISORDERS- ONE YEAR RESULTS

AUTHORS
Milan Igniatovi (1)
Dana Ignjatovi (2)

Psychiatric out Department of Policlinic, Bansk Bystrica, Slovak republic

Psychiatric out Department of Policlinic, Bansk Bystrica, Slovak republic

PURPOSE
The puropose of our one year study was a comparison of psychopharmacotherapy and psychoterapy of acute out-patients
with anxiety disorders during crises periods

PATIENTS AND METHODS

We had 20 patients/ 16 female/ they used psychopharmacotherapy and psychotherapy very individually for 12 weeks.
Patients used hydroxizin/50 mg pro die for two weeks,with flexible dose titration during 12 weeks and decreasing to minimum/.
10 patients finished their psychotherapy and 10 patients didnt finish the psychotherapy.
We made standard psychological tests- API/ acute panic inventory test/, HAM-A, HAM-D,BECK.

KEY INCLUSION CRITERIA:

male and female out - patients aged 18 years
DSM IV diagnosis and ICD - 10 classification for panic disorders, phobic disorders, reactive depression, adaptation disor-
ders, personality disorders, somatoform disorders
Patients had been treated in our out - patient department during one year without controlled group and without placebo
double - blind group

SUMMARY AND RESULTS

We compare our one year experiences with treatment of out-patients with anxiety disorders. After a short time therapy
the effect was significant- the improvement of the clinical symptoms and successful come back to every day life activities.
Patients, that have finished their treatment by alliance were without reziduum by treatment with benzodiazepins and tre-
atment without relevant psychotherapy.
Combination of psychopharmacotherapy and psychotherapy results in decreasing of clinical symptoms of anxiety disorders.
Diagnosis of our patients- table No 1
Using psychotherapy in the first week of treatment 100% of our patients had been participated, in the 4 th week it had been
60% of them and in the 8 th week it had been only 15 patients.Table No2
Using psychopharmacotherapy in the first week 100% of our patients used hydroxizin, in the 4 th week it had been 45% and
in the 8 th week all of our patients had been without psychophamracotherapy.Table No 3.
Decreasing of clinical symptoms had influence to psychopharmacotherapy and psychotherapy.

CONCLUSION
In acute anxiety disorders first step to be successful in the treatment is adequate initial psychopharmacotherapy/hydroxizin
was tolerated by patients during initial crises, without sedation and cognitive disturbance/.
In psychotherapy are the most important first 6 weeks of therapy and very important is an alliance:patient-psychiatrist.
At the end we would like to thanks to prof.Gillieron and prof. Schneider from Policlinique Psychiatrique Universitaire in
Lausanne and Dr. Eva Bryois-Hanic to understand dynamic short-time psychotherapy.

References
Eva Bryois-Hanic,MD:Intervention Psychoterapique en Quatre Seances, 1994
J.C.Samuelian:Effects on the cognitive functions of two anxiolytical treatments in patients,who suffer from general anxiety
A.De Brabander:Effects of hydroxizin on Attention and Memory, 1990
M.Slab:Preparat Atarax v perorlnej medikcii u det,1997
M.Ferreri:A multicentre double -blind placebo controled study investigating the anxiotytic efficacy of hydroxizin in patients
with generalized anxiety, l995

47
week
1 2 3 4 5 6 7 8 9 10 11 12
DG
F.32.1
x x x x x x K

F.32.2
x x x x x D

F.32.2
x x x D

F.40
x x x S

F.40
x x x - D

F.40
x x x x x x K

F.40.1
x x x S

F.41
x x - - - - x x S

F.41.1 x x x x x x K
F.41.1
x x x x x x K

F.41.1
x x x x D

F.41.1
x x x x x x K

F.41.2
x x x x x x x x x K

F.43.2
x x x x K

F.43.2
x x x x x x K

F.45.3
x x x x x x x x K

F.60
x x S

F.60
x x x S

F.60
x - - x H
F.60
x x H

%
100 95 80 60 45 40 15 15 5

48
 Psychotherapy during 12 weeks

Week
1 2 3 4 5 6 7 8 9 10 11 12

DG

F.32.1
x x x x x x K
F.32.2 x x x x x D
F.32.2 x x x D
F.40 x x x S
F.40
x x x sine th D

F.40 x x x x x sine th K
F.40.1 x x x S
F.41
x x - - - - sine th sine th S

F.41.1
x x sine th sine th sine th sine th K

F.41.1 x x x sine th sine th sine th K

F.41.1 x x x sine th D
F.41.1 x x x x sine th sine th K
F.41.2
x x x x x sine th sine th sine th sine th K

F.43.2 x x x sine th K
F.43.2 x x x x x x K
F.45.3 x x x x x x x sine th K
F.60
x x S

F.60 x x x S
F.60
x - - x H

F.60
x x H

%
100 95 75 45 30 15 5 0 0

Psychopharmacotherapy during 12 weeks

49
 The way how patients finished their therapy

Table 4

All
The number of weeks 1 2 3 4 5 6 7 8 9 10 11 12 patients %
Dg. F.32.2 1
Male
% 5 5
Agree-
ment Dg. F.32.2 F.40, 3
F.41.1
Female
% 5 10 15

Dg. F.43.2 1
Male
% 5 5

Contact F.32.1,
Dg. F.41.1 F.40, F.41.1 F.41.1 8
F.41.1 -3x
Female
% 5 25 5 5 40

Dg. F.40.1 1
Male

By % 5 F.41 5
patient
Dg. F.60 F.40 F.60 5 4
Female
% 5 5 5 20

Dg. F.60 1
Male
% 5 5
Hospita-
lisation
Dg. F.60 1
Female
% 5 5

All 2 3 4 2 6 2 1 20
patients

Total % 10 15 20 10 30 10 5 100

50
 Table 5

Psychopharmacotherapy we used during 12 weeks male

Week
1 2 3 4 5 6 7 8 9 10 11 12
DG
Alprazolam Alprazolam Alprazolam Alprazolam Alprazolam
(0,5) 1tbl.v. (0,5) (0,5) (0,5) (0,5)
Citalopram 0-1/2-1 0-1/2-1 0-1/2-1 0-1/2-1
(20) 1-0-1 Citalopram Citalopram Citalopram (20) Citalopram
F.32.2 (20) (20) 1-1/2-0 (20) D
1-1/2-0 1-1/2-0 Maprotilin (25) 1-1/2-0
Maprotilin (25) 1-1-1 Maprotilin (25)
1-1-1 1-1-1
Haloperidol Haloperidol
gtt. 5kv./noc gtt. 5kv./noc

Hydroxizine Hydroxizine Hydroxizine

F.40.1 1/2-1/2-1 1/2-0-1 1/2-0-1 S

Fluoxetin Fluoxetin Fluoxetin Fluoxetin Fluoxetin Fluoxetin

1-0-0 1-0-0 1-0-0 1-0-0 1-0-0 1-0-0

F.43.2

D - therapy finished by alliance

S - therapy finished by patient
K - therapy finished by contract

Table 6 a - Psychopharmacotherapy we used during 12 weeks-female

Week

1 2 3 4 5 6 7 8 9 10 11 12
DG

Citalopram Citalopram Citalopram Citalopram (20) Citalopram Citalopram

(20) (20) (20) 1-0-0 (20) (20)
F.32.1 1-0-0 1-0-0 1-0-0 Zolpidem 1/n 1-0-0 1-0-0 K
Zopiklon 1/n Zopiklon ex Zolpidem 1/n Zolpidem Zolpidem
Zolpidem 1/n 1/n 1/n

Sertralin Sertralin Sertralin

F.32.2 1-1-0 1-1-0 1-1-0 D

51
 Hydroxizine Hydroxizine Hydroxizine
1/2-1/2-1 1/2-1/2-1 1/2-1/2-1
F.40 Fluoxetin Fluoxetin Fluoxetin S
1-0-0 1-0-0 1-0-0

Hydroxizine Hydroxizine Hydroxizine

F.40.0 1/2-1/2-1 1/2-0-1 0-0-1/2 sine th D

Sertralin Sertralin Sertralin Fluoxetin Fluoxetin

F.40 1-1-0 1-1-0 Fluoxetin 1-0-0 1-0-0 sine th K
1-0-0

Fluoxetin Fluoxetin
1-0-0 1-0-0
F.41 Bromazepam Bromazepam - - - - sine th sine th S
(3) 1-0-0 (3) 1-0-0

Hydroxizine Hydroxizine
1/2-1/2-1 1/2-1/2-1

F.41.1 sine th sine th sine th sine th K

Hydroxizine Hydroxizine Hydroxizine Hydroxizine ex

1/2-1/2-1 1/2-1/2-1 1/2-1/2-1/2

F.41.1 sine th sine th K

D - therapy finished by alliance S - therapy finished by patient

K - therapy finished by contract H - hospitalisation

Table 1

The number The number The number of male

Diagnosis of patients % of female % %

F.32.1 1 5 1 5 - -
F.32.2 2 10 1 5 1 5
F.40.0 3 15 3 15 - -
F.40.1 1 5 - - 1 5
F.41.0
1 5 1 5 - -

F.41.1 4 20 4 20 - -
F.41.2 1 5 1 5 - -
F.43.2 2 10 1 5 1 5
F.45.3
1 5 1 5 - -

F.60* 4 20 3 15 1 5
Spolu
pacientov 20 100 16 80 4 20

*pacient with diagnosis F.98.5

52
DIFFERENTIAL DIAGNOSTICS OF PANIC DISORDER AND FOLLOWING
TREATMENT AT THE PSYCHIATRIC CLINIC - OUR 1 YEARS EXPERIENCE

AUTHORS
MUDr. Milan Ignjatovi, Psychiatric Clinic, NsP Brezno (Hospital with Polyclinic)
MUDr. Dana Ignjatoviov, Psychiatric Department, F.D. Roosevelts Hospital, Bansk Bystrica
PhDr:Vladimir urik, CSc.,Technic University Zvolen, Faculty of Ecology and Environmental, Slovak republic

SUMMARY
44 women and 8 men at the age of 20 to 62 years with chronification of panic disorder have often used to be tediously and
hardly diagnosed and on the basis of that also inadequately treated.
The diagnoses, which most often appear in case of these patients are: dorsalgia, vertigo, migraine, epilepsy, tachycardia and
other disorders.
These patients often use to be treated on somatic ailments for many years and in most cases they are recommended to a
psychiatrist by chance, many times only after exhausting all possibilities at other colleagues. The patients use to be treated by
different preparations, as for psychopharmacotherapy, they most often they get benzodiazepines.
A great part of the patients have lost hope that once they would be better. In many cases they have been diagnosed and tre-
ated by the psychiatrists themselves as neurastenia.
Of course, the therapy remained the same and during many years it has not changed.
As today we have a wide pallet of medicaments from SSRIs and we can use them as causal treatment in case of these pa-
tients, we suppose that on the basis of these possibilities a new stage in the treatment of chronificating panic disorder have
been opening.

KEY WORDS
differential diagnosis, panic disorder, agoraphobia, pseudo-epileptic seizure, migraine, vertigo, SSRI, benzodiazepines

INTRODUCTION
The neurosis of fear first time appeared in 1895 and it was named by S. Freud himself and its further development can be
monitored till nowadays, when it has been renamed to panic disorder with agoraphobia or without agoraphobia in the latest
classifications DSM IV and ICD 10. Marks and Klein belong to physicians who contributed to its introduction in DSM III/ 1980.
Also other authors in our country, as well as abroad are engaged in this disorder. As for neurologists, they are: P. Kukumberg,
R. Kotas in the Czech Republic, I. Rektor. They are neurologists, who try to find a connection and differences between migraine,
epilepsy, panic seizure and other psychic disorders.
In Yugoslavia, Eri Lj. is engaged in this problematic and tries to find his own multi-modal method of treatment, by which
we can help these patients.
In Switzerland, Baumann P. and Bryois Ch. are engaged in rational treatment with benzodiazepines. Diagnosing panic dis-
orders with agoraphobia is sometimes tedious and tiresome for the patient, as well as the physician. Much depends on the
patients personality, on his/her compliance. The treatment can be long /S. Kasper, 1999/ and in many cases also unsuccessful.
The patience can be the only assistant in treatment of such disorders.
The patients come with different difficulties, massive therapies, without substantial effect and several diagnoses of soma-
tic character. The most frequent of them are: dorsalgia, migraine, epilepsy, vertigo, tachycardia and others, which cannot be
treated in the standard way. The patients already are at the end of their tether after multiple examinations and the long-term
treatment. Dysphoric tuning?, neurastenic elements and even depression can appear as co- morbidity.
Treatment with clomipramine and denyodiazepines /J. Raboch, 1999/, cognitive-behavioural psychotherapy /J. Prako, 1999/
have been the most frequent treatment of such disorders till the discovery of SSRIs. These are methods, by connection of
which the most successful treatment has been reached. At present, the offer is extended by RIMA and SSRI. Their effect in the
practice persuaded not only experts-psychiatrists, but also practical physicians.

METHOD AND GROUP OF PATIENTS

52 patients have been chosen on the basis of 3 including criteria: all answer the diagnosis panic disorder according DSM IV
and ICD 10, the disorder has been not lasting less than 3 months and the up-to-now treatment and self-treatment has been not
successful.
Monitoring and evaluation of the results took place from February 1, 1999 to February 1, 2000 at the Psychiatric Clinic.

MONITORING
The results are based on the retrospective clinical monitoring of the patients medical records, where the focus has been on
diagnosing, differential diagnosis and the therapy. There are 2 casuistic cases for illustration, all patients remained filed at our
clinic, the smaller number of patients finished the treatment and the others continue with the treatment.

53
CASUISTIC No. 1:
Patient, 32 years old, married, without neuro-psychiatric problems in the family and in case history. She is a teacher, from
the beginning of ailments: working disability. Before one and half year she started to feel worse and the physicians during 4-5
months tried to find out the reason of her ailments. She subjectively described the ailments as: reeling in the head, heart bea-
ting, hindered breathing, nausea, fear of travelling by bus, later fear of going outside to the street without her husband and of-
ten repeating of the above mentioned ailments.
She has been examined by internists with a negative diagnosis and she underwent the HEAD-UP TILT test, which has been
described by her as an unbearable examination, during which she fell into senselessness. She has been diagnosed as vasodepre-
ssoric syncopic state, disposition for vagovagal collapses and vertiginous syndrome and tachykardia. Symptomatic treatment
metoprololi tartas has been started and she has been left home. The internist sent her to our Psychiatric Clinic , we diagno-
sed the panic disorder with agoraphobia, we started with paroxetinum with clomazepamum in small dosage / paroxetinum 20
mg pro die and clonazepamum 1 mg pro die / and the state of the patient has improved. The vertiginous ailments, tachycardia,
tachypnoe, as well as the fear of travelling passed away. At present, the patient gets only 10 mg of paroxetinum daily as a main-
taining dosage and she is fully addicted to her work duties and family.

CASUISTIC No. 2
The patient, 52 years old, she is a worker, disable to work for a long time because of vertigo, headaches, heart beating, pins
and needles in hands and legs, choke feeling, fear of travelling by bus, going outside the house, staying among strangers, fear
of going shopping alone, without being accompanied by her daughter or somebody else and frequent repeating of the above
mentioned troubles.
In the family case history of the patient the mother and the father were alcoholics and the patient, together with brothers
and sisters, was placed to an orphanage.
The patient first time felt bad before 14 years, when she has been in a spa, she started to pass out, to have head reeling, he-
art beating, hard breathing. That time nothing was found out, she was treated by neurologists on cervical migraine, vertebro-
genous algic polytop syndrome and one time she used 8 types of different drugs.
At the entry to out Psychiatric Clinic, the following has been used in her therapy: bisoprololi fumaras, oxetoroni hydroge-
nofumaras, betahistini dihydrochloridum, diclofenacum natricum, alprazolamum, metamizolum natricum. Either the long term
treatment did not improved her state at all. The patient was disable to work for a long time, the medical commission conside-
red her to be a malingerer. It has been problematic for her to explain her troubles and they menaced her that she would lose
the financial subsidy. After the first meeting with her we finished the treatment with the exception of bisoprololi fumaras and
we started with paroxetinum and clonazepamum /dosage: paroxetinum 30 mg pro die and conazepamum 2 mg pro die/ and we
recommended the patient to a group therapy. The treatment at our Psychiatric Clinic begun in April 1999 and during a month
the patients state improved, the headaches remained, but they have been milder, pins and needles in the hands mildened and
the patient started to travel by bus without difficulties and without an accompanying person. The patient did not have verti-
gos, heart beatings and feeling of choke. At the beginning of the group therapy experienced also several panic seizures among
strangers - co-patients, which have been treated with intramuscular injection of diazepam. In August the patient returned to
the work, she bears well psychic, as well as physic load. She is fully addicted to her family and the youngest juvenile daughter.
At present, the patients therapy constists of paroxetinum 20 mg pro die, clonazempamum 1 mg pro die, natrium ? mg pro
die and sulphirid 50 mg pro die.

RESULTS
The studied group o patients consisted of 52 patients: 44 women and 8 men, the patients have been at the age of 20 to
62 years. The average age of the men has been 35.87 years, the average age of the women has been 39.61 years. The shortest
ailments of a patient lasted 3 months, the longest 30 years, the average 6.29 years. The average duration of a treatment at our
Psychiatric Clinic has been in average 4.71 months, the shortest 1-days /of course unsuccessful/, the longest 11 months.
The state of the most patient is stabilized - at 19 patients, the mitigation and reduction of the numbers of panic seizures
and withdrawal of agoraphobia at 15 patients, 14 patients independently finished the treatment, most frequently after the first
examination. At 4 patients less frequent, but strong panic seizures lasted - they have been suffering from panic disorder with
agoraphobia for a long time.
In the treatment of these patients we most frequently used paroxetinum - at 38 patients as the basic treatment, clonazepa-
mum as the adjuvant treatment. 9 patients used citalopramum and the rest of patients, with the exepction of one female pati-
ent /dosulepinum/ had SSRI as the basic treatment.
Besides the biological data we would like to underline also the psychical pre-disposition for the origination of the panic dis-
order, which is often in the character of the patient, itself, Eri calls it anxious character and it is the mixture of characteristics
of an evasive and dependent personality. Eri recommends the study of the personality structure and the patient diagnosing of
the panic disorder with agoraphobia or without agoraphobia The anxious character is not included in any classification, but it
helps to understand the disorder in other way, like it is understood in other medicinal fields. He itself states also the multimo-
dal method of treatment and recommends as the treatment of 1st option the drugs from the SSRIs group and enzodiazepines
in combination with the relevant psychotherapy /Eri, Lj., 1991/. Also the Czech authors accept the medicamentous SSRI and
RIMA therapy, but they prefer the cognitive-behavioral therapy or the combination of the both.

54
 The treatment itself of the patients, who have been suffering of the panic disorder with agoraphobia for many years, is not
easy, but after diagnosing or eventually finishing the diagnosing of other disorders, who accompany the panic disorder, a te-
dious and patient treatment follows.
It is recommended to continue with the treatment minimally for one year, then to stop the treatment after an agreement
with the patient or to leave the maintaining therapy /Kasper, S, 1999/. Our experience is the necessity of the long-term monito-
ring of the patient and a careful reduction of the therapy and its finishing. The rational manipulation should above all concern
besides SSRIs also benzodiazepines /Baumann P., Bryois Ch., 1999/. Not only once it happened that the patients, who used bro-
mazepamum, alprazolamum, and in practice they even did not know, what disorder they are treated on, had abstinent appe-
arances in case of switching to other treatment. In such cases the compliance was not bad and some of these patients decided
to be treated at those physicians, who prescribed them benzodiazepine.

CONCLUSION
The panic disorder is not a hard disease, even if the clinical picture often seems very dramatically and the diagnostics of
the panic disorder is very difficult and delicate medicinal procedure, which requires an experienced and patient physician. /
Eri Lj., 1991/.
The differential diagnostics of the panic disorder requires to return to the beginning of the disorder itself, to the first disco-
very of completely first symptoms of panic disorder, as well as to monitor the dynamic course of the disorder during the years.
The personality structure at such disorders is very important and besides these psychical basis, the neurobiological serotnoni-
nergous theory is given by us to the connection with complicated revealing and diangostics of the panic disorder /Kukumberg
P., 1999, Kotas R., 1999, Rektor I., 1999/.
Thanks to psychopharmaca from SSRIs and the rational therapy with benzodiazepines, the therapy of a diagnosed chroni-
fied panic disorder, or its comorbidity with other disorders becomes treatable.
The multimodal treatment, including psychotherapy, has an extremely important task in this process.
BIBLIOGRAPHY
Baumann P., Bryois Ch. /8/ 1999/: Usage rationeell des benzodiazepines, Pharmacia and Upjohn, 4-30
Eri Lj. / 1991/: Panina stanja II. dopunjeno i proireno izdanje, Medicinska knjiga, Beograd-Zagreb, 153-175
Kasper S./4/1999/: Diagnostics and Pharmacoherapy of Panic Disorder, issue: Psychiarie No.4/1999, 242-247
Kotas R, Ambler Z. /1999/: Serotonine receptors in patophysiology and migraine treatment, Czech and Slovak Neurol.
Neurochir., 62/95, 1999 /1/8-12
Kukumberg P./1999/: Panic disorder and migraine, Czech and Slovak Neural. Neurochir., 62/95, 1999/1/57-59
Raboch J., Seifertov D., Prako J./1999/: Panic states, issue SKB, 18-24, 26-52
Raboch J., Seifertov D., Prako J./1999/: Panic states, Part II, issue SKB, 6-17
Rektor I., Tyrtlkov I., Brzdil M./1991: Psychically induced non-epileptic /pseudo-epileptic/ seizures, Czech and Slovak Neural.
Neurochir., 62/95, 1999/1/44-49
koda Ct./1996: Non-distinguished psychiatric disease in a non-psychiatric surgery, Practical physician 76, 1996, 2-5

TABLE 1. - SOMATIC PATIENTS EXAM INED WITH MRI

MRI NUMBER %
MALE 12 52.17
FEMALE 11 47.82
TOTAL 23
% 100

MEAN AGE OF PATIENTS

MALE 44.33
FEMALE 41.36
MEAN AGE OF ALL PATIENTS 42.91
THE YOUNGEST PATIENT 21
THE OLDEST PATIENT 63

The second group included 9 patients treated in the psychiatric outpatient clinics, and out of that number 4 were men
(44.44%) and 5 women (55.55). The mean age of men was 42 years, of women 35.2 years, the youngest patient was 25 and the
oldest was 51 (Table 2).

55
 TABLE 2. - REVIEW OF PSYCHIATRIC OUTPATIENTS EXAMINED WITH MRI

MRI NUMBER %
MALE 4 44.44
FEMALE 5 55.55
TOTAL 9
% 100

MEAN AGE OF PATIENTS

MALE 42
FEMALE 35,2
MEAN AGE OF ALL PATIENTS 38,22
THE YOUNGEST PATIENT 25
THE OLDEST PATIENT 51

Exclusion criteria helped us reduce the comorbidity to the minimum among patients with somatic diseases.
Patients with somatic diseases tested with MRI (6 patients) had diagnoses G.00-G.99 (diseases of the nervous system) and
M.00-M.99 (diseases of muscular, skeletal and collective tissues (also 6 patients) (Table 3).

TABLE 3. - DIAGNOSES OF PATIENTS WITH SOMATIC DISEASES EXAMINED WITH MRI

DIAGNOSIS DIAGNOSIS IN WRITING NUMBER OF PATIENTS %

C00-C99 TUMOURS 5 21.73
D10-D36 BENIGN TUMOURS 1 4.34
E00-E90 DISORDERS OF THE 2 8.69
GLANDS OF
INTERNAL SECRETION
G00-G99 DISORDERS OF THE 6 26.08
NERVOUS SYSTEM
I00-I99 DISORDERS OF 1 4.34
CIRCULATION
M00-M99 DISORDERS OF 6 26.08
MUSCULAR, BONE
AND CONNECTIVE
TISSUES
R00-R99 SUBJECTIVE AND 1 4.34
OBJECTIVE SIGNS,
ABNORMAL CLINICAL
AND LABORATORY FINDINGS, UNCLASSIFIED
ELSEWHERE
S00-T98 INJURIES, POISONING 1 4.34
AND OTHER
COMPLICATIONS
TOTAL 23
% 100

Within M.00-M.99 diagnoses, the ratio of dorsalgia was 50% (M.54) - Table 4; and in the G.00-G.99 group, there was no pre-
dominant diagnosis (Table 5).

DIAGNOSIS DIAGNOSIS IN WRITING NUMBER OF PATIENTS %

M49 SPONDILOPATIE 1 16.66
M51 OTHER DISORDERS OF INTERVERTEBRAL DISKS 2 33.33
M54 DORSALGIA 3 50
TOTAL 6
% 100

56
 TABLE 5. - REVIEW OF THE MOST FREQUENT DIAGNOSES AMONG SOMATIC PATIENTS EXAMINED WITH MRI

G00-G99 DISASES OF NERVOUS SYSTEM

DIAGNOSIS DIAGNOSIS IN NUMBER OF PATIENTS %
WRITING
G32 OTHER 1 16.66
DEGENERATIVE
DISORDERS OF NS
NOT OTHERWISE
CLASSIFIED
G40 EPILEPSY 1 16.66
G43 MIGRAINE 1 16.66
G45 TEMPRORARY BRAIN 1 16.66
AND ISHEMIC
SEIZURES AND RELATED SYNDROMES
G62 OTHER 1 16.66
POLENEURO-PATHIES

G81 HEMIPLEGIA 1 16.66

TOTAL 6
% 100

In regard to the number of MRI, the greatest number of patients, i.e., 13 (56.52%) were examined with MRI for the first time
(Table 6) which made the group more homogenous and comparable.

TABLE 6. - NUMBER OF MRI EXAMINATIONS IN PATIENTS WITH SOMATIC DISEASES

SEQUENCE OF MRI NUMBER OF PATIENTS %

FIRST 13 56.52
SECOND 7 30.43
THIRD 1 4.34
FOURTH 1 4.34
FIFTH 1 4.34
TOTAL 23
% 100
All patients suffering from agoraphobia with panic disorder (9) were examined for the first time on MRI (Ta-
bles 7 and 8).

TABLE 7. - REVIEW OF DIAGNOSES OF PSYCHIATRIC OUTPATIENTS EXAMMIED WITH MRI

DIAGNOSIS DIAGNOSIS IN WRITING NUMBER OF PATIENTS %

F.40.01 AGORAPHOBIA WITH PANIC DISORDER 9 100

TABLE 8. - NUMBER OF MRI IN PSYCHIATRIC OUTPATIENTS

SEQUENCE OF MRI NUMBER OF PATIENTS %

FIRST INVESTIGATION 9 100

The psychological evaluation before and after non-invasive examination (MRI) was carried out with the use of international
scales of API test. After MRI in patients with somatic diseases, their condition improved, on average, by 1 point, i.e. 9.96% (API
test), among patients who received paroxetin the improvement after MRI was 4.66 points, i.e. 46,7%. At start, the mean value
for both groups on API 1 test was 10 points.
This comparison indicated that patients, on average, endured MRI better after they had received premedication with paroxetin.
The feeling of tension decreases before the examination, and therefore, hypothesis 2 was confirmed, i.e. that premedicati-
on makes the patient more comfortable, reduces the tension and enables completion of MRI.

57
 In the group of somatic patients examined with MRI, API 1 or 2, seven patients had scored above 15 and, of this number the
improvement occurred only in 3 patients on API 2. One among these 7 patients had the same score on API 1 and API 2 (Table 10)

TABLE 10. - REVIEW OF DIAGNOSIS AND MEDICATIONS IN SOMATIC PATIENTS EXAMINED WITH MRI,
WITH API 1 OR API 2 SCORE ABOVE 15

MRI/diagnosis Sequence of MRI API 1 API 2 Score Therapy

C78 First 17 14 -3 Does not know which
medication he/she takes
G32 first 22 9 -13 No pharma-cotherapy

G43 first 20 29 +9 ketoprofen, B vitamins

M51 first 22 6 -14 analgetics, antirheumatics
M54 second 16 40 +24 no pharmacotherapy
M54 third 8 22 +14 biperiden, lorazepam, antirheumatics
R42 first 21 21 0 does not know
Total 126 143 +17
Mean value 18 20.42 +2.42

A randomly selected patient with somatic disease, who at the time of MRI examination had G.45 diagnosis scored 10 on API
1, 3 on API 2, and took daily dose of paroxetin 20 mg 1-1- 0 tablets 2 weeks before MRI (Table 9). Even when we consider this
randomly selected somatic patient, it was paroxetin up to its daily dose that helped him endure the investigation in a more re-
laxed manner, although the medication with paroxetin was not planned in the study.

TABLE 9a. - RESULTS OF PSYCHOLOGICAL TESTS

SOMATIC PATIENTS PSYCHIATRIC OUTPATIENTS (who had previously

been treated for a long time in order specialized
outpatient departments)
NMR/ diagnosis API 1 API 2 Score NMR/ dia- API 1 API 2 Score
gnosis
C04 0 1 +1 I51 11 2 -9
C71 3 3 0 I11 20 8 -12
C71 0 0 0 Q23 19 5 -14
C72 2 6 +4 G43 10 6 -4
C78 17 14 -3 I11 23 1 -22
D33 3 3 0 G99 2 0 -2
D33 6 11 +5 S01 2 2 0
E22 9 0 -9 G43 0 19 +19
G32 22 9 -13 G43 3 5 +2
G40 7 4 -3
G43 20 29 +9
G45 10 3 -7
G62 11 4 -7
G81 9 6 -3
I64 15 8 -7
M49 4 4 0
M51 5 9 +4
M51 22 6 -16
M54 16 40 +24
M54 14 0 -14

58
 M54 8 22 +14
R42 21 21 0
S32 7 3 -4
total 231 208 -23 total 90 48 -42
mean value 10.04 9.04 -1 mean value 10 5.33 -4.66
% 9.96 % -46.67

TABLE 9b. - RESULTS OF PSYCHOLOGICAL TESTS

SOMATIC PATIENTS PSYCHIATRIC OUTPATIENTS

NMR/ dia-gnosis API 1 API 2 Score NMR/ diagno-sis API 1 API 2 Score
C04 0 1 +1 F4001 11 2 -9
C71 3 3 0 F4001 20 8 -12
C71 0 0 0 F4001 19 5 -14
C72 2 6 +4 F4001 10 6 -4
C78 17 14 -3 F4001 23 1 -22
D33 3 3 0 F4001 2 0 -2
D33 6 11 +5 F4001 2 2 0
E22 9 0 -9 F4001 0 19 +19
G32 22 9 -13 F4001 3 5 +2
G40 7 4 -3
G43 20 29 +9
G45 10 3 -7
G62 11 4 -7
G81 9 6 -3
I64 15 8 -7
M49 4 4 0
M51 5 9 +4
M51 22 6 -16
M54 16 40 +24
M54 14 0 -14
M54 8 22 +14
R42 21 21 0
S32 7 3 -4
total 231 208 -23 total 90 48 -42
mean value 10.04 9.04 -1 mean value 10 5.33 -4.66

% 9.96 % -46.67

In addition, of particular interest were 3 cases with increased score on API 2 (Table 11). One of them was a female patient
with diagnosis G.43 and score +9, who had the following experiences during the examination: she did not feel the right part of
her body, she had a dry mouth, tremor, arrhythmia, difficulties with breathing, she did not feel well but endured the whole in-
vestigation (i.e., her condition detenorated).

59
 TABLE 11. - REVIEW OF SOMATIC PATIENTS INVESTIGATED WITH MRI WHOSE CONDITION DETERIORATED ON
API 2 TEST
MRI/ DIAGNO-SIS API 1 API 2 SCORE EXPERIENCE OF MRI

G43 20 29 +9 arrhythmia, difficulties with

breathing, carried the MRI
procedure to the end
M54 16 40 +24 feeling of isolation, MRI procedure
discontinued
M54 8 22 +14 arrhythmia, MRI procedure
discontinued
TOTAL 44 91 +47
MEAN VALUE 14,66 30,33 +15,65

Another patient with diagnosis M.54 who scored +24 (deterioration during MRI) experienced a very unpleasant feeling of
anxiety, he felt as if he was placed in the coffin, he could not move. He experienced the noise as the work of the compressor for
breaking the asphalt on the street, and he requested the examination to be discontinued after 30 minutes. He had difficulties
with breathing, a feeling that he would suffocate and that he would faint, he felt sick and could not complete MRI to the end.
The third patient scored +14 (also deteriorated during the investigation). He had arrhythmia, difficulties with breathing, did
not feel well, he was dizzy, and for these reasons he asked, on his own initiative, the investigation to be discontinued after 20
minutes.
These patients enabled us to better understand our hypothesis 1, which they confirmed, i.e., about a precipitating MRI effect
on the development of panic attack among patients whose diagnosis was still not precisely established.
Nevertheless, although there were only few such cases among somatic patients (only the condition of 3 patients deteriora-
ted and was accompanied by panic anxiety) we must take into consideration that this was the number of deteriorations from
the total number of investigated somatic patients (23), and the study covered only those who were examined with MRI during
one clinical week.
There are also some other questions which were left unanswered such as, for example, why some patients were tested with
MRI for the second, or third time, and whether the therapy they received during the process of making differential diagnosis
was effective or not and whether it was related to their main disease.
Of 9 psychiatric outpatients patients who received premedication with paroxetin, 3 scored above 15 on API 1. The mean sco-
re was 20.66 and their condition improved, on average, in API 2 by 4.66 points, the mean value of improvement was 16 points.
This indicates that the patients waited for the investigation with specific psychological tension and uncertainty that disappea-
red during the investigation (Table 12 ).
Deterioration of one patient who scored 0 on API 1, was 19 on API 2. She had acute panic attack during the investigation,
which was resolved with 2 mg of clonazepam (Table 12).

TABLE 12. - RESULTS OF PSYCHOLOGICAL TESTS OF PSYCHIATRIC OUTPATIENTS, WHO ARE TREATED WITH
PAROXETIN AND EXAMINED WITH MRI, AND WHOSE CONDITION IMPROVED AFTER MRI (ON API 2)

MRI/ DIAGNOSIS API 1 API 2 SCORE

F.40.01 20 8 -12
F.40.01 19 5 -14
F.40.01 23 1 -22
TOTAL 62 14 -48
MEAN VALUE 20,66 4,66 -16

All this illustrates the possible increase of the score on API 2, in which case, it enables the follow-up of precipitation of panic
attack in somatic patients, as well as in patients premedicated with paroxetin, which is presented in Tables 11 and 13.

TABLE 13. - RESULTS OF PSYCHOLOGICAL TESTS OF THE PSYCHIATRIC OUTPATIENTS, WHO ARE TREATED WITH
PAROXETIN AND INVESTEGATED ON MRI, AND WHOSE CONDITION DETERIORATED AFTER MRI (ON API 2)

MRI/ DIAGNOSIS API 1 API 2 SCORE

F.40.01 0 19 +19
TOTAL 0 19 +19

60
Discussion
As we have already mentioned at the beginning of the paper, we could not find similar studies in the literature, and we can
only confirm that there are various precipitating factors of panic attack2,3,4
We have found that the patients who did not receive premedication with paroxetin had worse experiences. concerning MRI
procedure (Tables 9a, b, 10 and 11), and that they showed increased score on API 2 test.
The very experience of MRI procedure was different, they were anxious, weak, they felt as if they were placed in the coffin,
could not breathe, as if they would suffocate, they had stomach problems, nausea, urge to vomit, they were unable to comple-
te MRI investigation, they had fear of death, a feeling that they had the cage on their head, a shortage of air as if the air in the
room did not change. The very work of the MRI machine they experienced as unpleasant noise, as if compressor machine for
breaking the asphalt on the street was right by their ear.
The vast majority of diagnoses that the patients brought with themselves (Tables 9a and 9b) were M.54, G.43 which had
been most commonly consulted with psychiatrists, but unfortunately for the patients, only after investigations that had lasted
for too long at other departments. These diagnoses were dorsalgia, migrainous diseases, and other. The patients who received
paroxetin which has a strong anxiolytic and sedative effect and reduces the frequency of panic attacks at certain time intervals,
endured the investigation, on average, 4 times more easily compared with patients who received no premedication with S.S.R.I
group of medications (paroxetin).

Conclusion
This was pilot study with a small sample and we are planning to continue the investigation since the findings indicated that
paroxetin may be very useful, if not with all patients investigated on MRI, then in patients with psychiatric diagnosis.
Furthermore, paroxetin can be useful for somatic patients, for example, patients with insufficiently differentiated diagnosis
of dorsalgia and migrainous problems. This could facilitate the work of our colleagues who work with RTG (MRI) and help our
patients to endure more easily and without panic attacks these, sometimes, necessary noninvasive (MR1) procedures.
References:
Timotijevi 1, Paunovi V. 1nstrumenti klinike procene u psihijatriji, IDP Nauna knjiga Beograd, 1992, 1-151, 116-117.
Eri Lj. Panina stanja. II dopunjeno i proireno izdanje, Medicinska knjiga, Beograd - Zagreb, 1991, 1-309, 7-12,133-152.
Raboch J, Seifertov D. Prako J. Panicke stavy, vyd: Psychiatrick spolenost esk Ikarsk spolenosti J.E.Purkyn, 1999,
I. ast,1-54, 18-24, 11 ast,1-56, 6-40.
Robert E. Hales, Stuart C.Yudovsky, John A.Talbott. Textbook of Psychiatry, 2nd Edition, the American Press, 1994, 1-1608,
495-554.
Milan IGNJATOVIC, psychiatrist, Psychiatric Outpatient Clinic, Policlinic, Banska Bistrica, Slovakia

61
IS COMBINATION OF PSYCHOPHARMACOTHERAPY AND
PSYCHOTHERAPY EFFECTIVE AT TREATMENT OF AGORAPHOBIA
WIHT A PANIC DISORDER?

AUTHORS
MUDr. Milan Ignjatovi 1.
MUDr. Dana Ignjatoviov 2.

1. Psychiatric out-patients department, Policlinic, Horna 60, Banska Bystrica, The Slovak Republic
2. Non-state psychiatric out-patients clinic, Cesta k nemocnici I, Banska Bystrica, The Slovak republic

Summary
Brief dynamic individual psychotherapy is often used at the psychiatric out-patients clinics in treatment of anxiety disorders.
Broad-spectrum antidepressants of the SSRI (serotonin selective reuptake inhibitors) group contribute profoundly to a
combined treatment with psychotherapy.
A very important question is whether pharmacotherapy or psychotherapy alone are sufficient in treatment of anxiety disor-
ders. Our 39-month long observation at psychiatric out-patients clinics shows that patients who were subjected to a brief dyna-
mic individual psychotherapy in combination with pharmacotherapy had better results after the treatment was finished. They
have been without pharmacotherapy for 10.5 months on average after taking pharmacotherapy continuously for 12.25 months.
In comparison, the other group members have been subjected only to the ordinary psychiatric interview and have been taking
the drugs on average for 25.94 months and they are still taking them.

Key words
Brief dynamic individual psychotherapy, psychopharmacothcrapy, agoraphobia with a panic disorder

Introduction
Anxiety is a part of a range of natural human emotions. And not only that. Anxiety is the oldest universal emotion of a human
kind and a primary emotion of every man. Anxiety has different variations from a slight one to a panic attack /Kalicanin, 1996/.
Also with view to such statements it can be concluded that it is desirable to combine pharmacotherapy and psychotherapy
within a multimodal way of treatment anxiety disorders with adults. /Eric, 1991/. Some authors recommend combining both the-
rapies also with children /Tadic, 1992/.
As to the biological foundations of the psychotherapys effect, according to the Kandels experiments on animals, psychothe-
rapy is considered to be a form of learning, where the process of learning that occurs in psychotherapy can induce alterations
of gene expression and thus also a change of synaptic transmission /Gabbard, 2000/.
There are also authors who take into account only biological foundations of agoraphobia with panic disorder, for example
due to hypofunctioning of presynaptic noradrenergic receptors and adaptation hypersensitisation of postsynaptic noradre-
nergic receptors.
Naturally, this hypothesis includes also serotoninergic, GABA-ergic, cholecystokinergic systems /Landowski, 1999/.
For us, the out-patients clinic psychiatrists, the clinic experiences, in addition to the theoretical considerations and experi-
ments on animals, are of utmost importance.
In Sweden, 62 patients who suffered from agoraphobia with panic disorder were followed up for 16 years and it was dis-
covered that only 10 patients had not had any anxiety symptoms for the last 10 years and had not had to take psychopharma-
cotherapy /Andersch, 2002/.
A small number of cured patients in this study, frequent changes of psychopharmacotherapy, not utilising psychopharma-
cotherapy during the 15 years of observations represent the same problems that we encounter in our daily out-patients clinic
practice. Questions that we often ask ourselves are: What is the most effective therapy for patients with agoraphobia with pa-
nic disorder, how long it should last and how long a patient should be in remission following the therapy.

Group and Methodology

8 patients suffering from agoraphobia with panic disorder who took psychopharmacotherapy and at the same time un-
derwent depth-oriented individual psychotherapy were found in the patients register of the first author of the study /Group
A/. On the other hand there were 15 patients with the same diagnosis who took psychopharmacotherapy and underwent only
ordinary psychiatric interview /Group B/.
Average age of the patients in Group A was 36.5 and in Grout, B 41.06 years.
Follow up and assessments of the patients were done retrospectively from the April 1, 1999 until June 30, 2002, i.e. for the
period of 39 months.

62
The criteria for enlistment
Diagnosis of agoraphobia with panic disorder according to MKCH-10 and DSM-1V /Smolik, 1996/
-Age of 18 - 65 years
-Disqualifying criteria
men and women older than 65 years of age
-depressive disorder
-schizophrenic disorder in anamnesis
-organic disorders
-mental retardation
-personality disorders
-addiction to alcohol and other addictive substances
-pregnancy
-serious somatic diseases

Aims
To compare application of psychopharmacotherapy after undergoing psychotherapy brief dynamic individual psychothe-
rapy /Group A/ with application of psychopharmacotherapy after undergoing ordinary psychiatric interview /Group B/.
To evaluate the results of the treatment in both groups of patients A and B /right after the treatment has been finished/.

Results
We included 23 patients suffering from agoraphobia with panic disorder, followed up at the out-patients psychiatric clinic
for 39 months in the study. Subgroup A comprised 8 patients, /women N = 3/, of the average age of 36.5 years, who underwent
brief dynamic individual psychotherapy and were taking psychopharmacotherapy continuously on average for 12.25 months.
After undergoing the psychotherapy, 6 patients have been without psychopharmacotherapy for 10.5 months on average and
only 2 patients continue their treatment by psychopharmacotherapy. These patients evaluated their current mental condition
with help of point scale for assessment of psychotherapy according to Kondas, 1988. The average number of points that they
reached was 55.6 points.
Subgroup B comprised 15 patients suffering from agoraphobia with a panic disorder that went only through ordinary psychia-
tric interview. The average age of patients was 41.06 years /women N=11/, they were taking psychophannacotherapy continuou-
sly for 25.94 months on average, while all of them except one /who has not been taking psychopharmacotherapy for 4 months/,
continue in taking psychopharmacotherapy. With help of the point scale for assessment of psychotherapy these patients re-
ached 50.1 points on average.
An important finding is that the patients who had gone through brief dynamic individual psychotherapy /while taking phar-
macotherapy/, were taking the psychopharmacotherapy on average for a shorter period /12.25 months in comparison with 25.94
months/ and with an exception of 2 patients, they did not have to keep taking the pharmacotherapy any longer. In the subgroup
B only one patient has been without pharmacotherapy.
As for shortcomings, it is a small number of patients in this study who had undergone a brief dynamic individual psychothe-
rapy, which we consider to be insufficient. The brief dynamic individual psychotherapy, which is highly demanding from both
time and finances point of view in the out-patients clinic conditions, seems to be in combination with psychopharmacotherapy
the most suitable combination at the treatment of agoraphobia with a panic disorder.
We consider using only one assessment scale of the psychotherapy with patients as another insufficiency of this work.
And, at last, it would certainly be useful to include also the economic result of applying the combined treatment of agorap-
hobia with a panic disorder.

Discussion
Term anxiety originates in Latin language - angere /depressed, constricted/ and anxietas /worry, discontent/. The nearest
meaning would be a feeling of an internal tension, expecting that something bad is going to happen, a feeling of undefined fear.
The psychiatric dimension of fear is also based on this description, and, according to Freud, it has a signalling function /
Kalicanin, 1996/.
One-sided application of psychotherapy, for example, results in reduction of anxiety and improvement of patients conditi-
on /Gillieron, 1990/. Nevertheless, even this procedure does not exclude additional psychopharmacotherapy /Bryois, 1994/. On
the other hand, a sole application of psychopharmacotherapy, for example of clomipramine for 8 weeks at the beginning of
treatment and then terminating it without a psychotherapy requires adding benzodiazepines to suppress anxiety. In the study
of the Swedish authors mentioned above, the benzodiazepines were added to 53 out of 62 patients who were included in the
study from the beginning. After 15 years of following up, only 10 out of the total number of patients were in remission, while
the number of patients taking benzodiazepines decreased to 10/18%/. However, the number of patients who at the beginning
did not take SSRI at all increased /0 patients at the beginning of the study/ to 15 patients /27%/ out of the whole group that have
completed the follow up /55 patients/ during the 15 years.
They were given alprazolam from benzodiazepines.

63
 Taking this biological approach to the treatment of patients we are also aware of certain deficiencies at long-term treatment.
Every patient is to be considered an individual, the treatment must be determined with the shortest possible time of taking the
drugs and with a view that after the treatment the patient will not be taking psychopharmacotherapy. It is important due to the
fact that even highly safe SSRI medicines have adverse effects /Briley, 2000/.
Adverse effects of SSRI appear by stimulation of 5 HT2-receptors /agitation, anxiety, panic attacks, insomnia, sexual dysfuncti-
on/ and 5HT3-receptors /nausea, gastrointestinal problems, diarrhoea, headaches /Briley, 2000, Suchopar, 1999/.
Other adverse effects of the treatment by SSRI are also known, such as extrapyramidal symptoms, more often acute then de-
ferred /tardive/ EPS; in spite of that the SSRI are safe at the long-term treatment provided that the indication and dosage are correct.
The most important aspect of all the advantages and disadvantages mentioned above for us was to enable the patient full re-
mission in the shortest possible time. That is why we chose for the patients who could come to the psychotherapy regularly the
brief dynamic individual psychotherapy in combination with psychopharmacotherapy. This method was more effective, which was
also proven in the tests carried out after the psychotherapy or ordinary psychiatric treatment.
Patients who underwent psychotherapy and psychopharmacotherapy - 6 do not take psychopharmacotherapy, whereas the
patients who came to ordinary psychiatric check-ups and had only ordinary psychiatric interview and took the psychopharma-
cotherapy still continue in taking the pharmacotherapy.
We would conclude the discussion by saying that SSRI affect impulsiveness, affective unstableness that are parts of the tempe-
rament while applying psychotherapy helps in approaching at objective relationships and self-assessment. Applying the combined
treatment in a neurobiological way could be crucial in the effectiveness of the treatment /Gabbard, 2000/.

Conclusion
Even with a small number of patients the combination of psychopharmacotherapy and psychotherapy proved to be the most
effective, bringing permanent remission without possible dependence on drugs as well as reducing the risk of adverse effects of
psychopharmacotherapy.

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tmatick kurz v psychoterapii,ILF,Bratislava, 22.5.-26.5.1989 (Pointing scale for evaluation of psychotherapy L.R.Tucker, modified
by Kondas, oral presentation, national thematic course in psychotherapy, ILF, Bratislava.)
Landowski J.,Lysiak-Szydlowska W.:Low plasma dopamine-b-hydroxylase activity in patients with panic disorder,Archives of
Psychiatry and Psychotherapy,1999,Vol.1,Dec.1999,pp.63-68.
Smol P.:Duevni a behaviorln poruchy,Maxdorf - Jesenius,1996,487,pp.243-299 (Mental and behavioural disorders)
Suchopr J.:Remedia,Compenditun, Tretie vydn,Panax, 1999,743,pp.180-222
Tadi N.:Psihoanalitika psihoterapija dece i mladih,Nauna knjiga,Beograd, 1992, 445,pp.395-403

CHART No. 1 - COMPARISON OF THE PERIOD OF USING PSYCHOPHARMACOTHERAPY AND THE

PERIOD WITHOUT PHARMACOTHERAPY AFTER HAVING UNDERGONE THE BRIEF DYNAMIC
INDIVIDUAL PSYCHOTHERAPY /GROUP A/ AND THE EVALUATION OF PSYCHOTHERAPY
ACOORDING TO KONDAS.
Assessment scale of psycho- Continual use of psychopha- Period in months Age in years Sex
therapy according to Kondas rmaco-therapy in months without psycho-pharma-
ceu-ticals
61 11 17 34 M
59 5 6 45 M
54 10 24 46 M
52 24 24 24 M
33 39 39 43 F

64
67 5 5 28 F
52 2 5 37 F
66 2 6 31 M
55.5 /average/ 12.25 /average/ 10.5 /average/ 36.5

CHART No. 2 - COMPARISON OF THE PERIOD OF USING PSYCHOPHARMACOTHERAPY AND THE

PERIOD WITHOUT PHARMACOTHERAPY AFTER HAVING UNDERGONE THE BRIEF DYNAMIC
INDIVIDUAL PSYCHOTHERAPY /GROUP B/ AND THE EVALUATION OF PSYCHOTITERAPY
ACOORDING TO KONDAS.
Assessment scale of Continual use of psycho- Period in months Age in years Sex
psycho-therapy according pharma-cotherapy in without psycho-
to Kondas months pharma-ceuticals
47 33 Using 49 F
54 20 Using 39 M
57 8 Using 39 F
34 32 Using 50 F
63 23 4 30 M
60 9 Using 36 F
33 32 Using 29 F
59 7 Using 59 F
40 30 Using 47 M
52 37 Using 43 F
61 32 Using 22 F
52 32 Using 40 F
46 28 Using 36 F
52 36 Using 41 M
32 30 Using 57 F
50.1 /average/ 25.94 /average/ 1 not using 41.06

CHART No. 3 - LIST OF THE PHARMACOTHERAPY OF PATIENTS WHO HAVE UNDERGONE

THE BRIEF DYNAMIC INDIVIDUAL PSYCHOTHERAPY /GROUP A/
Name of drug Number of patient
Paroxetinum+sulpiridum+clonazepamum 2
Paroxetinum+clonazepamum 2
Mirtazapinum 1
Venlafaxinum 1
Citalopramum+bromazepamum 1

Alprazolamum 1

CHART No. 4 - LIST OF THE PHARMACOTHERAPY OF PATIENTS WHO HAVE UNDERGONE

AN ORDINARY PSYCHIATRIC INTERVIEW /GROUP B/
Name of drug Number of patients
Paroxetinum+clonazepamum 10
Paroxetinum+clonazepamum+valproic acid+natrii valproas 1
Citalopramum+clonazepamum 1
Citalopramum+alprazolamum 1
Paroxetinum+hydroxizinum 1
Paroxetinum+valproic acid+natrii valproas 1

65
PHARMACOECONOMICS OF THE TREATMENT OF AGORAPHOBIA WITH
PANIC DISORDER

INTRODUCTION
Medication and medical aid costs, which reached total amount of 9,648 billion Sk (Slovak crowns) in 1999, represent second
most important item of the health care budget of the Slovak republic (SR).
During the same year, only diagnostic and therapeutic services, performed by contractual health institutions, have had
higher costs. In 1999, compared with previous year, medication and medical aid costs exceeded the budgetary plan for more
than 1,749 billion Sk, while average costs of a single medication package rose by 13 percent (VZP previous year budget, 2000).
According to annual report of Veobecn zdravotn poistovna Slovenskej republiky (VZP SR), by the end of 1999, average costs
of a single medication package reached amount of 140.5 Sk, although by the end of 1998 these costs represented only 117.1 SK
(Veobecn zdravotn poistovna, 1999). This development was, among other reasons, caused by increasing prescriptions of
modem antidepressants, which have higher institutional costs compared with classical preparations. However, modern antide-
pressants play a decisive role during the treatment of agoraphobia (Prako, 1999).
From epidemiological point of view, agoraphobia with panic disorder is one of the most frequent types of phobia. Total pre-
valence in average population reaches 5 percent, 3 - 5.2 percent in mens subgroup, and 1.8 - 23 percent in womens subgroup,
depending on their sociocultural environment (Starevi, 1997). Agoraphobia usually appears in the third decennium, affecting
active lives of patients, which is an important factor with regard to productivity of work and indirect costs.
In 1980, more than 2 million American citizens, of average age 37 years, suffered from agoraphobia with panic disorder and
some other anxiety disorders (Sheehan et al., 1980). Individuals, suffering from panic disorder, have seven times higher usage
of all medical services and a double number of inability to work periods, compared with average population (Siegel at al., 1990).
The field of anxiety disorders was until now rather forgotten by pharmacoeconomists, because a large number of people,
suffering from these diseases, do not visit psychiatric outpatient departments.
Frequently, general practitioners misdiagnose such patients as being somatically sick. These patients are then long-term,
unsuccessfully, and costly treated for their sickness (Hosk., 2000). In the computer database MEDLINE, there is only a mini-
mum of entries, dealing with pharmacoeconomics of agoraphobia. While searching, agoraphobia and cost keywords may
be used, possibly benefit, effectiveness, or utility. However, some older publications do not meet the criteria, required
for modern pharmacoeconomic studies. Above facts suggest, that the necessity to study economical aspect of agoraphobia
and its pharmacotherapy, within the frame of Slovak health service is urgent.
The main objective of our study was to determine the average daily and total pharmacotherapy costs of agoraphobia with
panic disorder when treated by non-psychiatrist outpatient practitioners, compared with accurate diagnostics and treatment
in psychiatric outpatient department. Average daily and total number of tablets, taken by patients during the examined peri-
od, was also analyzed.

66
THE EFFICACY OF DEPRESSION TREATMENT WITH M1LNACIPRAN (A
SIX- MONTH EXPERIENCE)

AUTHORS
Dana Ignjatoviov, M.D. (1)
Milan Ignjatovi, M.D. (2)
Silvia Beatriz Schweitzer, M.D. (3)

(1, 2) Private Psychiatric Outpatient Surgery, Cesta k nemocnici 1, Banska Bystrica, Slovak Republic
(3) Psychiatric Department, Cespedes, Buenos Aires, Argentina

Summary
Depression represents one of the most frequent and grave psychical alienations. It manifests itself by tiredness, troubles
with sleeping, headaches, loosing or putting on weight, and failure of sexual function. Bad mood, however, is not necessarily
the most dominant symptom [G.N. Christodoulou, 2002].
It means that together with the establishment of the right diagnosis it is very important to manage an adequate treatment
of depression. Some of the key points, not only in the conditions of outpatient treatment, are anamnesis exploration of previo-
us depressive episodes, family anarnnesis of affective diseases, and clinical exploration in relatives.
Depression today represents the 4th most frequent cause of health damage or loss of life due to early affection or morta-
lity. It is expected that depression will become the 2nd in 2020 [G.N.Christodoulou, 2002].
In the U.S. A., yearlong prevalency represents 12.9% in women and 7.7% in men [Kessler et al., 1994]. In Europe, prevalency
is 17% [Lepine et al., 1997].
Our 6-month follow-up included 12 patients using milnacipran 100 mg per day. We made evaluafions of HAMD and HAMA
at the start (it means on the first day of the follow-up) and used the CGI scale.
Two patients were discarded from our follow-up: one patient had discontinued the medication on her own in the 4th month
of the course of treatment and the other one was hospitalized due to a high risk of suicidal tendencies (HAMD-39 points, HAMA-
28 points).
We have evaluated HAMD on the first day of treatment, then one month later, and then half a year after the setting up of
milnacipran 100-mg per day. In the 2nd month we did not observe any kind of strong amelioration (HAMD-19.8 points), but in
the 6th month HAMD reached to 7.1 points.

Key words
Depression, HDRS (Hamilton Depression Rating Scale), CGI (Clinical Global Impression), milnacipran

SAMPLE GROUP AND METHOD

In the card files of the psychiatric outpatient department of this studys first author, all patients, suffering from ago-
raphobia with panic disorder for longer than two years, were selected, who were previously treated by other therapists
than psychiatrists. These patients later joined outpatient psychiatric care, which was carried out during nineteen nineties.
Agoraphobia was diagnosed according to DSM-IV classification (Kaplan et al., 1994). Patients with psychiatric comorbidity,
together with pregnant women, were excluded from the research.
Total number of evaluated individuals reached 28, 25 women and three men. Average age of the sample group members
was 41.5 years (from 20 to 62 years, S.D. = 11,4). Their average sickness period, before starting psychiatric treatment, was 10
years (from 2 to 30 years, S.D. = 7,0).
Patients were originally treated by outpatient general practitioners, internists, neurologists, and other non-psychiatric
specialists, usually without the prescription of psychopharmatics for relieving their physical disorders, for example vertigo,
back aches, intense heart beating, digestive tract disorders, and asthma. Prescribed were various types of analgesics, antiphlo-
gistics, vasodilatations, myorelaxants, vitamins, hormonal preparations, antiasthmatics, antimigraine drugs, or prokinetics.
Anxiolytics were used only exceptionally. None of the patients used antidepressive medication. When they began with
psychiatric treatment, being correctly diagnosed as suffering from agoraphobia with panic disorder, majority of previous
medications were discontinued and replaced by psychopharmatics. Thirteen patients then took paroxetine in combination
with clonazepam, six patients were treated with paroxetine intermittently with sulpirid and clonazepam, one patient took
paroxetine in monotherapy. Five patients were treated with citalopram in combination with sulpirid or clonazepam, one pa-
tient took citalopram in monotherapy. One group member was treated with fluoxetine only and another with dosulepin.
Outpatient psychiatric treatment then comprised supporting
psychotherapy. During the examination period, none of the patients was hospitalized in the psychiatric department.
Outpatient psychiatric treatment was monitored for the period of one year. Then, patients subjectively evaluated its effec-
tiveness. Clinical conditions of twelve patients were dramatically improved (absence of panic attacks, agoraphobic beha-
vior, or anticipation anxiety), ten patients have improved (reduced number of panic attacks, decline of agoraphobic symp-
toms and anticipation anxieties), four patients reported no progress (remaining panic attacks with constant frequency and

67
intensity), while conditions of only two patients worsened. On the basis of these facts, psychiatric treatment can be, as a
whole, considered successful.
Pharmacotherapy costs were evaluated in reverse, using the open method, from the medical records of the psychiatric
outpatient department and other outpatient departments of previous specialists. Defined daily doses (DDD) of medicati-
ons, according to Suchopr (1999), were taken into account. Prices were calculated in Czech crowns (K), because prices in
Slovak crowns change frequently, with regard to changes in the classification of drugs in the Slovak republic. For example,
DDD of paroxetine (20 mg) was 34.3 K, citalopram (20 mg) 32.4 K, fluoxetine (20 mg) 44.0 K, clonazepam (2 mg) 3.6 K
and sulpirid (100 mg) 8.7 K.
Study was not subrnitted for the approval of the ethics commission, as it was a retrospective examination of medical re-
cords, without the participation of patients, or any influence on their treatment. For statistical processing of acquired data,
NCSS 2000 computer software was used. Distribution normality of acquired values, relating to individual variables, was eva-
luated using Shapiro-Wilks and Kolmogorov-Smirnov tests. However, because the distribution was abnormal, statistical si-
gnificance of differences, relating to measured values, was examined by Wilcoxon nonparametric test.

RESULTS
Results are stated in the table 1. Although the average daily price of pharmacotherapy was higher in the case of psychia-
tric treatment of the psychic disorder, average total medication costs were lower, compared with treatment carried out by
practitioners-nonpsychiatrists. Significantly lower were also average numbers of tablets prescribed by psychiatrists, oppo-
site to previous medical treatment, whether their daily or total amount was examined. All described differences are stati-
stically highly significant.

DISCUSSION
To illustrate the problem in more detail, one casuistic example can be depicted: Forty-seven years old women, ill, married,
educated as a waitress, currently unemployed, was originally treated for ten years by the internist and neurologist for ver-
tigo, intense heart beating, breathing problems, pain, tingling of limbs, fear from falling, and loss of self-control. Difficulties
occurred during the attacks with frequency of four times monthly, sometimes more often. Diagnostic conclusion was ver-
tebrogenic algesic syndrome vertigo and hypertension. Isradipin, enalapril, bromazepam, betahistin, tokoferol, cinnarizin,
diklofenak, and metamizol were prescribed gradually. During this period, she had taken 72,000 tablets in total price of 251,209
K, however, her treatment was ineffective. She was then diagnosed in the outpatient psychiatric department with diagnosis
agoraphobia with panic disorder. Pharmacotherapy was changed to paroxetine, clonazepam, enalapril, and isradipin. During
one year of psychiatric treatment at the outpatient psychiatric department, 2,520 tablets were prescribed in total price of
8,209 K. According to patients subjective assessment, there has been a gradual decrease of panic attacks frequency and a
moderation of anticipation anxiety in such an extent, that she was able to start working again.
When treating agoraphobia with panic disorder, SSRI (selective serotonin reuptake inhibitors) antidepressants are used
more and more frequently (Prako, 1999). This type of treatment is expensive, when considering daily-prescribed dose,
however, it generates savings compared with previous long-term unsuccessful therapy, performed by general practitio-
ners and some non- psychiatric specialist without the usage of psychopharmatics. When health insurance agencies evalua-
te and reduce financial costs of prescriptions in psychiatric outpatient department, they should, at the same time, take into
consideration the long-term costs of psychic disorders treatment, including all pharmacotherapy prescribed by speciali-
sts-nonpsychiatrists for the same patient. Only then, it is possible to objectively prove, which treatment is expensive and
which, on the contrary, saves finances.
This study did not examine the quality of patients lives. Nevertheless, there are serious doubts about the satisfactory
quality of life, when symptoms of anxiety disorder are not properly treated for several years, and additionally, patient is en-
cumbered by taking thousand of tablets of various medications, especially when considering their negative effects.
Our results are in accordance with international studies, which deal with similar problems. Greenberg et al. (1999) have
assessed total yearly economic costs of anxiety disorders in the United States of America from the viewpoint of the who-
le society. In 1990, these costs reached 42.3 billion dollars. 54 percent of these costs represented health care costs outside
the field of psychiatry. The highest costs were found for patients suffering from post-traumatic stress disorders and panic
disorders. Majority of these costs could be reduced by early diagnostics of the disease and its proper psychiatric treatment.
According to the results obtained by Reese et al. (1998), patients with panic attacks statistically and notably seek out the
health care more outside the field of psychiatry, compared with patients suffering from social phobia, or psychically he-
althy individuals. This brings about increased direct medical costs, which could be, again, reduced by proper diagnostics and
psychiatric treatment of the disorder.
General practitioners, internists, and neurologists should be informed in more detail about the symptoms of agoraphobia
with panic disorder, so that proper diagnosis can be determined early, patients being immediately transferred for psychia-
tric treatment. This would lead to the reduction of total medication costs and suffering of patients.
Further studies, dealing with this problem, should also comprise the evaluation of direct costs resulting from the peri-
odical medical examinations and treatment. Monitoring of indirect costs, when treating agoraphobia with panic disorder,
would be appropriate especially for those costs, which are the result of the inability to work and the decrease of work pro-
ductivity of affected individuals.

68
CONSLUSION
Results of this study prove the lack of economy and ineffectiveness of agoraphobia with panic disorder treatment in
outpatient departments of non-psychiatric specialists in the Slovak Republic. Proper diagnostics and psychiatric treatment
results not only in improvements of clinical state of patients, but also in savings of total direct treatment costs of pharma-
cotherapy. Considering historically recent division of the common state of Czechs and Slovaks, authors presume that acqu-
ired results can be applied also for the Czech Republic.

69
CRISES PERIODS IN THE TREATMENT OF ALCOHOLISM ADDICTION
SYNDROM IN PSYCHIATRIC MEDICAL OFFICE

AUTHORS
MUDr. Milan Ignjatovi, Psychiatric Medical Office, Health Care Center, Bansk Bystrica
MUDr. Dana Ignjatoviov, Psychiatric Department, F. D. Roosevelts Hospital, Bansk Bystrica

SUMMARY
We found out by multimodal or complex way of patients treatment in alcoholism addiction syndrome that there is a pe-
riod of crisis in the limited period of 18 months.
Crises periods are expressed by greater amount of non-abstinent patients and patients, who broke abstinence mostly in the
first month of outpatient treatment but also in the first month after inpatient treatment.
Crises periods of patients are inflicted by psychological motivational factors if psychotherapy has less influence on their ab-
stinence, and it seems to us that the supporting psychopharmacotherapy has the lowest influence.

KEY WORDS
alcoholism addiction syndrome
multimodal treatment
motivational factors
psychotherapy
psychopharmacotherapy

INTRODUCTION
Even if we knew that addictions as such belong to contra-indication for short-time individual deeply oriented psychothe-
rapy, we tried to support patients treatment by individual as well as group psychotherapy, eventually by family and marital
psychotherapy.
On the first time we examined 27 patients in our medical office, the others have already been treated in another medical
offices including Alcoholism Addiction Office, as well as hospitalized and frequently inpatient treated - see table 4.
According to the authors who are longer concerned of psychotherapy of patients treated for alcoholism addiction syndro-
me, the object of their interest were patients traumatic experience from their childhood and therapeutic alliance.
To the dynamic oriented therapy they added behavioral therapy as well as others. None of them list exactly only the way of
medicamentous treatment or by psychotherapy, or especially by one or another kind of therapy.
All of them agree that the therapy should be complex and long-term. There are known some cases of controlled drinking
but its rate is very low (1 %, Skla).
We could not accept this alternative, and so 10 patients from groups continued in drinking.
Sociotherapeutic groups as an important part of long-term treatment for alcoholism addiction syndrom can be seen in the
studies of Czech and Yugoslav authors as plumbless facts.
We did not practice any reinforcing treatment (repeatings) in our medical of but to offer this possibility to the patients in
outpatient conditions, we allowed them to report in the medical office more often during their crisis time.
Reinforcing treatment is also meaningful psychologic medium for patient, and its advantages describe Nbelek and Vongrej
in their study.

GOAL
To obtain information after what periods the patients experience psychic crisis during multimodal or complex treatment
for alcoholism addiction syndrome.

METHODOLOGY AND GROUP OF PATIENTS

We used the same way of treatment for all the patients who came to our medical office, including short-time individual dee-
ply oriented psychotherapy (hereinafter as SIDOP) with the first interview. After the first sitting we made the contract with the
patient: in the first month we will meet once a week to have psychotherapeutic conversation lasting 50 minutes, in the second
and third month once in 15 days, i. e. 8 sittings in 3 months and only once a month afterward.
Patients received supporting medicamentous treatment based on abstinence or another symptomatology lasting at least 3
months, what was also the part of therapeutic contract.
We did not make any difference between patients examined first time in our medical office and patients treated in other
specialistic medical offices or departments.
We made the same contract with each of the patients.
To the group of patients belonged 55 patients for the period of 18 months.

70
 The part of contract was also the fact that after break-in of abstinence (any patient froth this group) we send him to the in-
patient treatment lasting 3 months and if it is rejected, we recommend him to another psychiatrist, because the patient would
not benefit from the therapeutic alliance in this case.
Patients were recommended after 3 months of outpatient treatment to the sociotherapeutic groups (sittings), which took
place once a month in medical office. As an alternative in the patients treatment we accepted only permanent and consistent
abstinence what was monitored by every individual visit of patient in medical office by toxicologic examination of alcohol pre-
sence in urine.
All the patients involved in the study belonged to gama and delta alcoholism type.
There were 55 patients in the group, 7 women and 48 men, see table 1. The average age of patients was 44,87 years.
Socioeconomic status: 45 patients were employed, 7 were unemployed, 3 were pensioners, see table 2.
Education structure: 47 patients finished Specialized secondary school, 3 of them Secondary Grammar School, 5 patients
finished University, see table 3.

RESULTS
We had 11 relapses in outpatient treatment and 7 relapses after inpatient treatment, see table 5.
Crises periods for patients after inpatient treatment were: first month, when 5 patients relapsed, fourth month, when 1 pa-
tient relapsed, eighth month, when also 1 patient relapsed.
The number of relapses after outpatient treatment is a bit higher, and crises months were close to each other again: in the
first month 7 patients relapsed, in the third month 1 patient relapsed, in the fourth month 1 patient relapsed, in the ninth month
2 patients relapsed, see table 6.
The adherence or breach of the contract did not substantially influence the abstinence of patients.
The number of patients who did not break the contract and are abstainers is 23. Remaining 22 patients broke the contract
but are abstainers. Of course, we included possible relapse into our contract as well as the next procedure in this case, so the
inscribed relapses were throughout 18 months. Abstinence with adherence or breach of contract was sometimes interrupted
by relapse.
Group therapy, evaluated after 18 months of outpatient treatment, was also involved.
The number of patients who abstained and went to group therapy was smaller than the number of patients who abstained
without group therapy (sociotherapeutic groups), see table 8.
Crises periods expressed in number of patients were the most significant in the first month in both inpatient and outpati-
ent treatment.
The inpatient valuation was realized from July 1, 1997 to December 31, 1998, and only patients breaching the contract were
taken into consideration, even though they relapsed and we quantificated their abstinence in a statistical way.
Those, who abstain 15 days before the end of eighteenth month from the base line of the project, take the first place. They
are followed by patients abstaining 30 60, 90 days, 4, 6, 9 and 12 months to 18 months.
Four patients abstained 18 months, five patients abstained 12 months, four patients abstained 9 months, four patients ab-
stained 6 months, five 90 days, four 60 days and three patients abstained 30 days, see table 9.
Exactly those numbers show the periods that can be crises, which patients must overcome, many times by their self-motion.
We managed the SSRI therapy as a monotherapy of Antabuson, non-benzodiazepin anxiolytics, antipsychotics, tymopro-
fylactics, nootropics and very rare of benzodiazepins.
In SSRI therapy the most frequent drugs were citalopram, from the group of non-benzodiazepin was managed anxiolytics
hydroxizin. The pharmaceutical therapy even when used in monotherapy or in combined therapy (with another pharmaceuti-
cals) did not have much influence on patients decision whether to abstain or not, see table 10.

DISCUSSION
Statistical results and also basis of unbroken therapeutic contract made us to realize that even if we offer multimodal way
of treatment for patient, patients attitude is the main part of successful treatment.
This also shows the difference between those, who did not breach the contract and abstain and those, who did but abstain
as well; it is a minimum of 1 patients difference.
Neither the sociotherapeutic groups influenced patients abstinence that much, because 19 patients joined the associated
therapy and they abstain, the other 26 patients abstained without the supporting associated therapy.
Upon relapses we found out that patients in the first month of outpatient treatment or in the first month after inpatient
treatment experience very strong crises periods. In this case number of relapses is the highest.
Regarding psychopharmacotherapy, its highest effect is in abstinence symptomathology. The drugs from SSRI group (cita-
lopram) had good influence on patients affecting their impulsivity.
By the end of the year 1998 we finished the study with all the patients including those who abstain only 15 days. Statistical
results show that the highest number of abstainers is in the 1st, 2nd, 3rd 6th, 9th, 12th, and 18th month.
These months are psychologically very important for patients. During the periods between these months it is possible the
abstinence will be interrupted - patients noted this fact at the psychotherapeutics conversations. They stayed or would stay
without drinking for a few months (e. g. 3, 6,...), that is why we call those periods crises periods, after them the relief, carele-
ssness, control lose may come, and so the patient might relapse again.

71
 The patient has to intensify the contact with his therapy specialist during this period of time or to start attending the soci-
otherapeutic groups regularly.
All that has been said are our wishes. But patients rather choose another self-treatment, in which self-motivation can
be involved.
When we realize that only as much as patient wants can be done, and if we know months during which the crisis may occu-
re, we can contact him and support his abstinence struggle.
As a main factor of good outpatient treatment of patients alcoholism addiction we accept the motivation and relatively
good social integrity of patients as well as qualitative therapeutic relation.

CONCLUSION
After multimodal of complex way of patients treatment in acoholism addiction syndrom we found out that there exist cri-
ses periods in the limited period of 18 months.
Crises periods are expressed by greater amount of non-abstinent patients, who broke abstinence mostly in the first month
of outpatient treatment but also in the first month after inpatient treatment.
Crises periods of patients are conditioned by psychological motivational factors if psychotherapy has less influence on their
abstinence, and it seems to us that the supporting psychopharmacotherapy has the lowest influence.

BIBLIOGRAPHY
Doc. MUDr. Jaroslav Skal a kol.: Zvislost na alkohole a jinch drogch.
I.ucha, T. aplov: K meta-psychopatolgii zvislosti (AD, 33-1998/1).
L. Kubika, L. Csmy: Prvn zkuenosti s eskou verz EuropASI (AD, 32-1997/4).
K. Nepor, L. Csmy: Souvislosti mezi alkoholem a jinmi nvykovmi ltkami, dusledky pro prevenci i lbu (AD. 32-1997/4).
H. Vos, L. Bos (Eds.): Narozen, zlomen a scelen. (Primrn vztahy, trauma a zvislost), (AD, 324 997/4).
M. Galanter: Model komplexn terapie zvislosti pro benou praxi (Network Therapy for Addiction: A Model for office. Practice,
AmJ. Psychiatry 150, 1993, 1, s. 28-36
J. Vongrej, L. Nbelek, D. Krajrova, I. ajgalkov: Vplyv opakovanej lieby na prevenciu recidvy alkoholizmu (AD, 33-1998/2).

Table 1 - Patients devided according to sex

Men Woman
Number % Number %
48 87,27 7 12,73

Table 2 - Socioeconomic status

Number %
Employed 45 81,82
Unemployed 7 12,73
Pensioners 3 5,45
Total 55 100

Table 3 - Educational structure

Number %
Specialized secondary school 47 85,45
Secondary Grammar School 3 5,45
University 5 9,09
Total 55 100

Table 4.- Patients already treated in other department, PAL inpatient treatment, psychiatric outpatients

Number %
Patients already treated in psychiatric medical office 1 1,82

72
Patients already treated in the Psychiatric department 19 34,55
Repeated PAL inpatients 2 3,64
PAL inpatients+outpatients 4 7,27
Patients treated in other department Department of 2 3,64
Internal Medicine
The others 27 49,09
Total 55 100

Table 5 - The number of relapses after inpatient and outpatient treatment

Number %
Relapse after inpatient treatment 7 12,73
Relapse after outpatient treatment 11 20,00
Others 37 67,27
Total 55 100

Table 6 - Relapses after inpatient and outpatient treatment in noted months (the number of patients)

Month
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

The number
of relapses
after 5 1 1
inpatients
treatment

The number
of relapses
after 7 1 1 2
outpatient
treatment

Table 7 - Patients divided according to contract and abstinence by the end of the 18th month

Number %
Adherence of contract, patient abstains 23 41,82
Breach of contact, patient abstains 22 40,00
Breach of contract, patient does not 10 18,18
abstain
Total 55 100

Table 8 - Patients divided according to group therapy and abstinence by the end of the 18th month

Number %
Group therapy, patient abstains 19 34,55
Group therapy, patient does not 0 0
abstain
Without group therapy, patient 26 47,27
abstains
Total 10 18,18
55 100

73
 Table 9 - Crises periods in patients abstinence (abstinence evaluation during the period of 18 months)

Total

Period of
15 30 45 60 75 90
abstinence 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
days days days days days days
(months)

Number of
1 3 1 4 2 5 2 1 4 0 3 4 2 3 5 0 1 0 0 0 4 45
abstainers

Others 10

% 1,82 5,45 1,82 7,27 3,64 9,09 3,64 1,82 7,27 0 5,45 7,27 3,64 5,45 9,09 0 1,82 0 0 0 7,27 81,82 18,18 100

Table 10 - List of psychopharmacotherapy

Disulfi-
Citalopramum ramum

Drugs

M F M F M F M F M F M F M F M F M F M F M F M F M F

Monotherapy 5 0

Combined 4 0
Therapy

M male, F - female

74
AGORAPHOBIA WITH PANIC DISORDER FAMILY
PSYCHOPHARMACOTHERAPY BY PAROXETIN

AUTHORS
Milan Ignjatovi, MD, Psychiatric Medical Office, Health Care Center, Bansk Bystrica
MUDr. Dana Ignjatoviov, Psychiatric Department, F. D. Roosevelts Hospital, Bansk Bystrica

SUMMARY
4 women - 55-year-old mother and her two daughters: 38 and 34 years old and one stepdaughter 20 year old were followed
and used in casuistics.
To make good quality family anamnesis is very important for risks family factors and for detection of psychical disorders.
The ways of heredity are: polygenic model, model of the dominant gene with incomplete penetration, autosomal dominant
model and the others.
There are many genetic hypothesis about genesis of the psychical disorders and genetics markers like: yohimbin, clonidin,
coffein, infusion of natrium lactatum, hyperventilation, L-tryptofan, benzodiazepins receptors, continuity between mitral prolaps
and panic disorder, positive response on antidepressants, personality studies of the patients with panic disorder (Eri Lj., 1991).
The problem is that patients didnt know about their disorder, about treatment, etiology, complications and consequences.
Treatment by psychopharmacotherapy confirms some of genetic hypothesis connected with correct diagnosis.
These 4 women were diagnosticated and adequately treated in our Psychiatric Medical Office, Health Care Center.

KEY WORDS
Agoraphobia with panic disorder, paroxetinun, genetic studies

INTRODUCTION
Long time ago, in the past century, when genetic research was not carried out, Beard wrote about consequent predispo-
sition for the occurrence and development of neurasteny.
Freud came up with similar experience and he pointed out the fact that neurosis of fright has the same symptoms among
several family members. Oppenheimer and Rothshild found out that family history of neurosis existed among 45% of observed
World War I soldiers who were diagnosed with Da Costa syndrome. Some time later, during the World War II, Wood found po-
sitive family history among 25% patients treated on heart neurosis.
Subsequent researches showed that panic disorder is a disease, which cumulates in the family.

METHODOLOGY AND GROUP OF PATIENTS

4 female patients were chosen for the casuistic study on the basis of 5 including criteria: 1. Biographical anamnesis, 2. Forgoing
diagnosis, 3. Current diagnosis, 4. Therapy, 5. Family relationship.
Observation and evaluation of results was carried out from October 1999 to March 2000, while all of the female patients
continue with the therapy and they are registered in our medical office.

OBSERVATION
The results are based on retrospective clinical observation of patients medical records where the focus was on the bio-
graphical anamnesis, diagnosis, therapy and family relationship.
The core of the study is formed by 4 casuistic cases which draw the importance of genetic factors for the occurrence and
development of panic disorder.
CASUISTIC No. 1
55 years old woman, worker, mother of three daughters, long term treated in different medical offices with diagnosis of
neurasteny. She visited our medical office on the recommendation of both of her daughters. She describes her first panic
attack as the situation when she had her middle daughter and she couldnt go for a walk with the buggy (in the year 1966), she
was dizzy and weak, she couldnt take anything into her hands, she had palpitations, was stifled, sweated, had pins and need-
les in her hands, felt a node in her throat and she helped herself by giving snow on her head. Afterwards she was scared to go
for a walk. Physicians prescribed chlordiazepoxidum (Radepur) and ergotamini tartas, belladonnae radicis, phenobarbitalum
(Bellaspon) for her and symptoms were gone for one or two days. Her husband didnt believe her that she was ill and he was
furious of her status. That all enhanced her tension and the patient was not even able to stand up from her bed because of the
dizziness. She was scared to visit a physician in the psychiatry ward at that time. First time she visited psychiatric medical office
in Brezno 20 years ago, she was taking chlordiazepoxidurn (Elenium), ergotamine tartas, belladone radicis, phenobarbitalum
(Bellaspon) and diazepanum (Seduxen). When her youngest daughter was born, she felt quite well during the daytime but she
got an attack after night shift. She described the attack like is: she woke up in the night, didnt know where she was, what she
was doing, she was steamy and very afraid. When her husband was close to her, she composed herself but in spite of this she
was not able to leave the bed.

75
 She had to be very responsible in her job, millions were at stake, fortunately nothing happened.
She was treated in the spa town of Vyn Rubachy since 1992. She felt very well in the baths because it was a peaceful pla-
ce. She was sent to visit a primary doctor 5 years ago who prescribed alprazolam (Neurol) and fluoxetinum (Prozac) for her.
She felt better, even though she still used to have panic attacks which were more mild and weaker. She concluded the combi-
nation of noted drugs because her physician changed one drug to fluoxetinum (Deprex).
She had strong diarrhea, strong headache and she felt sick after using this drug. The patient visited our medical office on
December 12, 1999 with no psychopharmacological medieation. We prescribed the medication of paroxetinum and clonaze-
pamum for her. The patients status improved very quickly (in 2 weeks time), she didnt have any attacks any more, her mood
brightened, she slept all the night, and she hasnt been scared of people any more. After one month the dermatologist diagno-
sed her with allergy to paroxetinum. Thats why this drug was replaced by citalopramum. The patient canceled the medication
of citalopram by herself and on the recommendation of her three daughters she started taking paroxetinum and clonazepamum
during the last control visit on the March 16, 2000. No allergy to paroxetinum occurs at present and previous allergic reactions
are thought to be possible comorbidity with allergy e.g. to another drugs or food. The patient evaluates her status as excellent
and she assesses the current therapy as the most sufficient and the most successful in 30 years of treatment.

CASUISTIC No. 2
38 years old female patient, single, lives with her partner who is addicted to alcohol and is aggressive when drunk. Currently
the patient tries to evacuate him from her flat a legal way.
The patient was treated by psychiatrist for a long time. She was not satisfied with the treatment and thats why she visited
our medical office on other patients recommendation.
The memories of her childhood are connected to her mother who lived with the children
alone, she was divorced, she raised the children quite strictly. The patients father drank a lot of alcohol, she remembers
that he even attacked them with a gun and he threatened to shoot them all. Her mother was very sick, she moved to her gran-
dmother and she got married for the second time. The patient couldnt sit down under the facts she underwent in her childhood.
When she cut adrift she got a flat and she took an alcoholic man to her flat. She wants to get him away in a legal way now.
When the patient visited our medical office for the first time, she had the following symptoms: palpitation, exudation, fear that
disallowed her to go to the work, trepidation of hands, she had as well as her mother a node in the throat. She got the first
attack in 1994 at home, she didnt know what that was, she felt worse and worse. Her status was so bad, that she couldnt even
watch TV, she was even scared of the people in TV shows.
Her mother had similar symptoms. She felt a noise in her head, she had to go to bed, couldnt go for a shopping to the mo-
les where a lot of people are. She stayed in the bed very often and didnt talk to people. One psychiatrist prescribed chlordiaze-
poxidum (Defobin) for her. When she didnt get enough, she visited another psychiatrist, who gave her maprotilinum (Ludiomil),
alprazolamum (Neural). In spite of that she had to call the emergency very often or had to visit the emergency by herself, she
got hypertension, couldnt compose herself. We registered her: with the .diagnosis of neurasteny and put her on paroxetinum
and clonazepamum right after her first visit in our medical office. Between the first and the second week her health status im-
proved, attacks receded, she started to go for .a shopping, wasnt scared of people anymore. She also attended the group the-
rapy in our medical office. When she started to have conflicts with her partner, her health status got worse. The patient recei-
ved shoots of progesterone and estradioli benzoas from the year 1980 because sometimes she didnt have menstruation up to
3 months. Since she has been treated by paroxetinum, her menstruation is periodical. Meanwhile the patient received the ver-
dict which states that her partner has to move from her flat. The patient is looking for a new job because nobody believed in
her invisible illnesses in her former job. She evaluates her status as good, stabilized and the treatment as successful.

CASUISTIC No. 3
34 years old female patient, previously unemployed, married. For the first time she got palpitation after the wedding in 1986.
She couldnt breathe and her health status started to worsen after 3 years. She started to feel sicker since she became unem-
ployed. Since she finished only elementary school, she studied at the school for waiters but in fact she had stage fright and was
very self-centered, she didnt finish the school for waiters. She doesnt remember her father because her parents got divorced
when she was 4 years old. She describes her symptoms as weakness, shakiness, vertigo, chest pains, shaking of her legs. She
feels better when she stays at home in silence. Her husband drinks alcohol and when drunk, he upbraids her the fact that she
is unemployed. She adds to her symptoms that she couldnt breathe; she felt the way she would suffocate. These symptoms
appeared when her daughter, who had legs desjointedness and didnt sleep at night, was born. That was a huge endurance for
her. When the patient tended her daughter to the school, she felt she wouldnt return home and would vomit. There were more
panic attacks upraised during one week and she felt she would get heart attack. When she worked as a cleaner in an elementary
school, she felt good in a collective of colleges. She felt the worst when she had to stay at home alone. She underwent diffe-
rent medical examinations but nothing was found. Afterwards she started to be scared of people and thats why she didnt go
abroad (she didnt travel by bus, didnt go for a shopping). There is comfort at home, its worse when the husband gets drunk
and offends her. The neurologist put her on paroxetimun. Even though her health status improved, the patient stopped the
treatment by herself because the period of menstruation shortened up to 15 days.
The patient was examined in our medical office for the first time on the recommendation of her mother and two sisters in
February and she had the following symptoms: hands shakiness, enhancing anxiety, node in the throat, she was scared of going
outside, felt better at home.

76
 After the introductory interview we agreed on the therapy of paroxetinurn and clonazepamum.
After one month the patient notes that her health status improved, she has no panic attacks, she meets people and she eva-
luates the treatment as the best one so far.

CASUISTIC No. 4
20 years old female patient, trained tailor, the youngest one in the proximity. After the childbirth in 1988 she began to have
vertigo, palpitation, body shakiness and was scared of going out for a shopping. She had these attacks more than 4 times a month.
Unlike her mother and stepsisters, she didnt have a node in her throat. When she restored from the smallpox in her childhood,
she was diagnosed with the epilepsy. The patient states that she used to faint, she sensed everything around but couldnt res-
pond. She visited a neurologist who put her on phenytoinum and carbamazepinum. Then the pediatric neurologist put her on
natrium valproate when she was 12 years old. Gradually acidum valproicum + natrii vaiproas (Depakine Chrono 500) of a dose
of 1 tablet in the morning - 1 tablet in the noon- 1 tablet in the evening were added to the therapy management. Phenytoinum
was rejected, natrium vaiproat (Orfiril 300 mg in one tablet) of a dose of 1 tablet in the morning - no tablet in the noon - 1 ta-
blet in the evening was kept. When the patient attended the 7th grade of the elementary school, she had vertigo during the le-
ssons, she asked for going to the toilet very often and she felt very badly during the biology classes when they learned about
blood. She was hospitalized during that period of time. When medical staff told her about the blood sample testing, she fainted.
She was scared of going to school, her classmates laugh at her because of her epilepsy and she didnt remember anything after
each attack. At home the attacks started to appear during the night. She got shakiness and her mother had to wake her up. She
had vertigo in the classroom very often. Moreover she fainted and fell down at home. She used to faint more often in school,
especially in the period of examinations; she fainted more often at home as well at that time. She has never had enuresis and
has never bitten her tongue. The epileptic attack lasts for 1 minute and she has never slept after the injection of diazeparnurn
or after the attack. When she got very painful menstruation, she felt she would suffocate and they called the ambulance imme-
diately. The patient had no attacks at the secondary school. No attacks were present at home at that time either. She visited a
pediatric neurologist for the first time when she was 11, panic attacks uprose when she was 12 years old. Even though she was
taking phenytoinum and carbamazepinmu, she fainted at home as well as at school. She felt badly all the time.
Suddenly, the attacks were gone when she was in the 8th grade of the elementary school.
Palpitation appeared at home when she was 12 years old, she didnt tell her parents about it, she just retired to her room
and went to bed. She lists more exact medication since her age of 16, when she received natrium valproas (Orfiril 300 mg in
each tablet) in a dose of 1 tablet inthe morning - no tablet in the noon - 1 tablet in the evening. When she was 18 years old she
was taking acidum valproicum + natrii valproas (Depakine Chrono 500) in a dose of 1 table in the morning - 1 tablet in the noon
- 1 tablet in the evening. The attack uprose in the dormitory when she was 16 years old. It was seldom and as she states further,
there have been no more attacks at home or at secondary school.
She got married at the age of 18; she gave birth to a daughter in 1983 and 3 days after the childbirth, she fainted lying in the
bed. When she rinsed pampers or when she woke up to get pills, the attacks returned. She got aura and consequently fa-
inted when she saw the strips on the tiles. Prolonged observation of the blue strips on the tiles provoked this kind of schism.
After that accident her mother didnt let her staying at home alone, she was with her daughter even when she was having a
shower. To help herself, the patient doesnt look at those strips when she is in the bathroom. When her oldest sister remembe-
red the incidents with the bathroom, we found out that she used to lock the patient in the bathroom as a punishment when she
behaved badly in her childhood. She haunted the patient to leave her inside the bathroom for good in this time of her childho-
od. This fact was confirmed also by the middle sister. The patient is 20 years old now, last time she fainted in maternity hospi-
tal one year ago. Approximately half year after her child was born she began to have vertigo, uncertain walking, everything was
spinning around her, she sweated. These feelings attacked her 4 times a month. Since the patient milked her child, her health
status worsened during each menstruation period. She visited our medical office on the recommendation of her stepsister on
the November 3, 1999. Het stepsister suggested her to visit the psychiatrist for a long time.
The patients status improved after two weeks of medication of paroxetinum and clonazepamum, she has had no more anxi-
ety nor panic attacks. Whereas the patient is listed in neurological office, we mutually consulted the therapy and recommended
to reduce eventually to cancel their therapy. After the arrangement we stopped the management of natrium valproas (Orfiril),
we reduced the dose of acidum valproicum + natrium valproas (Depaldne Chrono 500) up to 1/2 tablet in the morning - no ta-
blet in the noon - 1 tablet in the evening. Patient feels good, the health status is stabilized, she takes care of her daughter with
joy, handles with common activities without any problems, she evaluates the treatment as being successful.
Each of these 4 patients evaluated the treatment of their mothers, sister and stepsister separately, so besides subjective
evaluation we have heteroanamnestic (heterologic history) evaluations as well.

SUMMARY
4 women, a mother and 3 daughters who were chosen according to 5 including criteria are inncluded in the casuistic study,
whereas 2 sisters were their own, one was a stepsister. The average age was 36,75 years. Symptoms were present in average of
16,25 years and treatment in our medical office lasted 3 months in average.There has been used paroxetinum in a dose of 30 mg
per day and clonazepamum in a dose of 0,5 up to 1,5 mg per day individually in the treatment.
The results were analyzed on the basis of patients subjective evaluation as well as according to the heteroanamnestic evaluation.

77
DISCUSSION
Family studies and studies realized on twins who suffer from anxiety and panic attacks show that panic disorder is familiar disease.
However, family cumulation is neither sufficient nor necessary condition to confirm that the disorder is congenital. It is necessary to
look through the exact pathway of genetic transmission, but we have not reached definitive conclusion up to now. There are several
models available: polygenous model, model of dominant gene with incomplete penetration, autozom dominant model. The results of
the researches done up to now show that the model of dominant gene with incomplete penetration is the most feasible way of gene-
sis and development of panic disorder, but the model of polygenous heredity is also not definitely rejected. We have investigated the
model of polygenous autozom dominant heredity in our study. The results we have reached suggest that panic disorder is transmitted
as an autozom dominant disorder (1). Family studies of the panic disorder realized in 1980s show that the risk of uprise is 17,3% in first
grade relatives and added risk from 7,4% for possible panic disorder (which uprises with 2,3 rarely with 4 symptoms of the panic dis-
order criteria).
Some authors have found out high risk of panic disorder in both groups of relatives in a case of panic disorder (17,3%) and in gro-
ups of relatives in a case of agoraphobia (8,3%), compared to 4,2% in control group. (2)
Other studies found out from 4 to 8 higher risk of panic disorder in the group of first grade relatives of patients with panic disorder
diagnosis compared to first grade relatives of patients with other psychical disorders. (3)
Having gone through the all aspects of genetic research of anxiety and panic disorder, the problem how to explain them still remains.
In spite of evidences that panic disorder is family disease, as well as there is high concordance in monozygote twins, pathophysio-
logical mechanisms of panic disorder development have been determined. We dont have sufficient feasibility to define the role of ge-
netic factors in panic disorder etiology for certainty.
What is really proved is the fact that anxiety and panic disorder are not inherited by the simple principle of Mendelejev heredity
rules. It is proved that a lot of anxious conditions occur in the participation of psychological, social and cultural factors without the vi-
sible contribution of genetic factors.
There is a model of possible panic disorder uprise and development, in which the biological, psychological and social factors are
comprehensively present and the model is based on those proved facts.
Truly, nonspecific genetic predisposition in cooperation with psychological factors leads into the uprise and development of anxio-
us conditions.
In this kind of explanation the questions about the nature, noted genetic predisposition come out. In other, more simple, words, what
is inherited in the case of anxious conditions and panic disorder and if children of patients with panic disorder inherit the same disorder.
The majority of research scientists suggest that the cacoethes and hypersensitiveness for the uprise and development of anxious
conditions are inherited and they are based on enhanced autonomous nervous system reactivity or on the unstableness of neurotran-
smitter system that determines the global organism reactivity.
Meanwhile, the existence of cacoethes and hypersensitiveness for the anxious conditions uprise and development doesnt mean
sure disease development. Maybe the cacoethes is anchored in development basement of known personality of type A, by whom the
essential hypertension is developing. The essential hypertension could be followed by the existence of anxiety but it couldnt be as well.
It is also possible that the cacoethes just reduces threshold for specific senses and activities which, in cooperation with psycholo-
gical factors, lead into the disease onset. This kind of explanation can be only the peak of the enhanced reactivity basement to the
stress or can bean anxiety manifestation. It was proved by many researches that only features of personality, such as flap, tendency to
react anxiously, hypersensitiveness and shyness are inherited. It is proved that neuroticism as personality feature is inherited. Other
authors have found out that personality feature highly correlates in twins couples, no matter if they have grown up together or not.
The high correlation of personality features for anxiety in monozygote twins couples have been proved, meanwhile it hasnt been pro-
ved in dizygote twins couples.
A personality that has anxious features (anxious character) goes through unpleasant psychosocial factors or through stress with anxio-
us reactions. The way to the symptoms of panic attacks and panic disorder is very short when a long term and intensive fear comes out.
Finally, children of patients who are diagnosed with panic disorder do not straightaway inherit the same disorder. However, even
this fact cant be certainly confirmed.
50% of daughters and 10% of sons who suffer from panic disorder have symptoms which permit to make the right diagnosis.
In conclusion, we have to state that geneticists have not said the final word on the confirmation of basement for panic disorder
uprise and development.
Researches in the area of molecular biology are at the center of attention.
Preliminary results of 29 genetic markers of 26 families with positive history of panic disorder have been reported and they have
shown that there is a connection between panic disorder and patients chromosome status, especially in chromosome 16 and 22.
Implementation of this new technology into genetic research of patients with panic disorder and twin couples with certain disea-
se has allowed us to accept genetic basement of panic disorder uprise and development as comprehensive problem. The results that
should be found out are expected with great attention.
CONCLUSION
Thanks to patients who suffer from panic disorder and thanks to enthusiasm in psychiatry, positive family history of certain dis-
order, disease can be helpful for early diagnostic testing and for sufficient therapy.
Everything we are supposed to do is to get quality family history.
BIBLIOGRAPHY
Eri Lj., 1991: Priina stanja, II dopunjeno i proreno izdanje, Beograd- Zagreb, 1- 309: 56- 57, 67- 69
Hales R.E., Yudovsky S.C., Talbott J.A., 1994: Textbook of psychiatry, 2- nd Edition, The American Psychiatric Press, 1- 1608, 37- 71
Raboch J., Prako J., Seifertov D., 1999: Panick stavy 11 dl, vyd. SKB, 6- 56: 29

78
TREATMENT OF SOMATOFORM AND PSYCHOSOMATIC DISORDERS AT
OUTPATIENT PSYCHIATRIC CENTER

ABSTRACT
Somatoform disorders (SFD) refer to a subgroup of mental disorders where physical symptoms are not conditioned by
physical structural defect. (F45). Patients with somatoform disorders suffer a wide range of physical symptoms e.g. pain, nau-
sea, fatigue, vegetative symptoms and repeatedly insist on physical examinations although previous examinations were negati-
ve (Smolik, 1996). Asthma, dermatitis, eczema, peptic ulcers, mucous colitis and ulcerative colitis belong to a group of psycho-
somatic disorders classified in psychiatry as mental and behavioral factors attributed to other diseases (F54), (Smolik, 1996).
We studied cohort of 46 patients, 21 patients with diagnosis F45 (women N=14 total average age =49 years) and 25 pati-
ents with diagnosis F 54 (women N=-17 total average age=53 years). In both groups we observed comorbidity with other men-
tal disorders and made survey of applied theraphy. The most common line of theraphy in patients with somatoform disorders
was combination of atypical neurolepticum (sulpirid) + SSRI and anxiolytic agent (8 patients). On the other hand patients with
psychosomatic disorders were mostly treated with SSRI + anxiolytic agent (15 patients) or with combination of atypical neuro-
lepticum (sulpirid) + SSRI and anxiolytic agent (8 patients). Patients with somatoform disorders suffered especially from gastro-
intestinal tract disturbances i.e. neurosis, dyspepsia and psychogenic aerophagia (F.45.31) 10 patients, cardiovascular disorders
(F.45.30) 3 patients. 2 patients had unusual feelings of burning skin (F.45.38). Psychosomatic disorders most frequently occurring
were asthma, migraine and peptic ulcer disease. All patients suffered from the symptoms for the average of 2 or more years.
Key words: Somatoform disorders (F45), mental and behavioral factors attributed to other diseases- psychosomatic disor-
ders (F54), sulpirid.

INTRODUCTION
Patients with somatoform and psychosomatic disorders are the most frequent subjects visiting general practitioners. They
can experience hypertension, asthma, diverse eczemas, gastrointestinal and urogenital problems. Moreover, physical symptoms
can sometimes mask depressive symptoms (formerly known as larval or masked depression, today somatoform disorder) or the
physical symptoms occur during depressive episode (somatic syndrome previously referred to as biological, vital, melancholic
or endogenomorphous) (Smolik, 1996).
Making the diagnosis we should not forget to omit mood disorders in somatic diseases malign tumors, drug-induced depre-
ssion, infection, etc.). They are very important in differencial diagnosis. Psychosomatic disorders together with psychosomatic
medicine form interdisciplinary field that comprises collaboration of general practitioners, internists, cardiologists, gastroente-
rologists, surgeons, neurologists and psychiatrists. Sulpirid 2- methoxy benzamid in not only used in the treatment of psycho-
tic and depressive disorders but also in somatoform and psychosomatic disorders. The mechanism of action of sulpirid in afo-
rementioned disorders is not explicitly known. Although dopamine agonists (DA) have antidepressive effect, there are certain
neuroleptics (DA receptor antagonists) that show antidepressive action, also (Schatzberg, Nemeroff, 2001, Janicak 2001). One
of the possible explanations of this paradoxical effect (potency of sulpirid in therapy of depressive and somatoform disorders)
is that neuroleptics, in small doses, can have antidepressive effect acting as DA autoreceptor antagonists thus increasing DA
turnover (Floyd, 1995). Selective blockade of limbic DA receptors with sulpirid is associated with low incidence of neurologic
adverse events. Sulpirid can antagonise DA receptors in blood vessels and gastrointestinal smooth muscles, as well (Turjanski,
1996). Using high doses of sulpirid (400-600mg per day) antipsychotic effect becomes dominant (Janicak, 2001). However,
with low doses of sulpirid (150-300mg per day) we manage psychosomatic, neurotic and depressive disorders (Turjanski, 1996).
Rimon states that sulpirid is efficacious in the treatment of various psychiatric disturbances. Given dose of 100-150mg per day
is applicated in neurotic and depressive disorders. Gastrointestinal symptoms are the most common symptoms in subjects with
somatoform disorders (Fraxinos, 1995). Therefore sulpirid represents new therapeutical modality in the management of those
disorders where visceral hypersensitivity and somatoform component play crucial role (Fraxinos, 1996). Likewise sulpirid co-
mes with new alternative for the treatment of psychosomatic disorders since psychoemotional background is very significant
in the etiopathogenesis of above-mentioned disorders (Lemoine, 1996).
Sulpirid does not decrease the amount of gastric acid in stomach, reduces postprandial serum gastrin levels, stimulates
muconasal defence factors and basal or histamine-stimulated acid production stays unchanged during the course of long-term
theraphy (Lemoine, 1996).
Furthermore sulpirid is potent in controlling stress due to its well studied CNS effects (Crismer, 1972).

METHODS
We studied cohort of 46 patients, 21 patients with main diagnosis of somatoform disorder and 25 patients with diagnosis of
psychosomatic disorder. To interpret comorbidity with other psychiatric diseases and to determine applicated therapy we re-
trospectively analysed patients files without using structural scale.
Enrollment criteria:
ICD- 10 criteria for somatoform and psychosomatic disorder.
Age 18 to 80 years.
Treated more then 2 years in an outpatient psychiatric center.

79
OBJECTIVES:
To find the most common somatoform and psychosomatic disorders at our outpatient center
To map incidence of comorbitity with other psychical disturbances.
To carry out a survey of the most frequently applied therapeuticals in somatoform and psychosomatic disorders at our out-
patient clinic.

RESULTS
We enrolled a cohort of 46 patients, 21 patients with main diagnosis F45 and 25 patients with diagnosis F54. Average age is
given in Table 1 and Table lb. The most frequent somatoform and psychosomatic disorders were gastrointestinal disturbances
(Tab.2) The comorbidity of somatoform disorders with other mental disorders appeared in the sample of 9 patients, 12 patients
did not show evidence of comorbidity (Tab. 2). The most common psychosomatic disorders were asthma, migraine and pep-
tic ulcer disease. 19 patients had comorbidity with other mental disorders, 6 patients were without comorbidity (Tab. 3). The
most preferred therapy for somatoform disorders was a combination of atypical neurolepticum (sulpirid) + SSRI + anxiolytic
agent (Tab. 4). An overview of SSRI used for this diagnosis is presented in Table 5. Psychosomatic disorders were treated with
SSRI + anxiolytic agent (despite of high comorbidity with anxiety and depressive disorders) or with atypical neurolepticum +
SSRI + anxiolytic agent (Tab 4b).

DISCUSSION
Somatoforrn disorders present heavy therapeutical problem, not only for general practitioners but also for specialised cli-
nicians during patients hospital stay , because patients symptoms vary widely (Lemoine, 1996). Described disorders cover a
vast amount of psychiatric and other conslutation services (Ignjati). Despite of many repeated examinations, the explanation
that the disorder is not conditioned by structural defect, seems to be unsatisfactory and patients are finally placed in psycha-
tric outpatient centers. Correct diagnosis and treatment prevents ongoing symptoms of chronic illness. Depressive symptoms
may be evident and attributed to somatic or functional symptoms. On the other hand psychatric symptoms can be sometimes
masked by somatic or functional symptoms (Lemoine, 1996). Low doses of sulpirid (100-200mg per day) may be effective in
the treatment of various somatoform disorders. In one double blinded study, Nishida et al. (1974) compared efficiency of sul-
pirid (150-200mg per day) to oxazolam (30-60mg per day) in subjects with somatoform disorders.
At the end of 3-week period patients on sulpirid showed significant improvement compared to oxazolam. Chent and Sttenhouver
(1972) followed 30 patients with symptoms of tachycardia and dyspnoea. Results indicated reduction of symptoms while trea-
ted with low doses of sulpirid. Psychosomatic medicine is an interdisciplinary branch of medicine with typical psychosomatic
disorders e.g. asthma, peptic ulcer disease, migraine and ulcerative colitis (Smolik, 1994). Because of participation of psycho-
emotional component in the etiopathogenesis, sulpirid has a significant role in modification and therapy of psychosomatic dis-
orders (Lemoine, 1996). Migraine is also a very common symptom. Many authors tried to use sulpirid to reduce frequency of
headaches and migraine (Aschoff, 1997, Barr, 1970).
Hakkarainen and Vukari (1973) observed 30 subjects with migraine and 30 subjects with tension headaches, in both groups
symptoms were associated with psychosomatic symptoms. Daily dose of sulpirid was 150mg. Compared to placebo the results
in sulpirid group were much better and lead to alleviation of migraine and tension headaches (Lemoine, 1996).
Application of sulpirid in 20 patients with asthma reduced the rate of attacks. According to Chevalier (1985), although sulpi-
rid has no direct impact on pathophysiology of asthma, it is effective in the blockade of vicious circle of psychosomatic factors
that contribute to pathophysiology of asthma. Several studies examined potential role of sulpirid (150-200mg per day) in sexu-
al and urological disturbances (Mazeman,1975). The cons of studies that examined the efficiency of sulpirid in a variety of so-
matoform and psychosomatic disorders are: short period of examination, there are not double blinded, not placebo controlled
and they focused on small number of patients. In spite of this fact, various studies support the application of sulpirid in soma-
toform and psychosomatic disorders treatment. Our survey did not evaluate efficiency of therapy for F45 and F54, but demon-
strates the maximum possible use of combined therapy with atypical neurolepticum (sulpirid) + SSRI + anxiolytic agent is for
discussed disorders. Average dose of sulpirid in our cohort was 100-150mg per day which is comparable to studies mentioned
above. Given results suggest that therapeutical efficiency of sulpirid is indicated by its significant impact upon psycho-emoti-
onal component what might be common for miscellaneous somatoform disorders (Lemoine, 1996). Irritable bowel syndrome
is another severe illness with prevalence of 15-30% in our population. It is characterised by abdominal pain, abdominal discom-
fort (symptoms for at least 3 months and several days in a week) and altered bowel habits. There are three major pathophysio-
logical factors for irritable bowel disease: abnormal motility, sensitivity and a type of personality (Almy and Tulin, 1947). Those
patients suffer from anxiety, depression and neurotic comorbidity with anxiety and depressive disorders) or with atypical ne-
urolepticum + SSRI + anxiolytic agent (Tab 4b).

DISCUSSION
Somatoforrn disorders present heavy therapeutical problem, not only for general practitioners but also for specialised cli-
nicians during patients hospital stay , because patients symptoms vary widely (Lemoine, 1996). Described disorders cover a
vast amount of psychiatric and other conslutation services (Ignjati). Despite of many repeated examinations, the explanation
that the disorder is not conditioned by structural defect, seems to be unsatisfactory and patients are finally placed in psycha-
tric outpatient centers. Correct diagnosis and treatment prevents ongoing symptoms of chronic illness. Depressive symptoms

80
may be evident and attributed to somatic or functional symptoms. On the other hand psychatric symptoms can be sometimes
masked by somatic or functional symptoms (Lemoine, 1996). Low doses of sulpirid (100-200mg per day) may be effective in
the treatment of various somatoform disorders. In one double blinded study, Nishida et al. (1974) compared efficiency of sul-
pirid (150-200mg per day) to oxazolam (30-60mg per day) in subjects with somatoform disorders.
At the end of 3-week period patients on sulpirid showed significant improvement compared to oxazolam. Chent and Sttenhouver
(1972) followed 30 patients with symptoms of tachycardia and dyspnoea. Results indicated reduction of symptoms while trea-
ted with low doses of sulpirid. Psychosomatic medicine is an interdisciplinary branch of medicine with typical psychosomatic
disorders e.g. asthma, peptic ulcer disease, migraine and ulcerative colitis (Smolik, 1994). Because of participation of psycho-
emotional component in the etiopathogenesis, sulpirid has a significant role in modification and therapy of psychosomatic dis-
orders (Lemoine, 1996). Migraine is also a very common symptom. Many authors tried to use sulpirid to reduce frequency of
headaches and migraine (Aschoff, 1997, Barr, 1970).
Hakkarainen and Vukari (1973) observed 30 subjects with migraine and 30 subjects with tension headaches, in both groups
symptoms were associated with psychosomatic symptoms. Daily dose of sulpirid was 150mg. Compared to placebo the results
in sulpirid group were much better and lead to alleviation of migraine and tension headaches (Lemoine, 1996).
Application of sulpirid in 20 patients with asthma reduced the rate of attacks. According to Chevalier (1985), although sulpi-
rid has no direct impact on pathophysiology of asthma, it is effective in the blockade of vicious circle of psychosomatic factors
that contribute to pathophysiology of asthma. Several studies examined potential role of sulpirid (150-200mg per day) in sexu-
al and urological disturbances (Mazeman,1975). The cons of studies that examined the efficiency of sulpirid in a variety of so-
matoform and psychosomatic disorders are: short period of examination, there are not double blinded, not placebo controlled
and they focused on small number of patients. In spite of this fact, various studies support the application of sulpirid in soma-
toform and psychosomatic disorders treatment. Our survey did not evaluate efficiency of therapy for F45 and F54, but demon-
strates the maximum possible use of combined therapy with atypical neurolepticum (sulpirid) + SSRI + anxiolytic agent is for
discussed disorders. Average dose of sulpirid in our cohort was 100-150mg per day which is comparable to studies mentioned
above. Given results suggest that therapeutical efficiency of sulpirid is indicated by its significant impact upon psycho-emoti-
onal component what might be common for miscellaneous somatoform disorders (Lemoine, 1996). Irritable bowel syndrome
is another severe illness with prevalence of 15-30% in our population. It is characterised by abdominal pain, abdominal discom-
fort (symptoms for at least 3 months and several days in a week) and altered bowel habits. There are three major pathophysio-
logical factors for irritable bowel disease: abnormal motility, sensitivity and a type of personality (Almy and Tulin, 1947). Those
patients suffer from anxiety, depression and neurotic disturbances (Fraxinos) that corresponds with our data (high comorbi-
dity with anxiety and depression). While the efficiency of sulpirid in the treatment of irritable bowel disease is under theoreti-
cal investigation, sulpirid may directly modify physiological processes of patients with peptic ulcer disease. Additional sulpirids
quality is the capability to diminish stress factors. Sulpirid has dual function in reducing stress-induced ulcerations. The local
activity normalizes vascularization during pre-ulcerative and ulcerative period and it also indirectly modifies gastric secretion
and psychological activity that contribute to formation of gastric ulcerations (Stein et al., 1994).

CONCLUSION
Somatoforrn and psychosomatic disorders are very frequent in psychatric outpatient care centers. In differential diagno-
sis it is quite important to exclude depressive episodes since many patients suffering from depression do not present with any
signs of depression. The term somatization applies to somatic symptoms that express emotional discomfort and may lead
to misdiagnosis. A number of depressive subjects with somatic component really have somatic disease, but treatment is often
insufficient. On the other hand many patients with inexplicable diffuse symptoms come to psychiatrist and are diagnosed with
anxiety or depressive disorder (Stahl,). Correct diagnosis of somatoform and psychosomatic disorder can help with the choice
of pharmacological intervention relevently combined with psychotherapy. One such possibility is represented by combination
of sulpirid + SSRI + anxiolytic agent. However this modality needs further clinical studies.
LITERATURE
Table 1 a
Diagnose Number of patients Age
F.45
Male
Female
Total

Table 1 b
Diagnose Number of patients Age
F.54
Male
Female
Total
Table 2
Diagnose Number of patients
F.45 somatoform disorder

81
 F.45.2 hypochondric disorder
F.45.30 cardio and KVS system
F.45.31 superior GIT
F.45.32 inferior GIT
F.45.33 respiratory system
F.45,34 urogenital system
F.45.38 other apparatus or system
F.45.4 chronical somatoform painful disorder
Total
Table 3 a
DO Without cormobidity
Table 3 b
DG Without cormobidity
Table 4 a
DG
SSRI
TCA
anxiolytic agent
SSRI + anxiolytic agent
SSRI + typical neurolepticum
Atypical neurolepticum
Biston
Atypical neurolepticum / sulpirid / + SSRI + anxiolytic agent
Total
Table 4 b
DO
SSRI
SSRI + anxiolytic agent
Atypical neurolepticum / sulpirid / + SSRI + anxiolytic agent
Other
Total

CASUISTIC
A 24-years old patient was examined at our outpatient psychiatric center in February 2003 for the first time. He had the
first contact with psychiatric center / paediapsychiatric / at the age of 13 only psychotherapy ,without psychopharrnacotherapy.
At the age of 21 he was treated at outpatient psychiatric center with a diagnose of somatoform disorder, gastric neurosis
F.45.31 with the following advised therapy: maprotilinum 150mg pro die, advised deep psychotherapy, maprotilinum gradually
ex, a change for fluvoxamine.
The patient travelled abroad for 2 months - without difficulties, he has commited the therapy.
RA:
He had been brouht up by his parents until he was 13. Then his father died under unknown circumstances, his family refused
the suspicion of suicide, he has an older sister, ocassional depressive episodes, t.b.: 0, DM: grandfather, ICHS: grandfather, IM:
grandfather, NCMP: probably the great grandparents, ca: great grand father had bowels cancer, alcohol : 0, neuropsychiatric
stress: grand mother was treated at psychiatric center, but he can not name her diagnose, his mother is under monitoring by
outpatient neurology center, because of sclerosis multiplex.
OA:
He cameover usual children diseases, more serious diseases in childhood: at the age of 6 months - coeliakia, operations:
APE, TE, injuries: 0, fractures: 0, unconsciousness : 0, concussion of the brain: caused by downfall, there was only RTG done,
allergy to medicine or to food not declared.
SA:
The patient has graduated on secondary industrial school, at this time unemployed, character: rather self-contained, intro-
vert, pesimistic, with schizoid features, he does not go out very often, MS rejected, without seriuos relationship, only tempo-
rary occasional relationships.
TO:
He has been suffering from gastric neurosis from the time of his studies on secondary school, It was bearable till the age of
16, it has been getting worse since 2000.
When he was abroad, he had no problems. Last year when he came back, his condition started to get worse, it is critical aga-
in, he tends to vomit, he is loosing his weight, aversion to food, he feels sick all the time, he has sleeeping problems, he thinks
he is not able to go to meet people, only because he feels sick, not because of his anxiety about meeting people.
Psychiatric objective:

82
 The patient comes to the psychiatric center alone, neat, he accepts social formalities, hygiene kept, mimicry and gesticula-
tion appropriate, psychomotoric tempo is appropriate.
Consciousness is clear, orientation by person, place, time, situation is right, mood subdepressive, without suicide tenden-
cies, affectivity oscillates, his thoughts are strongly orientated to his somatic qualitative problems of his gatrointestinal tract,
without false contents, perception without qualitative disorders, attention good, IMF appropriate to the age, education, surro-
undings, personality rather introvert, behaviour appropriate.
DG: F.45
F.43.31
Advise:
Paroxetin 20 mg pro die
Clonazepam 2 mg pro die
Sulprid 100 mg pro die
ETIOPATHOGENIC VIEW:
Psychologically the patients self-confidence is lower, psychosocially his gatric problems could indicate the need of fathers love.
Psychoanalytically somatic disorder is an expression of patients anger against unknown person who is responsibile for the
pain caused by fathers death.
Behaviouraly, somatic disorder would express an imitation of his mothers disease (sclerosis multiplex, depressive episodes
) and strict upbringing by one of his parents (mother).

BEGINNING AND DEVELOPMENT OF DISEASE

The first symptoms of somatoform disorder occured at the age of 13, in the period of adolenscence, it means before the age
of 30, it was in close relation with violent death of his father, which meant heavy stress for the young man,
Due to the considerable somatic disorder, the patient was repeatedly examined although with negative diagnose. After 5 ye-
ars of lasting physical problems without scructual defect, the patient was advised to see a mental specialist.
His dignose was somatoform disorder (gastric neurosis) with advised therapy.
The patient was working abroad for 2 months, where he did not have any physical difficulties. After his return, his condition
got worse: nauzei, vomiting, aversion to food, loosing weight, wind....
In differencial diagnoses, we have tried to eliminate these somatic diseases (collagenoses, S M.,myastenia gravis, AIDS, hyper-
tyreosis, chronical infection diseases ...), whose physical symptoms can also be temporary and changeable.
We eliminated heavy depressive disorder with somatic symptoms, as there are depressive episodes in the patients family
anamnesis ( mother, sister ).
We eliminated schizophrenia and other psychotic diseases.
Concerning the comorbidity we considered stress and endurance situations.
TH:
Besides psychopharmacotherapy we have advised the patient for psychotherapy as well ( cognito-behavioral psychotherapy )

1.CHECK UP
After a month of treatment , the patient felt better, physical symptoms decreased, at this time the patient is looking for the
job in Slovakia.

83
COGNITIVE AND BEHAVIORAL PSYCHOTHERAPY OF SPECIFIC PHOBIA-
CASUISTIC

AUTHORS
Dana Ignjatovic 1.
Milan Ignjatovic 1,
Silvia Beatriz Schweitzer 2
1,2-Non governmental psychiatric health clinic,Cesta k nemocnici 1,Slovakia
3-Hopital Durand, Buenos Aires, Argentina

ABSTRACT
Cognitive and behavioral psychotherapy-Beck, 1967, Ellis, 1962- is a integrion of cognitive and behavioral direstions. Cognitive
and behavioral psychotherapy is operational and very empirical, what is very important in the efficacy of psychotherapeutical
treatment. I would like to introduce you my patient-24 year young woman.
She finished catholic secondary school and private business academy with certificate. She work in a shop, like shop-assistant
and she lives with her family /mother, father, younger sister and brother lives alone/.
She cames to psychiatrist with many problems. She feels very anxious, perfectionistic, she likes when everything is O.K., she
likes to be alone in her room, she contol everything 7 times or more. She cant travel alone in the bus, or train, she has a diar-
hoea, tachycardia, tachypnoe, she feels very bad, she doesnt go to bih shops, big squares, she thinks that everybody are loo-
king for her and she has a phobia from blood and injections, all the time she fall off, she feels, when it comes to her, and she
prepares a bottle of water for her.
It was really too many problems for the first time... So we made cognitive assesment and we formulated together 8 means
problems, and goals of psychotherapy. We start with psychopharmacotherapy, because of a long time of psychical problems.

DIAGNOSIS:
F.40.01 agoraphobia with panic disorder
F.42 or diferential diagnostics: F.60 with obsedant- compulsive
F.40.2 specific phobia
Therapy: paroxetin/20mg/ 1-0-0
Clonazepamum/0,5mg/ 1/2-0-1/2

ACCTUALLY PROBLEMS AND SYMPTOMS:

She is working in a shop, she has agoraphobia and phobi from squares, big rooms, she cant travel by bus or by train alone,
she had a diarhoea, she control 7 or more times if the doors are closed, she feels very anxious, panic, after getting or seeing
injections, she cant stay in a shop for a long time.

INTERPERSONAL CONNECTIONS:
Good connections with her mother, but she did so much for family, she have to do much for herself.
Father is dominant, expansive, he never said to her and her mother she is clever and successfull. She doesnt have many fri-
ends, only one, she has problems with communications during basic shool.

BEHAVIOUR DURING THE FIRST DIALOGUE:

24 year young woman, with striking makeup, but with inconspisious behaviour, answer the adequate, not so spontaneous.
Intelect is higher. Somatic status and laboratory tests/internal,EEG,laboratory scrrening/ are physiological.
Actually problem 1.agoraphobia with panic disorder
2.specific phobia
3.personality disorders with obsedant and compulsive
symptomatology
Personality Senzitive
Pedant
Anxious
Obsedant and compulsive
Cognitive schemata Im not so good for my father
When I start to speak everybody thinks I am not clever...
Behavioral actual Ampatia
Submission
Rationalisation of avoidant behavior
We start psychotherapy cognitive and behavioral psychotherapy during the pharmacotherapy, which tries 1 and a half years.

84
 It was successfull in combination psychopharmacotherapy and psychotherapy and during this time the patients is without
symptoms she has on the begining and without psychopharmacotherapy, and she feels very well.

CONCLUSION
The psychotherapy is very important par of the complete therapy of the patients, because the patient is a bio-psycho-social
complex/Eri, 1999/., and the most important is combination of psychotherapy and psychopharmacotherapy in the treatment.
The treatment of this patient was very complex, and complicated, because of many problems.
But the compliance between patients and psychotherapeutist was very good what is important for the next treatment, But
it may be some times problematic for the finishing the treatment, when the goals are not clear and strong enough.
But from our experiences combination of psychopharmacotherapy and psychotherapy is the most effective in the treatment
of agoraphobia with panic disorder/Igjatovic M.,Ignjatovic D.,Luhaovice, poster presentation, 2003/.

THANK YOU FOR YOUR ATTENTION!

Presented on EABCT,XXXIII.Annual
Congress of the EABECT,Prague, 2003

85
PHARMACOECONOMICS OF THE TREATMENT OF AGORAPHOBIA WITH
PANIC DISORDER
AUTHORS
Milan Ignjatovi 1
Dana Ignjatoviov 2
Hosk Ladislav 3

1-Psychiatric out Department of Polichnic,Bansk Bystrica, Slovak republic

2-Psychiatric out Department of Policlinic,Bansk Bystrica, Slovak republic
3-Medical Faculty,Psychiatric Clinic Hradec Krlov Czech republic
PURPOSE OF THE STUDY
The main objective of our study was to determine the average daily and total phannacotherapy costs of agoraphobia with panic disorder when
treated by non- psychiatrist outpatient practitioners, compared with accurate diagnostics and treatment in psychiatric outpatient department.
Average daily and total number of tablets, taken by patients during the examined period, was also analyzed.
SAMPLE GROUP AND METHOD
in the card files of the psychiatric outpatient department of this studys first author
all patients suffering from agoraphobia with panic disorder for longer than two years, were selected
who were previously treatedby other therapists than psychiatrists
agoraphobia was diagnosed according to DSM-IV clasiffication
patients with psychiatric comorbidity, together preganant women were excluded from the research
study was not submitted for the approval of the ethics comission, as it was a retrospective axamination of medical records, without the par-
ticipation of patients, or any influence on their treatment
SUMMARY OF RESULTS AND STATISTICAL ASSESMENTS
for statistical processing og acquired data,NCSS 2000 computer software was used
distribution normality of aquired values,relating to individual variables,was evaluated using Shapiro-calks and Kolmogorov-Smirnov tests
the distribution was abnormal, statistical significance of differences, relating to measured valeus, was examined by Wilcoxon nonparametric test
RESULTS
Results are stated in the table 1.
Although the average daily price of pharmacotherapy was higher in the case of psychiatric treatment of the psychic disorder, average total
medication costs were lower, compared with treatment carried out by practiocioners-nonpsychiatrists.
Significantly lower were also average numbers of tablets prescribed by psychiatrists, opposite to previous medical treatment whether their
daily or total amount was examined.
All described differencie are statistically highly significant.
CONCLUSION
Results of this study prove the lack of economy and ineffectiveness of agoraphobia with panic disorder treatment in outpatient departments
of non-psychiatric specialists in Slovak republic.
Proper diagnostics and psychiatric treatment results not only in improvements of clinical state of patients, but also in savings of total direct
treatment costs of pharmacotherapy.
Consodering historically recent division of the common state of Czech and Slovaks, authors presume, that acquired results can be applied
also for the Czech republic.

TABLE 1
The phartmacotherapy costs and the number of the tablets.they had been taken in the outpatient nonpsychiatrists department and com-
paration with psychiatric outpatient care
Patients suffering from agoraphobia with panic disorder
Treatment by nonpsy-*chiatrists Treatment by psychiatrists Wilcoxon nonpara-metric
outpatients practio-cioners Medin test /p/
Medin /Min.-Max./ /Min.-Max./
Daily price of 62,9 82,0 0,0493
medication /Sk/ /1,0-230,9/ /40,0-333,1/

Total price of 123 372,0 10 666,5 0,0000

pharma-cotherapy /5400,0-1246 860,0/ /82,0-37824,0/
Avarage daily number of tablets 7,0 2,0 0,0000
/1,0-20,0/ /1,0-7,0/
Total number of 14 400,0 730,0 0,0000
tablets /1 170,0-75 600,0/ /365,0-2 555,0/

86
PHARMACOLOGICAL TREATMENT OF LATE-LIFE DEPRESSION

AUTHORS
DANA IGNJATOVIC 1 a
MILAN IGNJATOVIC 1 b
DAVID J. NUTT 2
1 a- Mentee of CINP Mentor-Mentee Program, Non Governmental Psychiatric out Department, Jaseov 1,97401 Bansk
Bystrica, Slovak republic
1 b- Coauthor, Non Governmental Psychiatric out Department, Jaseov 1,97401 Bansk Bystrica, Slovak republic
2- Mentor of CINP Mentor - Mentee Program, Professor of Psychopharmacology ,Head of Department of Community Based
Medicine, University of Bristol, Psychopharmacology Unit, Bristol

ABSTRACT
Late-life depression is common serious health problem with high pharmacotherapy response rate (Solai 2000).
Prevalence of depression is 12-15% (Gottfries 1996, Gottfries 1992), but some authors (Mayon and Hawton 1986, Katona
1994) report higher depression prevalence (11-59%) in elderly patients (Katona 1997).
Late-life depression is frequently manifested in atypical form with somatic symptoms (Goftfries 1996, Kurzthaler 2001).
Approximately 60% of depressive patients in elderly suffer from somatic disease and beside the antidepressants they are
treated with other medication (Gottfries 1996).
Pharmaceuticals such as antihypertensive drugs /metyldopa, propranolol/, antiparkinsonics /levodopa, karbidopa, amanta-
dine/, hormones /estrogen, progesteron/, corticoids, antituberculotics and anticancer drugs /vincristine, vinblastinel are very
frequently used in elderly and could provoke depressive disorder (Hales 1991, Gottfries 1996, Karlsson 1996, Cooke 2001).
Misdiagnosed and untreated late-life depression is very common (Gottfries 1999). Depression can be unrecognized due to
other medication, alcohol or cognitive dysfunction (Gottfries 1999).
Problems with diagnostics of depression and vague pharmacological guidelines could reduce number of treated patients
and efficiency of antidepressive treatment in depressive patients with dementia (Alexopoulos 1996).
Very important tool is assessment of severity of depression according depression rating scales: GDS scale /Geriatric Depression
Scale, /Zung Self Rating Scale /SDS/, The Dementia Mood Assessment Scale and The Cornell Scale for Depression in Dementia
or Hamilton scale /HAMD/ (Alexopoulos 1996).
SSRIs (Selective Serotonine Reuptake Inhibitors) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline represent
new group of antidepressants developed in 1980 accepted for treatment of late-life depression (Kurzthaler 2001, Briley 1998).
Citalopram is one of the most frequently used SSRIs in the treatment of late-life depression (Jirk 2002).
Our study was designed as retrospective assessment of 58 elderly patients in the treatment of depression. Patients fulfilled
inclusion criteria for depression with or without dementia. 42 patients were treated with citalopram 20mg daily, 7patients were
treated with sertraline 50mg daily and 3 patients with paroxetine 20mg daily, 4 patients used fluvoxamin 50 mg pro die, 1 pati-
ent used fluoxetin 20mg pro die,1 patient used trazodon 75mg pro die, 1 patient used maprotilin 75mg pro die and 1 venlafaxin
50mg pro die.
Incidence of adverse events during antidepressive therapy was monitored.
Citalopram was the most frequently used and best-tolerated antidepressant.
28 patients were treated with anxiolytics-21 used clonazepam 0.5 mg daily for sleeping disorders. Neuroleptics were used in
18 patients with behavioral and psychological symptoms of dementia (BPSD).
Each of 58 patients suffered from at least one co-morbid chronic somatic disease.

INTRODUCTION
Depression in age over 65 is common (Ragneskog 1998) and became an important medical and social problem.
Undiagnosed and untreated depression can lead to suicide (Waern 1996).
Elderly patients are treated for various somatic chronic diseases. Another very frequent health problem in elderly is chronic
pain. Therapy of somatic diseases itself can lead to depression. Around 63% of Americans over 50 years are treated with drugs
for more than one chronic disease (Salzman 1997).
Antidepressants were used for the first time for the treatment of chronic pain 40 years ago (Opavsk 2002).
The results of the treatment are ambivalent. SSRIs seem not to have direct analgetic effect, but they potentiate the effect
of analgeties (Opavsk 2002).
According Stephen C. Cook depression use to be co-morbid to syndrome of chronic pain in cancer or rheumatoid arthritis.
More than 50% of patients with chronic pain suffer from depression. Adequate antidepressive therapy reduces chronic pain
(Cooke 2001).
Atypical symptoms of depression in elderly, presence of somatic disease and cognitive deterioration lead to diagnostic pro-
blems (Lovestone 2001). Cognitive impairment can cause problems in evaluation of anamnesis, mainly in patients staying in
Elderly homes and Homes of social care.
Moreover non-cognitive /psychological /symptoms of dementia can include depressive symptoms (Karlsson 1996).

87
 Some authors recognized late-life depression with or without dementia as specific disorder with different etiology, symp-
toms and treatment strategy (Karlsson 1996).
Other studies suggest, that sometime depression occurs before cognitive impairment in patients with dementia (Reding 1985).
In study of 123 depressive patients Hans Ragneskog found 76% of patients with dementia (Ragneskog 1996).
Depression simulating dementia can occur in 4-7% of patients (Koukolk 1999).
Incidence of depression among patients with DAT (Alzheimer dementia) is 25-33%. Patients with DAT have significantly lower
concentrations of serotonine (5-hydroxytryptamine, 5-HT) in brain (Ragneskog 1996).
Decreased concentration of 5-HT and 5-HIAA was found also in patients with VAD (vascular dementia) (Gottfries 1990,
Baldin 1987).
Pathophysiology of depression in elderly indicates possible association of cognitive impairment with depressive symptoms
which both could be symptoms of one degenerative brain disease (Karlsson 1996).
Uncertainties in diagnostic, comorbidity of depression allow us to consider broader spectrum of clinical decisions in dia-
gnostic process and at the same time they did it more difficult.Tricyclic antidepressants (TCAs) are not recommended for tre-
atment of late-life depression. TCAs similarly to some neuroleptics have also strong anticholinergic effect. They can cause ort-
hostatic hypotension, confusion and rapid deterioration of cognitive functions (Lovestone 2000, Kurzthaler 2001, vestka 1995).
In contrast to TCAs, SSRIs are drugs of first choice for treatment of late-life depression.
Adverse events can include gastrointestinal symptoms such as nausea and vomitus especially during first weeks of treatment
(Cooke 2001).
Fluoxetine can cause agitation, anxiety, and/or insomnia in elderly patients (Cooke 2001).
Fluoxetine, fluvoxamine and paroxetine have significantly more drug-drug interactions in comparison with citalopram a ser-
traline (Solai 2001).
Several studies approved positive effect of citalopram in treatment of depression and other emotional disturbances in elderly
patients with low frequency of side effects (Ragneskog 1996). Citalopram is one of the most frequently used drug in geriatric
patients (Jirk 2002). Efficacy of citalopram is comparable to that of imipramine. Citalopram has antidepressive and anxiolytic
effect and is well tolerated in long-term treatment of elderly patients (Joubert 2000).
New perspective in treatment of late-life depression are antidepressive drugs such as bupropione, trazodone, nefazodone,
venlafaxine and mirtazapine (Cooke 2001).

METHODS
Total number of 58 patients, at least 65 years old with diagnosis of clinical depression with or without dementia were inclu-
ded in study. Examination of patients by initial GDS score and 17 items Hamilton scale for evaluation of depression (H. 1D) was
used in study.
Patients with somatic diseases were not excluded from the study. All patients have at least one of chronic somatic diseases
such as ischemic heart disease, II and III stage of hypertension according WHO criteria, polytopic chronic vertebrogenic algic
syndrome, chronic headache, chronic gastritis, ulcus ventriculi, chronic bronchitis, diabetes mellitus, hyperlipoproteinemia,
status post myocardial infarction and stroke. Patients with diagnosis of schizophrenia and schizoafective disorders, epilepsy,
alcoholism and another drug dependence were excluded from the study.

PATIENTS AND STUDY DESIGN

Study was designed as retrospective assessment of pharmacotherapy of depression during one month period at two priva-
te psychiatric outpatient units at Slovakia.
58 elderly patients were in the treatment of depression. Patients fulfilled inclusion criteria for depression with or without
dementia. 42 patients were treated with citalopram 20mg daily, 7patients were treated with sertraline 50mg daily and 3 pati-
ents with paroxetine 20mg daily, 4 patients used fluvoxamin 50 mg pro die, 1 patient used fluoxetin 20mg pro die,1 patient used
trazodon 75mg pro die, 1 patient used maprotilin 75mg pro die and 1 venlafaxin 50mg pro die.

CLINICAL INVESTIGATION
Diagnosis of depression was based on anamnesis, GDS /Geriatric Depression Scale/, HAMD /Hamilton Scale for Depression/,
CGI /Clinical Global Impression/. Rating scales were used only for baseline assessment in this study. Evaluation of treatment
efficacy was not the aim of our study.

THE AIM OF THE STUDY

Overview of antidepressive therapy in elderly during one month period at two private psychiatric out-patient units.
Overview of other psychopharmacotherapy and the undesirable effects of antidepressants.

RESULTS
58 elderly patients who fulfilled the inclusion criteria were included in study. The aim of study was to show overview of used
pharmacotherapy. Basic characteristics of study population were: men n=13, mean age 71,5 years /range 65-91/, women n=45 pa-
tients, mean age 76,4 years /range 65-93/.
We follow the psychopharmacotherapy of 58 depressive patients with or without dementia/Tab. 1./.

88
 The most frequent and the best tolerated antidepressant in elderly was citalopram/Tab. 2/.
19 patients used neuroleptics for stabilization behavioral and psychological symptoms of Dementia/tab. 3/
Anxiolytics used 28 patients/tab. 4/.
Overview of inhibitors ACHE and nootropics shows table 5.

DISCUSSION
Psychopharmacotherapy of late-life depression is challenging problem for physician in management of medication, and asse-
ssment of age-modified possible adverse events of drugs. Modification is related to pharrnacodynamics and pharmacokinetics
of drugs as well as drug-drug interactions with treatment of somatic diseases (Baumann 1998, vestka 1995).
SSRls- citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline are important in treatment of late-life depression
(Baumann 1998). The dose has to be adapted to liver and renal injury and other somatic diseases (Guttierez 2000).
Several studies approved initial half dose of SSRI during one week, for example 10mg citalopram daily and later 20mg citalo-
pram daily (Kasckow 2001), 20-30mg citalopram daily (Balldin 1987) up to 20-40mg citalopram daily (Guttierez 2000, Ragneskog
1996, Andersen 1994, Kyle 1998, Pollock 2000, Klysner 2000).
Efficacy of 20-40mg citalopram daily was compared to placebo (Pollock 2000), and TCA- 50-100mg amitriptyline daily (Kyle
1998, 2000). Efficacy of citalopram was similar to amitriptyline with lower frequency of drug adverse events.
In process of selection of antidepressive drug in geriatric patients is necessary to remember general guidelines for treatment
with antidepressive drugs. One should consider adverse events, log term safety and safety in overdose, efficacy in treatment of
previous episodes, present somatic diseases and concomitant medication (Jirk 2002, Hoschl 2002).
In geriatric patients SSRI antidepressants are drugs of first choice because of minimal adverse events (no cardiotoxic effect)
and good tolerability (vestka 1996).The most frequently used antidepressant is citalopram at daily dose of 20-40mg and ser-
traline (50-150mg daily). Fluoxetine can be also used for treatment of late-life depression, but long half-life and drug-drug inte-
ractions via cytochrome system need to be considered. Paroxetine has mild anticholinergic effect (Jirk 2002).
In our study, citalopram was used in initial dose of 10mg daily for one week, average dose 20 mg daily, maximal dose 40mg
daily. Sertraline was given in initial dose 25mg daily, average dose 75mg daily, paroxetine in average dose 20mg daily, fluoxetine
in average dose 20mg daily and fluvoxamine in initial dose of 50mg daily.
Mackle et al. evaluated efficacy and safety of citalopram in 98 elderly dement patient with noncognitive symptoms (56 - 94
years old) in double blind placebo controlled multiphasic study. Citalopram was found to have excellent safety profile in elderly
patients with various somatic diseases. No adverse effects or rebound phenomena were recorded during treatment with cita-
lopram (Mackle 1998).
Several multicentric controlled studies assessing efficacy of citalopram in elderly patients have found significant improve-
ment of confusion, irritability, anxiety, depressive mood and psychomotoric agitation in patients treated with 10-30mg citalo-
pram daily. Efficacy of citalopram is significantly higher than placebo. Citalopram has not only antidepressive but also mood
stabilizing effect (Gottfries 1992, Gottfries 1999).
Our study has shown important role of SSRIs and especially citalopram in treatment of depressive symptoms. There is evi-
dence on efficiency of citalopram in treatment of major depression or depressive symptoms of Alzheimer dementia (DAT).
Our study has found citalopram (at daily dose of 20 mg) as the most frequently used and best tolerated antidepressive drug.
Citalopram did not cause sedation, retention of urine, orthostatic hypotension, and was well tolerated in drug-drug interactions.
Improvement of emotional disturbances, apathy, irritability, anxiety, depressive mood and psychomotoric agitation was ob-
served in patients treated with citalopram. Adverse effects were found to be minimal and reduced by half dose of SSRI given
during first week of treatment. No significant drug - drug interactions were recorded during treatment with citalopram.
Assessment of GDS, HAMD, CGI was not the aim of the study. The baseline assessments were used as inclusion criteria and
evaluation criteria of adverse events. This could be considered as weak point of the study and need to be completed in new study.

CONCLUSION
Depression is very common inelderly people and some people with Alzheimers disease are suffering from depression too.
Early diagnostic and adequate treatment of depression in elderly is very important.
In our retrospective assessment we studied 58 depressive patients with or without dementia and the most frequent and the
best tolerated antidepressant was citalopram.

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Baldwin RC, Chiu E,Katona C, Graham A: Guidelines on Depression in Older People,Practising the Evidence, 2002,
157:7-39,39-47,57-95
Balldin J,Gottfries CG, Karlsson I, Lindstedt G,Langstrom G,Svennerholm L: Relationship Between DST and the Serotonergic
Systm.Results from Treatments with Two 5-HT Reuptake Blockers in Dementia Disorders1988,International Journal of Geriatric
Psychiatry,Vol.3,17-26
Baumann P:Care of depression in the elderly: comparative pharmacokinetics of SSRIs,1998,Intemational Clinical
Psychopharmacology ,13 Suppl5:S35-S43
Boin A.:

89
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Cooke SC, Tucker ML: Geriatric Depression,2001,Journal of Pharmacy Practice,Vol.14 No 6,
Flicker C,Gottfries CG,Overa K: Citalopram Treatment of Depression in Elderly Patients with or without Dementia-Results
of a Placebo - Controlled Trial,dopilnit kedy a kde bol poster prezentovan
Foglia JP,Pollock BG, Kirshner MA et al: Psychopharmacology in Geriatric Populations, 1997,Psychopharmacology Bulletin
33/1/:109-112
Gottfries CG: Scandinavian experience with citalopram in the elderly, 1996 International Clinical Psychopharmacology, 11,
Suppl 1,41-44
Gottfties CG,Katisson I,Nynth AL: Treatment of Depression in Elderly Patients With and without Dementia Disorders,
1992,Intemational Clinical Psychopharmacology,6 Suppl. 5,55-64
Gottfries CG: Recognition and management of depression in the elderly ,1997,Intemationai Clinical
Psychopharmacology,12,supp1.7,S31-S36
Gottfries CG,Pollock BG: Citalopram:Its Use in Elderly Patients, Review, 1999,Annals of long-Term Care 7/51:181-189
Gottfries CG, Nynth AL: Effect of Citalopram,a Selective 5-HT Reuptake Blocker ,in Emotionally Disturbed Patients with
Dementia, 1990,kde to bolo pulikovan?
Guttierez M,Abramowitz Wattanapom: Steady-State Pharmacokinetics of Citalopram in Young and Elderly Subjects, 2000,
Psychopharmacotherapy, 20/12/:1441-1447
Hales RE,Yudovsky SC,Talbott JA: Textbook of Psychiatry, Second Edition, The American Psychiatric Press,562:313-353, 99-100
Hoschl C,Libiger J, vestka J: Psychiatric, 2002, 855:435-480
Ignjatovic D,Ignjatovic M.,
Jirk R,Zemkov P: Psychofarmaka pro pacienty vyiho veku, Remedia, 12,6/2002,425-440
Joubert AF, Sanchez C,Larsen F:Citalopram, 2000,Human Psychopharmacology, Clin .Exp.15, 439-451
Kasckow JW, Thalassinos A.Carroll BT: The Use of Citalopram to Treat Minor Depression in the Elderly, 2001,Poster
Presentation, AAGP
Katona C,Livingston: Comorbid Depression in Older People, 1997,79
Karlsson I: Pharmacologic treatment of noncognitive symptoms of dementia,1996, Acta Neurol Scand ,Supp1.165:101-104
Klysner R,Pleidrup E, Hansen HL, Poulsen DL: The Effectiveness of Citalopram in the Prevention of Depression Recureence
in Elderly Patients,2000,Poster Presentation, CINP
Koukolk F,Jirk R: Diagnostika a leni syndromu demence,Grada Publishing, 1999,152:22
Kurtzhaler I, Hotter A,Miller C,Kemmler G,et al: Risk Profile of SSRI s in Elderly Depressive Patients with Co-Morbid Physical
Iiiness,2001, 34,Pharmacopsychiatry,Short Communication
Kyle CJ,Hopfner Petersen HE, Overo KF: Comparison of the Tolerability and Efficacy of Citalopram and Amitriptyline in el-
derly Depresse Patients Treated in General Practice,1998,Depression and Anxiety,8:147-153
Kyle CH,Petersen HE Hopfner: Citalopram Treats Major Depression in the Elderly with Fewer Side Effects Than Amitriptyline,
2000,Poster Presentation, CINP
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Lovestone S, Gauthier S: Management of Dementia, 1999,161:12-13,20-2140-41
Mackie M,Gottfries CG: Citalopram Treatment of Noncognitive Symptoms in Elderly Demented Patients 1998,Poster
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Nynth AL,Gottfries CG,Smedegaard-Andersen L et al: A controlled multicenter clinical study of citalopram and placebo in
elderly depressed patients with and without concomitant dementia,1992 Acta Psychiatr Scand ,86:138-145
Opavsk: Strun prehled analgeticky innch leiv pro klinickou praxi, 12,6/2002,409-423
Pollock BG,Mulsant BH, Sweet R et al: Citalopram Pharmacotherapy for the Behaviorla Disorders of Dementia, 1998,Poster
Presentation, AMDA
Ragneskog H,Eriksson S,Karlsson I,Gottfries CG: Long-Term Treatment of Elderly Individuals With Emotional Disturbances:
An Open Study With Citalopram, 1996, International Psychogeriatrics, Vol.8, No4, 659-668
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90
 Table 1

Diagnoses overview
Diagnosis Number of patients
F.01 with depressive symptomatology 2
F.00.1 with depressive symptomatology 1
F.00.2 with depressive symptomatology 11
F.06.3 44

Table 2

Overview of antidepressants
Drug Number of AEs* Mean daily dose in miligrams
patients
Citalopram 42 5 20
Fluoxetine 1 1 20
Fluvoxamin 4 2 50
Paroxetine 3 1 20
Sertralin 7 2 50
Trazodon 1 0 75
Maprotiline 1 1 75
Venlafaxine 1 0 50

AEs* adverse events as number of patients

Table 3

Overview of neuroleptics
Drug Number of patients Mean daily dose in mg
Haloperidol 5 1.5
Risperidon 3 1
Tiaprid 5 100
Sulpirid 2 50
Zotepin 3 20,8
Olanzapin 1 2,5

91
 Table 4

Overview of anxiolyties
Drug Number of patients Mean daily dose in mg
Alprazolam 2 0,5
Bromazepam 4 3
Clonazepam 21 0,5
Hydroxizin 1 12,5

Table 5

Overview of ACHE inhibitors and nootropics

Drug Number of patients Mean daily dose in mg
Rivastigmin 8 11,25
Galantamin 1 16
Piracetam 23 2400
Ginko biloba 3 40
Others -vitamin E 14 400

92
THE EFFICACY OF DEPRESSION TREATMENT WITH MILNACIPRAN

(A six- MONTH EXPERIENCE)

Dana Ignjatoviov, M.D. (I)
Milan Ignjatovi, M.D. (2)
Silvia Beatriz Schweitzer, M.D. (3)

(1, 2) Private Psychiatric Outpatient Surgery, Cesta k nemocnici 1, Banska Bystrica,

Slovak Republic
(3) Psychiatric Department, Cespedes, Buenos Aires, Argentina

Summary
Depression represents one of the most frequent and grave psychical alienations. It manifests itself by tiredness, sleeping
malfunction, headaches, loosing or putting on weight, and failure of sexual function. Bad mood, however, is not necessarily the
most dominant symptom [G.N. Christodoulou, 2002].
It means that together with the establishment of the right diagnosis it is very important to manage an adequate treatment
of depression. Some of the key points, not only in the conditions of outpatient treatment, are anamnesis exploration of previo-
us depressive episodes, family anamnesis of affective diseases, and clinical exploration in relatives.
Depression today represents the 4th most frequent cause of health damage or loss of life due to early affection or morta-
lity. It is expected that depression will become the 2nd in 2020 [G.N. Christodoulou, 2002] .
In the U.S. A., yearlong prevalency represents 12.9% in women and 7.7% in men [Kessler et al., 1994]. In Europe, prevalency
is 17% [Lepine et al., 1997].
Our 6-month follow-up included 12 patients using milnacipran 100 mg per day. We made evaluations of HAMD and HAMA at
the start (it means on the first day of the follow-up) and used the CGI scale. Two patients were discarded from our follow-up:
one patient had discontinued the medication on her own in the 4th month of the course of treatment and the other one was
hospitalized due to a high risk of suicidal tendencies (HAMD-39 points, HAMA-28 points).
We have evaluated HAMD on the first day of treatment, then one month later, and then half a year after the setting up of
milnacipran 100-mg per day. In the 2nd month we did not observe any kind of strong amelioration (HAMD- 19.8 points), but in
the 6th month HAMD reached to 7.1 points.

Key words
Depression, BDRS (Hamilton Depression Rating Scale), CGI (Clinical Global Impression), milnacipran

Introduction
The development of new antidepressive drugs in last fifty years has come through the complicated way which was started
by the antidepressive effects discovery of iproniazid (an antituberculotic agent) in 1950 and irniprarnine (an antihistamine)
in 1955 [David J. Nutt, 2002].
The progress has finally resulted in the present very effective and strongly selective antidepressive medicaments
accompanied by a minimum of undesirable effects - venlafaxin, milnacipran [S.M. Stahl, 1997].
Tricyclic antidepressives (TCA) are strongly effective, especially in the treatment of harder depressions [P. Boyer and M.
Briley, 1998, S. A. Montgomery, 1999], but they are characterized by a large number of undesirable effects. At the same time, it
must be said that SSRI have at least the same efficacy as TCA [J. vestka, 1998].
SSRI are safer and better accepted by the patient. Nevertheless, they are not so effective for grave depressions [NI Briley,
1997], but they have their own exceptional position in the treatment of depressions, especially those connected with anxiety.
SNRI antidepressives are more effective compared with the effect of placebo in a big depression episode treatment [Y.
Lecrubier, 1997] and have the same effect as TCA, but they are much better accepted by the patient [Kasper, 1996].
The effect of SNRI in comparison with SSRI is almost on the same level [P. Boyer and M. Briley, 1998, M. Briley, 1997], but
their dual effect on noradrenergical and serotoninergical neurotransmission foreshadows higher effectiveness than in SSRI.
Thanks to this fact, SNRI have become very promising antidepressants [P. Boyer and M. Briley, 1998].
Depression represents a heterogeneous unit with a different variety of forms. It ranges from a light depressive episode,
through dysthymia to grave depression, which requires hospitalization [SA. Montgomery, 2001].
Symptoms of depression change according to the functional activity of the neurotransmitter system. Considering this, we
can divide the symptoms of depression into two groups. The first one is serotoninergic and the second one is noradrenergic. It
corresponds generally with the concept of impulsiveness, aggressivity, lower sexual appetence (5-HT system), and lack of mo-
tivation and energy (NA system), or when mixed, with anxiety, irritability, bad humour, and failures of cognitive functions
[S.A. Montgomery, 2001].
It means that antidepressives with a dual effect (venlafaxixt, milnacipran) show a theoretical promise to suppress, by their
dual effect, the symptoms of depression. The catecholaminal hypothesis [Schmidtkraut and Kety, 1967] assumes that depression

93
results from an insufficient activity of central noradrenergic neurons, whereas the indolarninal hypothesis [Van Praag, 1982]
talks about a deficit of the activity of central serotoninergic neurons [Monet, 1985].
Milnacipran is a new antidepressant inhibiting the reuptake of serotonin and nora.drenahne in vitro and in vivo without an
effect on the reuptake of dopamine. Microdialyses confirmed a higher extracellular level of serotonin and noradrenaline.
Milnacipran does not show any evidence of interaction with blown neurotransmitter receptors.
In comparison with TCA, chronic milnacipran administration does not modify the linkage to beta-adrenoreceptoral sites or
the function of the second messengers [P. Boyer and M. Briley, 1998].

Observed group and methodology

The group under observation included 12 patients. Woman (n= 8, average age = 41.33 years, age interval, 22y-60 years). Rwo
female patients were rejected out of the follow-up. One has discontinued the treatment at her own request (but not due to
undesirable effects) and the second one was hospitalized (HAMD-39 points, HAMA-28 points).
We have made HAMD and HAMA evaluations on the first day, then after one month and then in the sixth month of the follow-
up. We have evaluated CGI, too. All patients took milnacipran in a dose of 100 mg per day.

Criteria for insertion:

age 18 60 years
MKCH-10 and DSM-IV diagnostic criteria for an intermediately grave (F.32.1) to a grave episode of depression without
psychotic symptoms (F.32.2)
HAMD up to 18 points
6 months follow-up

Criteria for rejection:

comorbidity together with other psychical diseases
organic psychical affects
mania, hypomania
dysthymia
schizophrenia, schizoaffective failures
alcoholism and other kinds of dependence pregnancy
epilepsy in ananmesis
cardiac rhythm failures in anarnnesis
important somatic diseases
A certain shortage of this study could be a small group of patients in whom we observed the clinical status and evaluated
HAMD and HAMA scales. But we did not make MADRS evaluation, which is frequently used in control studies.
Another shortage of this paper is the duration of the study. The follow-up lasted only for six months and we did not make
HAMD and MAHA evaluations in the third month. There were only three evaluations - on the first day, after one month, and on
the last day of the follow-up.

Goals of study:
to compare the results of HAMD on the first day, after one month, and in the sixth month of the follow-up using milnaci-
pran in a dose of 100 mg pro die
to note any undesirable effect of milnacipran during a six months lasting follow-up

Results
We have included 12 patients into the follow-up, using the criteria of inclusion (Table 1). We used HAMD, HAMA (Table 2), and
CGI for the evaluation. We rejected two patients. The average HAMD on the first day of the follow-up was 21.5 points, HAMA-
15.4 points. After one month, the average was HAMD-19.8 points (only 1.7 points amelioration) and HAMA-12.4 points. After a
six-month follow-up, it was HAMD-7.8 points (13.7 points amelioration) and HAMA-7.1 points. Three of the 10 patients under
observation had already been treated for an episode of depression in the past. All of them used SSRI and anxiolytic agents.
In the patients we found the following undesirable effects: dryness in the mouth - 2 patients, dysuria - 3 patients, GIT trou-
bles 1 patient (Table 3). For complex evaluation of treatment efficiency, we used CGI (Clinical Global Impression).

Discussion
Clinical studies are a suitable source of information about new preparations, but physicians have to verify their effect when
prescribing them to patients [S.A. Montogomery, 1999]. Noradrenergic and serotoninergic neurons take the most important
part in the mechanism of the effect of neurons /S. Kasper, 2002/.
We can say that medicaments in which two or more synergic effects are combined together might have a higher therapeutic
effect and toleration comparable to the therapeutic mechanism of the effect of highly selective substances (S.M. Stahl, 1997].
Milnacipran is a cyclopropane derivative which inhibits noradrenergic and serotoninergic reuptake in the presynaptic area.
No activity of postsynaptic receptors was observed.

94
 The most frequently used dose is 50 rng of milnacipran two times per day [CM. Spencer and M. Wilde, 1998]. A dose of 100
rng of milnacipran pro die manifested a sufficient effect in our six-month follow up. Amelioration appears mostly in the second
week of therapy [Spencer and Wilde, 1998] with a daily dose of 100 mg (4 weeks - 3 months follow up). We observed not so
marked amelioration after one-month therapy (HAMD1=21.5 points, HAMD2=19.8 points - 1.7 points difference).
Milnacipran had an equal effect to those of imipramine and clomipramine, 150 mg pro die in Japanese patients [Spencer
and Wilde, 1998]. Milnacipran was less effective than clomipramine in our 6 months study.
A comparison was carried out concerning the effects of milnacipran 50-100 mg and 20 mg fluoxeloin pro die, 200mg flu-
voxamin pro die and mianserin 30-60mg pro die in the 4th and 12th week. Milnacipran had the same effect on hard depression
as TCA and SSRI during the 4-12 week follow-up. Milnacipran was very well tolerated with a minimum of undesirable effects -
dysuria 7% [Spencer and Wilde, 1998].
According to the study of Kasper et al., 1996, one of the most frequent undesirable effects during milnacipran therapy is
dysuria (2.1%). Pending our follow-up of undesirable effects occurrence, dysuria appeared in three patients, dry mouth in two
patients, tremor in two patients, gastrointestinal troubles in one patient, and obstipation in one patient. These results are com-
parable with the international studies [Spencer and Wilde, 1998; Kasper, 1996].
The reported undesirable effects did not result in discontinuation of milnacipran therapy. A very important thing for the
effect comparison of medicines is comparative studies, multicentred and placebo-controlled.
In our study we focused on the results of a six- month milnacipran therapy course in ambulatory conditions but we did not
compare it with placebo and SSRI. It would be desirable to do it in the future.
Several studies were published in the United States which covered 527 ambulatory patients (131 patients used milnacipran
25mg pro die, 130 patients used milnacipran 50mg pro die, 133 patients milnacipran 100mg pro die, and placebo was used by
133 patients).
The follow-up included HAMD results with more than 22 points (average entering HAMD in our study was 21.5 points),
MADRS, and CGI. The results of milnacipran 100mg per day were significantly better than placebo (p < 0.01). There were about
64% responding patients pending 8 weeks follow-up with a milnacipran dose of 100 mg per day [Y. Lecrubier, 1997].
The follow-up included 68 patients with a. milnacipran dose of 50mg in comparison with 49 patients treated with placebo
in Europe. HAMD was higher than 22 points and according to the results the differences were not statistically significant. [Y.
Lecrubier, 1997].
A milnacipran dose of 50mg in 29 patients and placebo in 29 patient were compared in the third study. Together there were
58 hospitalized patients and after 4 weeks follow-up HAMD changed from 18.7 to 7.1.
We observed HAMD, which at the beginning of study was 21.5 points. After a month, HAMD became 19.8 points, which me-
ans only 1.7 points amelioration. At the end of the 6th month, HAM was 7.8 points. Amelioration was thus 13.7 points compared
with the first day of the follow-up.
We also evaluated global clinical impression. The grade of illness importance on the first day of the follow-up: intermediate
(6 patients), hard (4 patients). Grade of illness importance at the end of the 6th month was: normal, no evidence of illness (5
patients), marginal evidence of illness (5 patients). Very kacaig global amelioration appeared in all 10 patients.
During the four months lasting follow-up of patients with a milnacipran dose of 50mg per day, all patients were evaluated
as very clearly ameliorated [Rouillon, 2000]. Although a group of 10 patients is small, the results show that our experience is
comparable to the studies made in the US and Europe (France and Sweden), which demonstrate that new SNRI medicament
specifically affecting serotonin and noradrenaline are more effective on hard depression than SSRI and possess the same effect
as TCA with a smaller number of undesirable effects [Briley, 1998].
Another six-month study made on a small group of 41 patients and comparing 100mg milnacipran to 75 mg clomipramine
showed a 50% reduction of HAMD. But there were no significant differences in MADRS and CGI scales [P. Boyer and M. Briley,
1998].
Many studies confirmed milnacipran effectiveness in the therapy of depression compared to other antidepressive agents
[Hindmarch,1997, Kasper, 1996, Spencer, 1996].
These published studies helped us to understand the theoretical basis of milnacipran role in hard depression episode tre-
atment which we verified in practice.

Conclusion
Depression is very a heterogeneous unit [S.A. Montgomery, 2001]. It has various manifestations requiring complex and
adequate antidepressive therapy.
Mihiacipran exerts its effect on basic depression symptoms including anxiety, sleeping malfunction, and psychomo-
toric retardation. It does not affect memory functions.
Milnacipran does not have any interaction via the cytochromic system P-450 and could be effective in patients with conco-
mitant pharrnacotherapy. It does not affect the cognitive functions and that is why it is very suitable for the use by older and
anxiety patients. Although it has no sedative effect, it adjusts sleeping malfunctions.
Milnacipran seems to be a safe, well tolerated, and highly effective antidepressant in the treatment of intermediate to hard
depressive episodes with minimal undesirable effects.
It depends on our clinical experience whether milnacipran will become the medicament of the first line in depression tre-
atment [SA. Montgomery, 1999].

95
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HAMD, HAMA Scores

after one month of milnacipran

1st day of study after six months of milnacipran study
therapy
HAMD HAMA HAMD HAMA HAMD HAMA
1. 24 22 22 20 12 10
2. 25 23 18 18 11 6
3. 23 18 18 18 10 15
4. 18 8 16 8 6 6
5. 18 8 10 6 6 6
6. 18 10 16 10 8 6
7. 18 7 12 7 6 5
8. 25 10 18 10 0 0
9. 18 10 6 6 5 12
10. 18 38 22 21 12 11
ave-rage 21.5 15.4 19.8 12.4 7.8 7.1

96
Table 1 PATIENT LIST
Number Avg.age
Men 4 44.25
Woman 6 40.66
Total 10 41.33

Table 2 HAMD, HAMA Scores

after one month of milnacipran after six months of milnacipran
1st day of study therapy therapy
HAMD1 HAMA1 HAMD2 HAMA2 HAMD3 HAMA3
Avg.points 21,5 15,4 19,8 12,4 7,8 7,1

Table 3 List of undesirable effects of medicament

Vertigo 0
Dry mouth 2
Anxiety 0
Obstipation 1
Dysuria 3
GIT malfunctions 1
Tremor 0
Palpitation 0
Nausea 0
Somnolence 0

97
THE RISK OF SUICIDE IN THE GERIATRIC PATIENTS COMMUNITY

AUTHORS
Dana Ignjatoviov1 M.D.
Milan Ignjatovi2 M.D.
Michala Knikov3 Mgr.
1, 2, 3 - Non governmental psychiatric health clinic, Cesta k nemocnici, 97401 Bansk Bystrica, Slovak republic

Abstract
Depression occurs quite often at the older age. The base of the depressive disorder is panthic mood, sadness, reduction of
the interest sphere and initiative... In the group of geriatric patients the suicidal thoughts occur very often. They have various
thoughts: about fear of death, thinking that it would be better to be dead, the life is not worth to live, up to the precise suicidal
plans/suicidal tendencies, or suicidal attempts (Hoschl et al., 2002).
In the study we have included 14 gerontopsychiatric patients placed in retirement home in Bansk Bystrica and 14 gerontop-
sychiatric patients who do not live in retirement home. They live at home and they are the patients from our psychiatric clinics.
In both groups of the patients we have examined the age, gender, social conditions, degree of education, and occurrence
of chronic diseases (somatic). The questioner was used to evaluate the depression - incoming record of the depression - VSTD
(Filip - 1997), Geriatric depression scale (GDS) and Becks selfevaluation scale to evaluate the depression.
All of the patients from the retirement home had good social conditions and they had mostly elementary education.
In the group of patients who do not live in the retirement home the social status was assessed as excellent and the level of
education was higher - college degree and high school diploma.
In spite of our expectations, suicidal thoughts occurred with the same frequency even in the group of the patients who do
not live in the retirement home. Even though they have better score in the elevation of depth of the depression (GSD, Beck).
Everyone in the group A, 14 gerontopsychiatric patients from retirement home, was treated for symptoms of depression. Five
patients had suicidal thoughts, even though all of the patients were monitored and treated for one or more chronic diseases.
Group B consisted of 14 gerontopsychiatric patients who do not live in the retirement home. Six patients had suicidal tho-
ughts, even though all of the patients were monitored and treated for one or more chronic diseases.
Among major risk factors of depression and suicidal thoughts are emotional problems at the older age and anxiety (Beurs,
1999, 2001) associated with the partners or close persons death, illness, loss of the job and change of the home, for example:
placement in the retirement home.
We have also endorsed environmental stresors as risk factors of depression and suicidal thoughts in the older age.
key words: older age (+55 years of age), suicidal thoughts, social conditions

Introduction
The diagnosis of depression is very common in the older age and requires besides patient approach also necessary amou-
nt of the knowledge. Problems with the appetite, change of body weight, insomnia, psychomotor agitation or retardation, loss
of energy, feeling of useless, guilt, problems with the concentrations, thoughts about death or suicide or suicidal attempts are
serious signs of the depression (Hoschl et al., 2002).
Depression in the older age is quite often misinterpreted or overlapped by somatic illness, since the patients suffer from
one or more chronic diseases (Smolik, ).
It is important to distinguish problems with the memory within depressive feelings from starting or from advanced dementia.
Higher prevalence of depression was observed in females, who are even more often treated (Beekman et al., 1999). However,
in males the depression is more serious risk factor of mortality (Zeng et al., 1997). Chronic depression was not associated with
higher mortality of the patients. Based to Jorm et at. it is quite possible that depression is prodrome of cardiovascular diseases
or dementia or occurs more often in these conditions (Jorm et al.,2000).
Among risk factors of mood disorders (according to WPA, PTD, Educational Program on Depressive Disorders, 1997) are
included: divorce, loneliness, being widowed, depression in the past, family history of depression, bad life experiences, drug
abuse, somatic disorder, social isolation, poor personal life, changes in social systems, pharmocogenic influence, changes in in-
terpersonal relations (Hoschel et al. 2002).
Alarming fact is the finding that the most suicides occur in the group age over 70 years of age, and the strongest predic-
tors of suicidal behavior are the presence of suicidal attempts in the medical history and hopelessness (Hoschel el al., 2002).

Method and group characteristics

Examined group consisted of:
14 gerontopsychiatric patients form retirement home treated for symptoms of depression (group A)
14 gerontopsychiatric patients living at home and they were not place in to the retirement home (group B) and they are tre-
ated for symptoms of depression in doctors office.
In both groups of the patients we have examined the age, gender, degree of education, socioeconomic conditions, and fa-
mily status. The questioner was used to evaluate the depression - incoming record of the depression VSTD (Filly - 1997).

98
 We have examined the depressiveness using GDS (Geriatric depression scale) and by Becks selfevaluation scale to assess
the depression. We have examined occurrence of suicidal thoughts during actual psychiatric evaluation as well.

Inclusion criteria:
age over 55 years
symptoms of depression
life in a community (retirement home) or in previous home
occurrence of one or more chronic somatic diseases

Exclusion criteria:
delirium
multiple personality
psychotic disease
additions

Goals of the study:

To compare socioeconomic and family conditions in patients living in the retirement home (group A) and in patients living
individually at home (group B) and their influence on the occurrence of suicidal thoughts.
To evaluate and compare the experience of depression in the patients living in retirement home (group A) and in the pa-
tients living individually at home (group B).

Null hypothesis
Occurrence of suicidal thoughts and depression is greater in the patients placed in the retirement homes in comparison
with the patients living individually at home and is associated with their living and socioeconomic conditions.

Results
Our results did not prove the null hypothesis.
Suicidal thoughts have occurred equally in patients placed in the retirement home (5 out of 14 patients) just as in the pati-
ents living individually (6 out of 14 patients, Table 7).
In the group of patients living in the retirement home, the living conditions were evaluated as good ones, in the group of
patients living individually as excellent (Table 3).
Marital status is presented in Table 2, education is accessible in Table 5 and employment list is in Table 4.
Listing of the diagnosis is presented in Table 6.
Results of the test of depressiveness are summarized in Table 8.

Discussion
Depression is one of the most often occurring disorders in the older age. Depression very often imitates some of the so-
matic diseases (Hoschl et al., 2002). Great risk represents suicidal thoughts, which can lead to suicide, especially in the older
patients. Suicidal attempts occur three times more often in females than in males. Males commit suicide three times more of-
ten than females.
In the present group, one patient placed in the retirement home attempted to commit suicidal. The patient attempted to
commit suicide in the past, before his/her placement in the retirement home.
It is alarming that the number of suicides is increasing in a group of people over 70 years of age. The average age of the pa-
tients in the group A was 79.85 years of age and in the group B - 66.85 years of age. With increasing suicide are associated such
demographic factors as social isolation, childlessness, not sufficient social integration, serious somatic illness and etc. (Hoschl
et. al. 2002). This finding has been also supported by the results from our group of patients.
In the group B of patients living in retirement home were more widowed patients (9 patients) and 2 single people. in the
group A (living individually at home) were more married patients (7 patients), only 4 patients were widowed.
All of the patients were retired, except for one who was working (patient from group A).
More studies have shown that clinical depression or depression symptoms are risk factors for higher mortality (from car-
diovascular disease) in the sample of psychiatric patients (Kaarin et. al., 2002).
All of the included patients are treated for one or more somatic chronic disease.
Factors, which lead into depression and mortally in non-psychiatric community were chronic somatic diseases, low BMI,
cancer, hear disease, smoking, alcohol abuse.
What is interesting is that the depression leads to coronary disease in the middle age in comparison to the older population
(Mendes de Leon, 1998). This finding is probable in our group of patients, since prior to the diagnosis of the depression, all of
them were treated for cardiovascular disease. Therefore, cardiovascular disease was not the result of the depression.
All of the patients included into our study suffered from one or more chronic disease, mostly with cardiovascular disease
and vertebral problems of the kinetic apparatus. No one from the examined group had psychiatric treatment in the past. One

99
patient had psychiatric examination, after repeated suicidal attempts, however, without recommended psychiatric medication
or psychotherapy.
The study, which was examining patients with the diagnosis of depression or with the symptoms of depression with or wit-
hout chronic illnesses showed that the patients with poor psychic status, poor social functioning had greater physical pain and
the depression was more severe (Wells et. at 1989). Among our patients we have found that the experience of depression was
significantly associated and influenced by these factors. Occurrence of suicidal thoughts was comparable in both groups, living
in retirement home (group A) and living individually at home (group B). The experience of depression was worse in the group
B, living in the retirement home, GDS = 10 points, in comparison to group A GDS = 7 points and Becks = 13 points in group A
and Becks = 8 points in group B.
Long term therapy of the depression is recommended especially in the hospitalized patients (Paykel, 2001). There are se-
veral two and more years placebo controlled studies for prevention of recurrence of the depression (Montgomery et. al., 1993,
Rouillon et. al. 2000).
Unfortunately many studies conducted with older patients do not take into the consideration their social adaptability
(Reynolds et. al., 1999), which significantly influences their experience of the depression. This has been demonstrated in the
group A of the patients living in the retirement home.
Mental stress, marital status, socioeconomic conditions, chronic illness and as well as the age are often the causes of the
depression at the older age (Katona et at., 1997). Social isolation, placement into a new surroundings (retirement home), child-
lessness, evaluation of the meaning the life often lead to suicidal thoughts, and this is only a step from suicidal actions. This
borderline is very unclear (Hoschl et al., 2002).

Conclusion
Depression represents serious mental problem. It requires besides appropriate diagnostic measures also high quality and
long term psychopharrnaco and psychotherapeutic approach (Briley et al., 1998). Active questions concerning the experience
of the depression and suicidal thoughts will help us to intensify and improve the patients therapy.
Intensive and fiddly work of the staff in the retirement home as well as the correct psychopharmacotherapeutic and
psychotherapeutic approach to the gerontopsychiatric patients may significantly improve the quality of life and enhance the
moments of the senescence.
In conclusion we would like to thank Livia Lapansk, the head nurse in the retirement home and as well as the actual inha-
bitants of this establishment in Bansk Bystrica who have made possible to carry out this epidemiological investigation.

References
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Psychiatry,1999,174:307-311
De Beurs E,Beekman AT, Balkom AJ,Deeg DJ,R van Dyck,W van Tilburg:Consequences of anxiety in older persons:its effect
on disability,well-being and use of health services,Psychol Med 1999, 29/3/:583-593
De Beurs E,Beekman A,Geerlings S,Deeg D ,R van Thick, W van Tilburg:On becoming depressed or anxious in later life-simi-
lar vulnerability factors, but different effects of stressful life events, The British Journal of Psychiatry, 2001,179:426-431
Boin A A:Linost i stres,oseaj koherentnosti i prevladavanja stresa u uslovima
drutvene krize,2001,Vrac, 251
Briley M, Montgomery SA:Antidepressant Therapy at the Dawn of the Third Millenium, Martin Dunitz LtD,1998,349:307-319,319-333
Filip V et al.: Praktick manual psychiatrickch posudzovacich stupnc, 1997, 185:95-117
Hoschl C,Libiger J,vestka J: Psychiatrie,2002,895:234-235,435-452,638-641
Jorm AF:Is depression a risk factor for dementia or cognitive decline? A review.Gerontology,2000,46:219-227
Kaarin J A,Luszcz AM: Mortality Risk Varies According to Gender and Change in
Depressive Status in Very Old Adults,Psychosomatic Medicine, 2002,64:880-888
Katona C,Livingston G:Comorbid Depression in Older People,Martin Dunitz Ltd,1997,79
Mendes de Leon CF,Krumholtz HIVI, Seeman TS,Vaccarino V,Wiliams CS,Kasl
SV,Berkrnan LF:Depression and risk of coronary heart disease in elderly men and women:New Haven EESE,1982-1991,Established
Populations for the Epidemiologic Studies of the Elderly. Arch Intern Med., 1998,158:2341-2348
Montgomery SA Dunbar G:Paroxetine is better than placebo in relaps prevention and the prophylaxis of reccurent depre-
ssion.Int Clin Psychopharmacol.,1993,8:189-195
Nutt D,Feeney A,Argyropolus S:Anxiety Disorders Comorbid with Depression:Panic disoorder and agoraphobia,Martin Dunitz
Ltd , a member of the Taylor and Francis Group, 2002,108
Paykel ES :Continuation and maintenance therapy in depression, British medical Bulletin,2001,57:145-159
Reynolds CF,Frank E,Perel JM et al :Nortriptyline and interpersonal psychotherapy as maintenance therapies for reccurent
major depression: a randomised controlled trial in patients older than 59 years.JAMA,1999,281:39-45
Rouillon F,Berdeaux G,Bisserbe JC et al: Prevention of reccurent depressive episodes with milnacipran consequences on
quality of life, Jaffect Disord,2000,58:171-180
Wells KB, Stewart A,Hays RD,Bumam MA,Rogers W,Daniels M,Berry S,Greenfield S, Ware J: The functioning and well-being
of depressed patients.Results from the Medical Outcomes Study, JAMA, 1989,262/7/:914-919
Zheng D,Macero CA, Croft JB,Giles WH,Davis D, Scott WK:Major depression and all cause mortality among while adults in
the United Mates, Ann Epidemilo., 1997,7:213-218

100
 Table 1

Group A Group B
Average age 79.85 (67 90) 66.85 (59 70)
Gender females N = 10 out of 14 females N = 9 out of 14
*Group A= gerontopsychiatric patients placed in the retirement home *Group B= gerontopsychiatric patients living individually at home

Table 2

Marital status Group A Group B

Single 2 0
Married 1 7
Divorced 2 3
Widowed 9 4
Total 14 14

Table 3

Present social conditions of Group A Group B

the patient
Excellent 0 11
Good 14 3
Poor 0 0
Total 14 14

Table 4

Employment Group A Group B

In the household 0 0
Studying 0 0
Manually non-qualified 0 0
worker
Manually qualified worker 0 1
Clerk 0 0
Clerk in leading position 0 0
Disable retired senior 0 0
Retired senior 14 13
Other 0 0
Total 14 14

Table 5

Degree of education Group A Group B

Unfinished elementary school 5 0
Elementary school completed, 6 3
further not qualified
College diploma 2 6
High school diploma 1 5
University 0 0
Other 0 0
Total 14 14

101
 Table 6

Diagnose Group A Group B

F.01 with symptoms of 1 0
depression
F.00.2 with symptoms of 2 0
depression
F.06.3 10 5
F.07 1 0
F.32 0 8
F41.2 0 1
Total 14 14

Table 7

Suicidal thoughts Group A Group B

5 6

Table 8

Evaluating scales Group A Group B

GDS (geriatric depression 9.64 points=10 (5-14) 6.71 points=7 (0-11)
scale)
Becks selfevaluating scale of 12.5=13 points (2-25) 8 points (2-17)
depression

102
THE QUALITY OF LIFE IN PATIENTS WITH DEMENTIA OF ALZHEIMERS
TYPE LIVING IN OLD PEOPLES HOMES AND NURSING HOMES

AUTHORS
MUDr. Dana Ignjatovi, 1
MUDr. Milan Ignjatovi, 1
Mgr. Michala Knikov, 1
MUDr. Tibor Baka, 2
Dr. Silvia Beatriz Schweitzer, 3

Psychomed Svtosvsky, Bansk Bystica, the Slovak Republic

Institution of Epidemiology JLF, Martin, the Slovak Republic
Buenos Aires, Argentina

Abstract:
The quality of life of the patients with Dementia of Alzheimers type (DAT) in Old peoples homes and Nursing homes is de-
termined by different factors, not only endogenous. Even though there is a documented impact on the quality of life of the pa-
tients, this problem is not closely monitored in our conditions and therefore we will focus on it in our work.
Cognitive symptoms in dementia are rather frequently accompanied by anxiety, depression, delusions and hallucinations
(Latas, 2003).
One of the biggest problems in taking care of the patients with Dementia of Alzheimers type is just a problematic behaviour
of the patients (not adequate verbal or motoric activity) (Stegaru, 2003).
We have included 19 patients with the diagnosis of Dementia of Alzheimers type and 25 patients without a psychiatric dia-
gnosis into the follow-up. All the patients were from two Old peoples homes and Nursing homes in Bansk Bystrica and there
was not a difference between the average age of the patients.
The an of this study was to evaluate and compare the quality of life of the clients with Dementia of Alzheimers type and the
clients without any psychiatric burden living in Old peoples homes and Nursing homes in Slovakia.
The results of this pilot study confirmed that the quality of life in patients with Dementia of Alzheimers type is lower com-
pare to the clients without any psychiatric burden living in Old peoples homes and Nursing homes.
We have monitored and evaluated following scales and questionnaires in these patients:
ADL - Activities of Daily Living
IADL - Instrumental Activities of Daily Living
CRICHT - Crichton Geriatric Rating Scale
SLAG - Sandoz Clinical Assessment Geriatric Scale
NOSGER- Nurses Observation Scale for Geriatric Patients
There were significant differences except the mood in all evaluated items. The patients with the diagnosis of Dementia of
Alzheimers type represented more severe patients in all these items whose self-sufficiency in ADL and IADL was lower compa-
re to the patients without any psychiatric burden. In spite of the fact that we have excluded the patients with the severe form
of Dementia of Alzheimers type from our follow-up, the entry score and results in an area of cognitive disorders, also the in-
terpersonal relations and physical dysfunctions were worse in these patients.
Better results were obtained in the clients without any psychiatric burden. In a part dealing with the apathy and in a part de-
aling with the mood there was not any significant difference which would prove the fact that even the clients without psychia-
tric burden living in an Old peoples home and a Nursing home are more frequently liable to depressive experience (anxiety,
depressive mood and lack of motivation).
This study represents a pilot study for other similar studies of this kind in Slovakia.

Key words:
The quality of life in patients with Dementia of Alzheimers type and without any psychiatric burden in Old peoples homes
and Nursing homes, ADL, IADL, CRICHT, SCAG, NOSGER.

Zero hypothesis:
There is not any difference in the quality of life of the patients/clients with the diagnosis of Dementia of Alzheimers type (mild
and moderately severe degree) and the clients without a psychiatric diagnosis living in Old peoples homes and Nursing homes.

Alternative hypothesis:
Dementia of Alzheimers type is related to lower quality of life of the patients compare to the clients without any psychia-
tric burden who live in Old peoples homes and Nursing homes.

103
Group of patients (Subjects):
The dwellers of two average standard Old peoples homes and Nursing homes in Slovakia were included into the study; into
the control study the clients were selected by the systematic selection according to an alphabetical list of the facility dwellers,
the first twelve clients from one facility and the first thirteen clients from the other one. Because this was not a case of an inva-
sive intervention which does not change the quality of life of the patients, the physicians approval of the self-government for
a follow-up conduct was not necessary.
The patients agreed with the filling in the questionnaire implicitly. The information about the purpose, the paint of the stu-
dy, assurance about the anonymity and observance of medical ecrecy within the study into which they voluntarily agreed to
participate was a part of it. The xecutives of Old peoples homes and Nursing homes and head nurses, who actively articipated
in a follow-up, agreed with the performance of the follow-up.

Inclusion criteria:
mild and moderately severe degree of Dementia of Alzheimers type
age over 65 years
a patient capable of participation in a follow-up (questionnaires) and willing to
cooperate
placement of the patient in an Old peoples home and a Nursing home

Exclusion criteria:
severe degree of Dementia of Alzheimers type
other psychiatric diagnoses
severe somatic illnesses

Used tests:
ADL (Activities of Daily Living)
IADL (Instrumental Activities of Daily Living )
CRICHT (Crichton Geriatric Rating Scale)
SCRAG (Sandal Clinical Assessment Geriatric Scale)
NOSGER (Nurses Observation Scale for Geriatric Patients)

Introduction:
Alzheimers type of dementia belongs among the most frequent degenerative diseases of the brain (Smolik, 1996). It is also
one of the most frequent cases of death. It is ranked on the fourth place after cardiovascular diseases, malignants and acu-
te cerebrovascular accidents (Pidrman, Bouek, Ltalov, 2003). And it is also becoming a severe medical and social problem.
The most finances are used for the in-patient care of the demented patients. Supporting programmes for the care-givers of
the patients with dementia, which arise in many centers specializing in diagnostics and treatment of cognitive disorders, are
rather important (Kurz, 2003).
The quality of life in a society is evaluated by several measures; one of them is also increasing average age of life and su-
bsequently the number of inhabitants older than 65 years of age as well. With the increase of age there is also the increase in a
risk of psychiatric disorders (cognitive decrease, depressive disorders, delirium, behavioral symptoms ...), as well as cardiovas-
cular and neurological diseases (conditions after acute cerebrovascular accidents).Immobility of the patient and incontinence
are often associated. This kind of patient is rather demanding as for the care, since considering the comorbidity he becomes
the big burden for the care-givers. These patients often live in Old peoples homes and Nursing homes.
As long as the care-giver or the relative of the demented patient is not educated enough, he can perceive the behaviour
of the patient as rather disturbing, many times as though he was doing the things on the purpose- repeats the activities, he
does not know what he was told a while ago, as soon as he finishes the breakfast he starts verbal attacks that he was not given
anything to eat, he does not recognize his own partner, accuses his children that they took his money, messed up with perso-
nal things and clothes ...
Even the least probable attacks of demented patient can be badly tolerated by the care-giver and also the relatives.

Results:
We have included 19 patients with the diagnosis of mild and moderately severe degree of Dementia of Alzheimers type
(DAT) into the pilot study. The control group comprised of 25 clients without any psychiatric burden. All of them represented
the dwellers of the Old
peoples homes and Nursing homes (OPS and NH). Because the clients were chosen from two average OPS and NH, a selec-
ted sample of people is possible to consider as a representative one. The age is one of the determinants of the quality of life,
in a monitored sample there was not a difference between the average age in one and the other group, so it was not necessary
to take into account a potential concurrent impact of the age. There were more women than men in both groups. In an evalu-
ating scale ADL (Activity of Daily Living) more than 64% clients (i.e. 16 clients out of 25) without any psychiatric burden were

104
completely self-sufficient (6b/6b). However, only 5 patients (i.e.25%) out of 19 with Dementia of Alzheimers type were totally
self-sufficient.
In an evaluating scale IADL (Instrumental Activities of Daily Living) only 3 clients (8b/8b) were fully sells-sufficient from
the group without any psychiatric burden and none of the patients with DAT reached a complete self-sufficiency. 8 patients
with DAT were not totally self-sufficient and none of the clients without any psychiatric burden. We have used a CRICHT scale
(Crichton Geriatric Rating Scale) for an evaluation of the impact of the treatment on patients behaviour. This scale evaluates
mobility, orientation, communication, cooperation, uneasiness, and self-service activities getting dressed and eating, inconti-
nence,. sleep, and mood objectively and subjectively. 17 clients without any psychiatric burden reached the score value from 10
to 20 points which indicates a mild deterioration, only one client reached the score of 31 points which reflects a severe deteri-
oration. In patients with DAT 8 patients reached the score over 31 points and only 6 patients had a score indicating a mild dete-
rioration which would represent the fact that the patients with DAT have more problems with communication, are less mobile,
suffer from sleep disorders and incontinence more often.
Geriatric scale of the firm SANDOZ SCAG (Sandoz Clinical Assessment - Geriatric) is used especially in the in-patient con-
ditions or facilities for pensioners with the aim of observing the changes in a course of therapy. We have assessed 5 monitored
variables: cognitive disorders, interpersonal relations, mood, apathy and physical dysfunctions. In the first assessed item - co-
gnitive disorders a significant difference appeared in both groups. Confusion reached moderate intensity in symptoms (3 out
of 5 points) even in a group of clients without any psychiatric burden.
In a second assessed item - mood - a significant difference did not appear between both groups which would indicate more
depressive experience even in clients located in OPH and NH who are not psychiatrically cured. The lack of motivation and
anxious experience were the most distinct within this item in both groups of dwellers from OPH and NH. In the third assessed
item apathy - there was present a significant difference between both groups. In the fourth item - interpersonal relations
- there was also significant difference between both groups. The listlessness to the surrounding was the most substantial in
the group of clients without any psychiatric burden. In the fifth assessed item - physical dysfunctions - a significant differen-
ce between both groups was also present. The last scale which we used was the NOSGER scale (Nurses Observation Scale for
Geriatric Patients). This assessment was interesting in a fact that according to assessments of nurses the clients without any
psychiatric burden spoke more frequently that they are sad, useless, were anxious at night, they repeated the same thought in
conversations more often, looked sad or weepy, they were irritable or argumentative more often when someone asked them
something, they were more aggressive (verbally and in an action as well), they were stubborn, did not care about the instruc-
tions or rules compare to the patients with DAT. The nurses agreed on the fact that both groups look clean and tidy. The pa-
tients with DAT left their rooms inappropriately dressed more often, had difficulties to shave and comb themselves without
any help, did not pay attention to their interest and hobbies, did not even watch TV programmes, they got into touch with the
persons in their surroundings less often
Age comparison p=0,255253 There is not any difference between the average age in the 1. and the 2. group so it is
necessary to take into account the potential concurrent impact of the age.
Evaluating scales ADL IADL CRI SCAG-KF SCAG-IV SCAG-N SCAG-A SCAG-
TD
Average of the 1. 5,52 5,00 19,64 2,32 1,80 2,12 1,80 1,96
group
Average of the 2. 4,16 2,95 30,16 3,58 2,79 2,74 2,63 2,63
group
Difference among 1,36 2,05 10,5 -1,26 -0,99 -0,62 -0,83 -0,67
the averages

(Students t-test) p= 0,003658 0,005501 3,11 0,003708 0,00313 0,087398 0,025471 0,03971
E-05
.

Discussion:
It is rather important and at the same time a difficult task to assess the quality of life of the patients suffering from DAT li-
ving in OPH and NH. The research of the quality of life involves conceptual and methodological challenges (Brod, 2003). It is
important to answer the questions what quality of life actually is in demented patients, by which variables it is defined and cha-
racterized, what we perceive the most on the patients behaviour and what impact it has on the interaction between the pati-
ent with DAT and care-givers.
Behavioral management of behavioral disorders in Dementia of Alzheimers type represents the most frequent intervention
in a clinical practice. Disturbing behaviour is also a result of an interaction between the specific behaviour of the patient and a
reaction of the care-givers (Lovestone, Gauthier, 2001). Such behaviour has an impact on the quality of life not only of the pati-
ent with DAT but also on his care-giver. There is a great number of studies that deal with the meaning of cooperation between
the patient with DAT and a care-giver (Stegaru, 2003; Purandare, 2003; Wettstein, 2003). Bonnin - Guillaume (2003) suggested

105
in their work that nurses were considerably tolerant against the agitated behaviour, and it did not get worse even in demented
patients. A significant fact is that a physical and also verbal aggressive
behaviour was worse tolerated in both groups of demented and non-demented patients. Even the lower quality of life was
related to behavioral disorders.
Rodriguez et al. (2003) addressed psychological and social aspects in a management of patients with DAT in their work. They
carried out the studies among the care-givers of 120 patients with the diagnosis of Dementia of Alzheimers type in a period
of time from January 2001 until December 2002. All of the care-givers responded to a 50-item questionnaire related to social
characteristics of the patients family, family relationships, private and public health care and a family psychological distress.
Problems with the sleep, anxiety and depression depended on the quality of life of the patients with DAT. In another study by
Novell et al.(2001), they compared the assessment of the quality of life in a sample of 76 patients with DAT, as it was assessed
by themselves and their relatives though 17-item Duke profile of health. This study is an important source of information about
the quality of life of the patient with DAT. Statistically significant differences were recorded in the main score in some dimen-
sions where the patients and their relatives talked about lower quality of life which similarly came out in our studies, although
we have used other evaluating scales for this assessment.
Another works of Wimo, Winblad a Grafstrom (1999), referring to social consequences of DAT and a long term-care, show
that dementia represents a future problem and that the average age is increasing along with the number of patients with DAT.
Tereza Gonzlez - Salvator et al. (2000) were engaged in the quality of life in demented patients in a long-term care, 32 nurses
were asked about the quality of life of 120 patients in a long-term care who met with the diagnostic criteria of DSM-IV for de-
mentia. Hospital physicians revealed better quality than they expected (assumed).
Tereza Gonzlez Salvator et al. (2000) report that interventions which could improve better orientation, physical capabili-
ties just like cholinomirnetic treatment does, psychosocial intervention or behavioral strategies could also be in a future rese-
arch on the quality of life.
A rather interesting study was carried out in England where the authors focused on the quality of care provided for the pa-
tients with dementia. The aim of the study was to review the experience with a temporary care of the persons with dementia
who lived in small groups in six Old peoples homes run by two large voluntary organizations in England. The methodology of
Dementia Care Mapping (DCM) was used for detection of the feeling of well-being, health in persons with dementia and for in-
vestigation of the range of their psychosocial needs dementia mapping included monitoring of the quality and also the quantity
of behaviour (Innes, Surr, 2001). This work is inspiring also for other works in Slovakia, and it confirms that the behaviour of the
demented patient significantly influences his quality of life and it significantly affects care-givers of the demented patients as well.
Jason Karlawish et al. (2001) compared global quality of life of the patients with DAT in their work by using of the direct and
substitute appraisal of the quality of life of the patients and their guardians. 20 patients with moderately severe and 11 patients
with mild Dementia of Alzheimers type were included into the follow-up. Nearly half of the guardians of the patients with DAT
reviewed the quality of life in a different way compare to the fact how it was expected among the patients. We have focused in
our work on the assessment of the quality of life of the patients with DAT living in Old peoples homes and Nursing homes. We
have used different scales. The NOSGER scale, the results of which we have already described, was among them.
Validity and reliability of the NOSGER scale (Nurses Observation Scale for Geriatric Patients) were described by Wahle,
Haller a Spiegel (1996) in their work. They portray the purpose of the NOSGER scale filled up by the nurses or care-givers. It
works with daily behaviour of geriatric patients with the emphasis on 6 subsequent areas (dimensions): memory, instrumental
activities of daily living (IADL), ordinary daily activities (activities of daily living - ADL), mood, social behaviour and intrusive be-
haviour. We have focused just on these areas in our study.
Presented validity study comprises of 50 healthy elderly subjects, 25 patients with moderately severe dementia, 25 patients
with progressing dementia and 25 elderly patients with depression. NOSGER was filled in by the persons living at home together
with the patient, their guardians or a nurse in an institutionalized facility. The values between rtt=0.68 and rtt=0.89 (all p were
smaller than 0.001) were found, detected in all six dimensions within NOSGER, the values were higher for cognitive dimension
(memory, IADL, ADL) compare to non-cognitive dimensions (mood, social and intrusive behaviour). Retest reliability (stability)
had a bit higher cognitive dimension NOSGER (memory rs=0.91, IADI, rs=0.92, ADL rs=0.88, p smaller 0.001) compare to non-
cognitive dimensions (mood rs=0.85, social behaviour rs=0.87, intrusive behaviour rs=0.84, p smaller 0.001). All of these values
meet the degree rtt bigger or = 0.80, required in a deviation of psychomotoric standards (Whaled et at, 1996).
Brunner and Spiegel (1996) show the NOSGER scale in their work, and also Calabresse, Essner, Forstl (2005) transparently
present the NOSGER scale after 3 and 6 months of a treatment with memantine. The quality of life of the patients with DAT
depends mainly on pharmacotherapeutical possibilities (Gauthier, 2001) but also on associated somatic illnesses, on a progre-
ssion of DAT, intrusive behaviour and ordinary daily activities as well (Walker et al., 1998; Salek et al., 1998).
The quality of life of the patients with DAT living in OPH and NH is affected mostly by us - medical doctors, nurses and ca-
re-givers who have to cope with the biggest burden of care and this care is based on deep moral and ethical principles, or as
Stephen G. Post (2001) says the quality of life is described as a basic principle of love and without it this work is not possible
to carry out.

Conclusion:
The quality of life of the patients with Dementia of Alzheimers type is lower compare to the clients without any psychiatric
burden who live in Old peoples homes and Nursing homes.

106
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2004
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and Abstract Book. Cognitio, Behavior and Social Performence in the Elderby. 2004
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Abstract Book. Cognitio, Behavior and Social Performence in the Elderby. 2004
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Conference of Alzheimers and Parkinsons Disease, Sorrento Italy, 2005
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of quality of life in Alzheimers disease. Quality of Life Researche 10; 2001 443-452
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vskum Alzheimerovej choroby. Bratislava 1998.

107
COMPARISON OF GALANTAMINE AND RIVASTIGMIN EFFECTS -
12-MONTH STUDY

AUTHORS
Dana Ignjatoviov,
MD ,Milan Ignjatovic ,MD

Non Governmental Psychiatric out Department,Jasenova 1, 974 01 Bansk Bystrica, Slovak republic
In our paper we concentrated on a 12-month monitoring of cognitive functions in patients with dementia of Alzheimers
type, using a MMSE test /Mini Mental State Examination/.
In a group A patients were selected who were receiving galantamine 8 mg two times a day /Female N1 = 9/ and an average
age was 75.6 year and an average duration of disease 1.06 year.
In a group B there were 16 pacients selected who received rivistigmine 6 mg two times a day /Female N2= 12/, an average age
was 77.6 and an average duration of disease was 1.4 year.
All the patients met all the ranking criterions for Alzheimers type of dementia.
We recognized that the results of MMSE in the first month of dosage titration were co-equal /20.65 points in a group A and
20.125 points in a group B/; in the 3td month after finishing titration phase in both groups we experienced gentle decrease of
MMSE /16,68 points/ in the group E patients receiving rivastigmine compared to the group A /22,56 pointst patents receiving
galantamine.
In the 12th month of monitoring there was no significant change in MMSE score, and we consider the status in both group
as stabilized.
No patient had the cholinesterase inhibitor discontinued due to any side effects of the drug /Pidrman, 2003; Svestka, 2001;
Cummings, 2003/, however, there were some gastrointestinal difficulties /nausea, lack of appetite, / reported while receiving
rivastigmine, what was solved by an extention of drug titration phase.
In the group A: patients receiving galantamine, there were 8 patients having a caregiver and the same number was reported
in the group B: patients receiving rivastigmine.

Study Goal
To compare galantamine and rivastigmine effects in the treatment of mild to moderately severe Alzheimers type of demen-
tia in a 12-month monitoring, using Mini Mental State Examination /MMSE/ to register possible undesirable drug effects that
could cause the treatment stoppage, disease lasting before diagnosing and a caregiver presence in family /improvement or de-
terioration of patients self-containment/.

Conclusion:
In our study we monitored and compared effects of galantamine and rivastigmine in 32 patents for 12 months. Both drugs
appeared to be effective with a satisfactory degree of safeness and tolerability, though there were some deviations in MMSE
tests during a long-term monitoring pro bono galantamine.

References:
Andreasen NC. Brave New Brain, Conquering Mental Illness in the Era of the Genome, 2001, 345:253-314
Giacobini E: Management of Behavioral Symptoms with Cholinesterase Inhibitors, 12th International Psychogeriatric
Association Congress, Geneva, 2003
Giannakopoulos P, Hof PR, Vallet FG, Giannakopoulos A-S, Charany Y, Bouras C: Quantitative analysis of neuropathologic
changes in the cerebral cortex of centernarians, Prog. Neuro-Psychopharmacol. And Biol. Psychiatr. 1995, Vol.19, pp577-592
Hales RE, Yudifsky SC, Talbott JA: Textbook of Psychiatry, The American Psychiatric Press, 2nd Edition, 1994, 1608:327-347

Summary
In last years Alzheimers dementia have changed from the ignored and hardly eligible part of neurology and psychiatry and
became their key section /Lovestone, 2001/.
In our paper we concentrated on a 12-month monitoring of cognitive functions in patients with dementia of Alzheimers
type, using a MMSE test /Mini Mental State Examination/.
In a group A patients were 16 patients selected who were receiving galantamine 8 mg two times a day /Female N1 = 9/ and
an average age was 75.6 year and an average duration of disease 1.06 year.
In a group B there were 16 patients selected who received rivistigmine 6 mg two times a day /Female N2 = 12/, an average
age was 77.6 and an average duration of disease was 1.4 year.
All the patients met all the ranking criterions for Alzheimers type of dementia.
We recognized that the results of MMSE in the first month of dosage titration were co-equal /20.65 points in a group A and
20.125 points in a group B/; in the 3rd month after finishing titration phase in both groups we experienced gentle decrease of

108
MMSE /16,68 points./ in the group B: patients receiving rivastigmine compared to the group A /22,56 points/: patients receiving
galantamine.
In the 12th month of monitoring there was no significant change in MMSE score, and we consider the status in both group
as stabilized.
No patient had the cholinesterase inhibitor discontinued due to any side effects of the drug /Pidrman, 2003; Svestka, 2001;
Cummings, 2003/, however, there were some gastrointestinal difficulties /nausea, lack of appetite, .../ reported while receiving
rivastigmine, what was solved by an extention of drug titration phase.
In the group A: patients receiving galantamine, there were 8 patients having a caregiver and the same number was reported
in the group B: patients receiving rivastigmine.

Introduction
Dementias are the aging problem. They are like a ticking time bomb /Andreasen, 2001/
Gerontopsychiatry is a part of medicine centered on prevention, diagnostics and treatment of somatic and psychic disor-
ders in elder age. It is the fastest growing area of psychiatry and in 1989 it was officially declared as a subspecialization in the
USA - American Board of Psychiatry and Neurology /ABPN /Kaplan, 1991/.
Geriatric comes from the Greek geras meaning an old age, sear and iatros meaning medicine, clinical, geriatric me-
ans a medical treatment or health in elder age /Kaplan, 1991/.
Pathogenesis of Alzheimers disease is unclear and one of the risk factors of Alzheimers disease outset is age /Giannakopoulos,
1991/, gender, some researches expect higher prevalence of Alzheimer in women, lower education, and also neurotoxicity of
some elements; for example aluminum and iron /Bouras, 1997/.
Another risk factor is a familiar form of Alzheimers disease - changes on chromosome 14 and 21; risky is also middle age of
people with Downs syndrome, which manifests as a progressive dementia.
Another further risk factors are head injuries /Cummings, 20031.
Alzheimers disease is a characteristic example of a cortical dementia /Hales, 2002/.
Gianakopoulos et al. looked for the neuroanatomical correlates of visual agnosia in Alzheimers
The treatment of Alzheimers dementia consists of 4 main parts:
Disease modifying treatment, that leads towards the progression of Alzheimers disease reduction / antioxidants: aipha-to-
coferol and selegilin/.
Cholinesterase inhibitors for improvement, stabilization and reduction of cognitive functions declination /Cummings, 2003;
Pidrman, 2003/.
There are 4 acetylcholinesterase inhibitors known - tacrin /Cognez/ - not used in Slovakia due to its hepathotoxicity, dene-
pezil /Aricept/, galantamine /Reminyl/ and rivastigmine /Exelon/.
While in Slovakia the cholinesterase inhibitors are registered for Alzheimers disease treatment only, according to some
studies they could be used for other dementias with a cholinergic deficit as well - such as the dementia with Lewys bodies,
Parkinsons disease with dementia /Assal, 2003/.
Alzheimers disease with a cerebrovascular illness and a vascular dementia /Cummings, 2003/.
There is a new product on the market, memantin, which is registered in Slovakia from the 1st July, 2004 and does not be-
long to the cholinesterase inhibitors /Pidrman, 2003/.
New possibility of Alzheimers disease treatment is a p-peptid immunization that is still in a research process. Paradoxically,
this treatment is based on the immunization with pathological p-amyloid peptid /A beta/ with the scope to start the immunized
response against the amyloid plaques in the brain /Schenk, 2000/.
Psychotropic agents used for the treatment of behavioral disorder with neuropsychiatric symptoms /Finkel, 1996/, i.e. ris-
peridon, olanzapin, /Cummings, 2003; Katona, 1997; Svestka, 1998/.
Treatment of depression is very important for Alzheimers disease /Verhey, 2000; Bums, 1991/.
Work with the caregivers on their emotional needs saturation and on the alliance improvement of the care optimalisation
for Alzheimer patients /Cummings, 2003/.
Ginkgo Biloba plays an important role in cognitive functions improvement /Patocka, 2001/.
Treatment based on cholinesterase inhibitors could be split up in
stage of titration acute stage, the aim is to achieve a basic therapeutic dosage, with a 4-week basic titration interval; titrati-
on is necessary for both rivastigmine and galantamine.
Second stage of Alzheimers dementia treatment is a long-term /therapeutic stage, achieved therapeutic dosage is applied
for a long period /Pidrman, 2003/.
Galantamine is a cholinesterase inhibitor with a dual effect mechanism, an inhibitor of acetylcholinesterase and alosteric
modulation of nicotine receptors /Lovestone, 2001 1.
Rivastigmine is a combined acetylcholinesterase and butyryleholinesterase inhibitor.
Rivastigmine, unlike donepezil and galantamine, has no significant risk of metabolic interactions.
Possible level oscillation consequent on the short half time is corrected by the pseudoireversible inhibition which takes 10-
12 hours /Pidrman, 2003/.

109
Study Goal
To compare galantamine and rivastigmine effects in the treatment of mild to moderately severe Alzheimers type ofdemen-
tia in a 12-month monitoring, using Mini Mental State Examination /MMSE/ to register possible undesirable drug effects that
could cause the treatment stoppage, disease lasting before diagnosing and a caregiver presence in family /improvement or de-
terioration of patients self-containments/.

Study Design
Galantamine and rivastigmine are registered for the treatment of mild to moderately severe Alzheimers type of dementia
and both have a significant clinical effect as well as a good safety and tolerability attested in many long-term clinical studies
and post-marketing studies.

Group and Methodology

There were 32 patients that fulfill the criterions who were included into a 12-month study. Group A was formed from 16 pa-
tients receiving galantamine 8 mg twice a day and Group B was formed from 16 patients receiving rivastigmine 6 mg twice a
day. We administered MMSE /Mini Mental State Examination/ with patients on the 1st day, after 1st month, after 3rd month, af-
ter 6th month and finally after 12th month of the galantamine or rivastigmine treatment. The overall clinical improvement was
measured by CGI /Clinical Global Impression Test/.

Inclusion criterions
ICD 10 and DSM-IV diagnostic criterions of diagnosis of mild to moderately severe Alzheimers type of dementia
Age above 65
Presence of BPSD /Behavioral and Psychological Symptoms of Dementia/
No previous receiving of galantamine, rivastigmine and donepezil before joining our study

Exclusion criterions
other neurodegenerative diseases
multiinfarction dementia and clinically active cerebrovascular diseases
delirium and other consciousness disturbances
dependences
schizophrenia and schizophrenic disorders
serious somatic diseases of cardiovascular system, kidneys and liver

Results
Our results are summarized in Figure 1 and Figure 2
Figure 1
Patients Profile

Group A /galantamine/ N1=16 B /rivastigmine/ N2=16

Age 75,6 77,6
Gender Female = 9 Female = 12
Duration of disease before 1,06 1,4
diagnosing (in years)
Caregiver presence in family /patients self- 8 8
containment/

Figure 2

Comparison of MMSE /Mini Mental State Examination/ during a 12-month monitoring

MMSE /0/ MMSE /1/ MMSE /3/ MMSE /6/ MMSE /12/
Group /Exami-nation 1st day After 1st month After 3rd month After 6th month After 12th month
Month/
A /gala-ntamine/ N1=16 17,18 20,68 22,56 23,18 23,80
B /rivasti-gmine/ N2=16 18,375 20,125 19,687 20,25 20,56

110
Discussion
In Alzheimers disease there is a severely affected area of central acetylcholinergic system that is important for memory
and a qualitative consciousness level.
For dementia treatment the cognitives are stated, in Slovakia we have three acetylchotinesterase inhibitors available /ri-
vastigmine, donepezil and galantamine/. Rivastigmine inhibits the brain acetylcholinesterases and also butyrylcholinesterases /
Jirak, 2003/.
In our study we concentrated on the comparison of galantamine and rivastigmine effects during a 12- month MMSE test
monitoring. We decided upon the fact that there is a few researches of this type only and more attention was paid to the ob-
servation of donepezil and rivastigmine effects in patients with moderate Alzheimers type of dementia /Wilkinson, 2002/. In
this 12-month study donepezil was tolerated better and both drugs /donepezil and rivastigmine/ showed similar effect on the
cognitive functions improvement.
At 41st Annual Meeting of ACNP /American College of Neuropsychopharmacology/ in Puerto Rico in December 2002 there
were results of a donepezil and galantamine 52-week monitoring presented.
The results were analyzed using MMSE and ADAS-cognition. The analysis showed that the patients receiving galantamine
had better profile of cognitive functions improvement in comparison with those receiving donepezil, while the safeness and
tolerability was similar for both groups /Bullock, 2002/.
On the 6th Congress of European Federation of Neurological Institutes in October 2002, held in Austria, Tryen et al. pre-
sented preliminary analysis of higher galantamine effect on concentration and MMSE in comparison with donepezil during a
52-week monitoring.
McKeith et al. presented a one-year comparative study of galantamine /24 mg/day/ and donepezil /10 mg/day/ and both dru-
gs showed a significant clinical effect and a fair degree of safeness and tolerability /McKleith, 2003/.
Most of the comparative studies we had available were realized with a participation of pharmaceutical companies produ-
cing acetyicholinesterase inhibitors and concerning this aspect it seemed to be necessary to verify the results on our own mo-
nitored patients group.
Our group of patients was quite small /32 patients/ what we consider to be a deficiency of our study, but a long term moni-
toring in ambulatory conditions is rather difficult.
Irrespective of studies supported by pharmaceutical companies we made certain of the good efficiency and tolerability of
both galantamine and rivastigmine.
For none patient we had to discontinue a drug due to side effects, however during rivastigmine receiving we noticed some
gastrointestinal difficulties / nausea, lack of appetite.../, what we solved by extension of drug titration phase.
Patients included into our study fulfill the criterions for an Alzheimers dementia diagnosis and had a comparable basic cha-
racteristic /age, gender, MMSE score of the lst day of monitoring/. After a one-month monitoring there was no difference in
MMSE, in the 3rd month the MMSE score improved with patients receiving galantamine /from 17,18 points to 22,56 points/ and
declined in a group of patients receiving rivastigmine 0,43 point what could be caused by a significant drop of MMSE score in a
patient with aggravated somatic state with dehydration but without hospitalization and retirement from the study.
There were no statistically significant differences between patients receiving galantantine and rivastigmine in neither 6th
nor 12th month score, however more side effects were found in analysis of patient receiving rivastigmine.
Both drugs appeared to be tolerated well and effective during a 12 months long-term monitoring.

Conclusion:
Alzheimers dementia represents a serious medical problem of latest years. It is not only a disease of individuals but it also
affect the whole community /Koukolik, 1999/.
In our study we monitored and compared effects of galantamine and rivastigmine in 32 patients for 12 months. Both drugs
appeared to be effective with a satisfactory degree of safeness and tolerability, though there were some deviations in MMSE
tests during a long-term monitoring pro bono galantamine.

111
POUITIE MOBILNHO TELEFNU AKO POMOCKY PRI PANICKOM
ZCHVATE (USE OF MOBILE TELEPHONE DURING PANIC ATTACK)

AUTHORS
MILAN IGNJATOVIC
DANA IGNJATOVIC
PSYCHIATRIC NON GOVERNMENTAL PSYCHIATRIC OUT CLINIC, CESTA K NEMOCNICI 1,97401
BANSK BYSTRICA, SLOVAK REPUBLIC

SUMMARY
Anxiety disorders together with depressive disorders are one of the most frequently diagnosed disorders. Very often mimicking
somatic disorders, since the intensity of symptoms of cardiovascular, gastrointestinal, respiratory and vegetative systems is not
insignificant and very often the psychiatric consult the very last one requested - frequently leading to demoralization of patients.
In our research we have selected, from the group of patients with anxiety disorder, those meeting the criteria for panic disor-
der and agoraphobia with panic disorder, where panic attack represents acute phase of the disorders which must be addressed..
In the file of first-time examined 72 patients /51 females/, of average age 39 /females 41,5/ we have monitored and recorded
number of all calls by patients to mobile phones of two physicians - psychiatrists, 24 hours a day, for 18 months.
Most patients called in the first month of therapy /26 calls/ and in the second month 20 patients, while in the subsequent
months only 2 patients called - in the third month of therapy.
Patients with other disorders did not call at all.
We have demonstrated that mobile phone can be a good panic tool, which enables remote management of acute anxiety
disorders, without risk of addiction which could result in frequent and pointless phone calls to physicians.

KEY WORDS
Panic attack, panic tool, mobile phone

INTRODUCTION
Agoraphobia with panic disorder is one of the most frequent and relatively well defined anxiety disorders.
Vegetative system manifestations include abdominal and chest discomfort and symptoms related to mental condition /dizzi-
ness, fainting, unrest, vertigo, derealization, depersonalization/ /Smolik, 1996/.
In 1895 first detailed definition of panic attack was coined by Freud as fear neurosis. Later on - during the first world war
Freud says the following about conflict and consciousness: I think that philosophers think too philosophically and take little
notice of primary motives. Therefore I would like to limit and correct the statement: ancient man triumphed over the enemys
dead body without troubling himself about the mystery of life and death. Human thinking was not brought about by any in-
tellectual mystery nor death, but by emotional conflict caused by death of beloved person who at the same time were foreign
and hated. Concsciousness was born of this emotional conflict/Freud, 2003/.
The present article discusses conflicts that may exist in any one of us and especially in our patients with anxiety disorders.
Through development of sciences, biological causes of anxiety disorders were sought in addition to psychological ones. At
the beginning of the last century, an important role in origination of mental disorders was attributed to the axis - sympathetic
system-adrenal glands (core) /Cannon, 1932/.
Selyes arrival on the scientific stage has brought further biological explanations to mental disorders and triggering factors,
using the term stress for the first time. /Selye,1950/.
Stress is defined as general psycho-biological response of an organism to the action of any extrinsic and/or intrinsic stre-
ssor, significantly affecting the homeostasis and causing general adaptive reaction. Individual components of this general adap-
tive reaction affect each other. Their complex interaction is realized through bidirectional processes and mechanisms between
psycho-neural, endocrine and immune systems.
New bio-psycho-social /Engel, 19801, later on holistic models /Goodman, 1991/, multidisciplinary and interdisciplinary approach
to research of stress - psycho-neuro-endocrino-immunology /Ader, 1992/ bring better explanation to complex processes invol-
ving stress and mechanisms through which they are expressed.
Selye divides stress into eustress and distress, discovering that general adaptation syndrome has three successive phases:
alarm phase, resistance phase, and exhaustion phase.
According to our experience, our patients present at our offices with mental difficulties in the second or third phase.
Most of the patients are also defined by learned helplessness /Seligman, 1968/.
Through animal experiments /Henry, 1977/ the authors attempted to find out which system becomes activated in aggressi-
ve and which in submissive subject. They have found that in aggressive subjects the sympathetic- adrenal (adrenal gland core)
axis is activated and in submissive subjects - hypothalarnic-pituitary-adrenocortical axis is activated - with serious consequen-
ces brought about by high cortisol levels.
For our practice it is very important to know how to help people suffering from anxiety disorders, based on bio-psycho-
social model /Engel, 1980/. Therefore we have to know the other /psychosocial/ aspect, in addition to biology and basics of

112
neurophysiology and psycho-pharmacology - i.e. suppression of patient demoralization /which is usually neglected by stan-
dard medicine/, as well as social assistance and support.
Various techniques were developed from psychotherapy through social assistance and support, such as model of calm be-
havior which could be imitated/Bandura, 1977/.
In anxiety disorders, especially agoraphobia with panic attacks, it is necessary to know that that the patients have their pa-
nic partners and panic accessories /Eri, 1991/.
Panic partner is one of the close relatives /spouse, children, parents../ and panic tool can be anything that enables the pati-
ent to better survive the panic attack and elusive agoraphobic behavior.
Eri describes various accessories, including chewing guru, dark sunglasses, walking cane, dark clothing, even close proxi-
mity of ones bed /Eri, 1991/.
Current therapeutic modalities - in addition to modem psycho-pharmacotherapy such as by mirtazapine /Sarchiapone, 2003/
and psychotherapy - individual dynamic short-term psychotherapy, eclectic short-term psychotherapy according to Wolberg
/Flegenheimer, 1982/, -include latest state-of-the art technology, which does not even resemble anything which could be used
as panic tool.
Opposite is the truth - as demonstrated by the present article, where mobile telephone was used as panic tool.

METHOD AND DESCRIPTION OF THE FILE

This is a pilot study.
The file consisted of 72 patients, who met the diagnostic criteria according to ICD-10 and DSM-IV for agoraphobia with pa-
nic disorder F.40.01 and panic disorder /episodic paroxysmal anxiety/ F.41.0.
Each one of the primary patients received a private phone number to mobile phone of their attending physician - psychiatrist.
We have assessed patients age, sex, education, social and financial status, family status API questionnaire was used /acute
panic inventory test/ - not included in the Results.
Over 18 months we assessed the number of phone calls in the first month, second month and during the remaining months
of treatment.
The presentation includes assessment of pharmacotherapy of the patients under survey.

Inclusion criteria:
Age above 18 years
Agoraphobia with panic disorder
Panic disorders
Patients examined at our offices for the first time - since July 1, 2002
Panic tool - patients own mobile phone

Exclusion criteria:
Other psychiatric diagnoses
Co-morbidity with other mental disorders
Patients included in dispensary care

PURPOSE OF THE STUDY:

to monitor the number of phone calls to mobile phone /panic too/ during first, second month of treatment and thereafter
assess social-economical and matrimonial status of the patients
list all medicines used to treat the disorder

ZERO HYPOTHESIS:
Mobile phone cannot be used as panic tool

RESULTS:
The results of our survey failed to confirm the zero hypothesis, mobile phone was shown as suitable and very effective pa-
nic tool used by patients suffering form panic disorder and agoraphobia with panic disorder.
72 patients were included in the survey - according to inclusion criteria for diagnosis of panic disorder and agoraphobia with
panic disorder / males N=51 /average age 39 /females N=41,5 years/ see table 1.
All patients were examined at our offices (2) since July 1, 2002.
Overview of diagnoses - see table 2, whereas anxiety disorders were diagnosed in most patients examined at our offices for
the first time /139 patients/.
Education, social-economical and matrimonial status - see tables 3, 4, and 5.
The more important finding is that mobile phone can be used as a very effective panic tool, as demonstrated by the finding
that highest frequency of calls was during first month - 26 patients /females=14/ and during second month - 20 patients /fema-
les = 11/, then in the following month only two men called in the third month of monitoring. None of the patients with other di-
agnoses called /table 6/.

113
 Medicine used most frequently to treat agoraphobia with panic disorder and panic disorder was paroxetine in average dose
of 20 mg per day - in combination with anti-anxiety drug, sertraline in combination with anti- anxiety drug in 15 patients - dosa-
ge 100 mg per day and citalopram - 20 mg per day - in 12 patients. Overview of drug therapy - see table 7.

DISCUSSION:
There is no life without stress /Kalianin, 2001/.
At the beginning of the last century Walter Cannon /1932/described the fight or ran reaction and found out that this reac-
tion is controlled by sympathetic-adrenal axis /adrenal core/.
Several decades later Hans Selye described stress as being caused by hyper-activity of the hypothalamic- pituitary-adreno-
cortical axis and hypertrophy of adrenal cortex, atrophy of thymus and peptic ulcers as a result of increased cortisol levels in
experimental animal subjects /Selye, 1950/.
Further research. focused on psycho-immunology /Gorman, 1986/, later on psycho-neuro-enclocrino-immunology /Ader, 1992/.
In 1980s great development in medicine and research was brought about by bio-psycho-social model /Engel, 1980/ and ho-
listic approach in 1990s /Goodman., 1991/.
Based on the above theories, a lot of scientists and modem authors attempted to unify in their works the effects of psycho-
social stress factors on bio-psycho-social changes in patients, including structural changes as well as emotional life and beha-
vior of the patients.
Unfortunately in our practice we often meet patients, who are demoralized by exhausting visits of specialists and due to
poor condition of social institutions and lack of funds. Social support and assistance is at the minimum level.
Therefore more emphasis is placed on psychiatric care which is becoming a social buffer (as demonstrated by management
of psychiatric patients by general practitioners).
All psycho-social stressors - beginning from leaving home, completion of school, birth of a child, divorce, through loss of
employment - have negative effects on somatic as well as psychiatric patients.
Selye himself maintained that genetic pre-disposition, stressing factor and personality structure have significant effect on
further development of the disorder.
Two cardiologists - Friedman and Rosenman attempted to define personality type A which is most often affected by cardi-
ovascular disorders /Friedman, 1971/.
Their efforts were not useless, and it helped other researchers to bring system to their work. Similar to situation in cardiology
also in psychiatry we meet with genetic pre-dispositions, psycho-social stress and personality structure with mutual interactions.
Very frequently the psycho-social stressor lies hidden in the patients history - related not only to the events of the previo-
us day or year.
Very often this involves death in the family, followed by fear of death, which is a part of the panic attack, partners infide-
lity followed by failure of adaptive capabilities of the organism. In relation to personality structure, this is dependent or anxiety
personality disorder. An interesting model was proposed by Aron
Antonovsk /Antonovsky, 1995/ and his general resources of endurance, pointing out the fact that great majority of people
will not be affected by a certain type of disorder, focusing on health and not on disease. One of his results is that people who
are resistant to stress, say that it is worth living /Boin , 2001/.
If we take into consideration everything that was written and our practical experience, we can say that most of our patients
is demoralized - which is defined as a complex of destructive postures and emotions, as the condition of mind, accompanied
by anxiety, depressive feelings, loss of sell-confidence, self-respect, feeling of hopelessness, isolation, inability to directly con-
front the new situation /Kalianin, 2001/.
In our practice we meet more and more of such first-time patients. The present article does not attempt to state all reasons
why this is so, however one of the reasons is the lack of time devoted to patients by their physicians.
For the first time I have encountered the term moral at Hopital Universitaire de Geneve, where I worked, and this is one
of the reasons that inspired me to write this article.
Another inspiration came from patients complaining of palpitation, breathing difficulties - attributed to mobile phones in
their left breast pocket.
Obviously we must not forget the effects of modern technology, but similar to computer tomography /CT/, magnetic nucle-
ar resonance /MRI/, spectrophotometry /SPECT/, mobile phones are becoming a part of modern medicine.
Many times they are used to save lives - for example to call for medical assistance after traffic accident, best way to descri-
be this however, is in form of a case report - and we would find that mobile phone can be a good panic tool, enabling expedient
and efficient management of acute anxiety attack, inform the patient and advise on how to manage the panic attack quickly and
efficiently. It is also a method of social support, for which there is a permanent lack of funding in this country.
All parties can save money in the end - including HMOs (medical insurance companies, since such interventions are of great
benefit to patients - they dont have to visit emergency room, they dont have to be hospitalized.
Our pilot study has shown that most patients called the mobile phone numbers of two physicians 24 hours a day for 18
months, most frequently in the first and second month of the treatment.
Frequency after second month was significantly reduced or nil /only 2 patients in the third month of treatment/.
This shows that psychological support and help is effective if its given when patient needs it - in acute phase of panic attack
- leading to significant cost savings in indirect treatment costs..

114
 Within modem short-term dynamic individual psychotherapy Walberg supports the eclectic model, i.e. use hypnosis to get
to deeper unconscious contents, as well as psycho-educational tools - video tapes and audio tapes fore relaxation.
This model is very familiar to us, therefore if we want to really help the patient, 2-3 pills are not enough, we must attempt to
prevent Demoralization of the patient, to develop major effort to ensure social support and assistance to patients.
We opened the article by Freuds words and we will conclude by his words as well: none of our instincts believes in de-
ath. Anxiety caused by fear of death which affects us more frequently than we think is, however, something secondary, usually
arising from feeling of guilt...

CONCLUSION
Mobile phone is a good panic tool, helping to remotely control acute anxiety attack, without risk of addiction which could
be demonstrated by frequent and pointless calling of the physicians - as confirmed by minimum number of phone calls after
second month of survey as well as no calls from other psychiatric patients.

REFERENCES
Ader R/1992/:On the clinical relevance of psychoneuroeimmunology:Clinical immunology and immunopathology, 64, 1, 6
Antonovsk A/1995 a/: The salutogenic Approach to Family System Health: Promise and Danger,Facta Universitatis/Series :
Philosophy and Sociology/,1/2/,89-98
Bandura A/1977/:Self efficacy:Toward a unifying theory of behavioral change. Psychological review, 84, 191-215
Boin AA/20011:Linost i stres, 251:27,30
Cannon W13/1932/:The Wisdom of the Body, 2nd Edition, Norton, New York
Engel GL /1980/:The clinical application of the biopsychosocial model.Am J.Psychiatry,137,535
Eri Lj/1991/:Panina stanja,II.dopunjeno i proireno izdanje,Beograd-Zagreb, 331,12-22,105-156
Freud S/2003/:Podoby psychoanalzy, preklad Krankus M,Boch z nemeckho originlu Sigmund Freud:gesarnmelte
Werke,London, 1940-1952, 119
Flegenheimer WV/1982/: Techniques of Brief psychotherapy,199 :145-154
Friedman M,Rosenman RH/1971/: Type A behavior patterns association with coronary heart disease,Am.Clin.res., 3,300
Goodman A/1991/:Organic unity teory:the mind-body problem revisited,Am J.Psychiatry, 145:5,553-563
Gorman JM/1991/:Psychoimmunology:A Darwinian Approach In psychoimmunology Update
Henry JP/1977/:Stress,Health and the Social Environment, Springer, New York-Heildelberg-Berlin
Kalianin P,Stoinic S,Paleev NR,Slijepevic D/2001/: Stres-zdravlje-bolest,468,130-356,434,437
Kukumberg P,Ul 1/2001/:Panick porucha,212
Sarchiapone M,Amore M,De Risio S,Carli V,Faia V,Poterzio F,Balista C,Camardese G,Ferrari G/2003/:
Mirtazapine in the treatment of panic disorder: an opn-label trial, International Clinical Psychopharmacology, Vol.18, No1
Seligman M/1968/: The alleviation of learned helplessness in the dog.J. Anmorm Soc Psychol.73,256
Selye H/1950/:The Physiology and Pathology of Exposure to Stress,Acta,Montreal

Smolik P/1996/:Duevni a behaviorlni poruchy, Pruvodce klasifikac,Nstin nozologie

Diagnostika,504:243- 299Table l. Overview of patients

Number of patients Average age

Females 51 41.5
Males 21 31.6
Total 72 29.4

Table 2: summery of diagnoses of examined first-time patients

Diagnosis by ICD-1O Number of patients

Z.04 3
F.00-F.09 93 /F.06=58,F.07=5,F.01=8,F.00.1=4,F.00.2=18/
F.10-F.19 35
/F.10=30,F.19=5/
F.20-F.29 12
/F.20=2,F.23=10/

115
 F.30-F.38 36
/F.32=34,F.33=2/
F.40-F.48 139
/F.40.01=29,F.41.0=43,F.41.2=13,F.43=49,F.45=5/
F.50-F.55 12
/F.51=2,F.54=10/
F.60-F.69 4
/F.63=4/
F.70-F.73 8
/F.70=6,F.71=2/

Table 3: Education

Completed level Females Males

Basic (Grammar) school 3 2
Vocational school without diploma 10 2
Vocational school with diploma 19 11
Gymnasium 8 1
University 11 5
Total 51 21

Table 4 social - economical status

Females Males
Student 2 2
Employed 35 16
Unemployed 8 3
Retired-pensioner 6 0
Total 51 21

Table 5: Matrimonial status

Females Males
Single 10 10
Married 27 11
Divorced 8 0
Widowed 5 0
Registered partner 1 0
Total 51 21

Table 6: overview of phone calls to mobile phones

Calls during the first month Calls during second month Calls in the next 16 months
Males 12 9 2*
Females 14 11 0
Total 26 20 2*
*two calls in third month

116
 Table 7 : Overview of used medicines

Therapy Number of patients /72/

No therapy 3
Paroxetine + anxiolytic 29
Citaloprame + anxiolytic 12
Sertraline + anxiolytic 15
Fluvoxamine 3
Fluoxetine 3
Venlafaxine 2
Mirtazapine 3
Other anti-depressant 2

117
TREATMENT OF SOMATOFORM AND PSYCHOSOMATIC DISORDERS AT
OUTPATIENT PSYCHIATRIC CENTER

AUTHORS
Milan Ignjatovic, Dana Ignjatovic
Non Governmental Psychiatric out Department, Bansk Bystrica, Slovak republic

ABSTRACT
Somatoform disorders (SFD) refer to a subgroup of mental disorders where physical symptoms are not conditioned by
physical structural defect. (F45). Patients with somatoform disorders suffer a wide range of physical symptoms e.g. pain, nau-
sea, fatigue, vegetative symptoms and repeatedly insist on physical examinations although previous examinations were negati-
ve (Smolik, 1996). Asthma, dermatitis, eczema, peptic ulcers, mucous colitis and ulcerative colitis belong to a group of psycho-
somatic disorders classified in psychiatry as mental and behavioral factors attributed to other diseases (F54), (Smolik, 1996).
We studied cohort of 46 patients, 21 patients with diagnosis F45 (women N=14 total average age =49 years) and 25 patients
with diagnosis F 54 (women N=17 total average age=53 years). In both groups we observed comorbidity with other mental disor-
ders and made survey of applied theraphy. The most common line of theraphy in patients with somatoform disorders was com-
bination of atypical neurolepticum (sulpirid) + SSRI and anxiolytic agent (8 patients). On the other hand patients with psycho-
somatic disorders were mostly treated with SSRI + anxiolytic agent (15 patients) or with combination of atypical neurolepticum
(sulpirid) + SSRI and anxiolytic agent (8 patients). Patients with somatoform disorders suffered especially from gastrointestinal
tract disturbances i.e. neurosis, dyspepsia and psychogenic aerophagia (F.45.31) 10 patients, cardiovascular disorders (F.45.30)
3 patients. 2 patients had unusual feelings of burning skin (F.45.38). Psychosomatic disorders most frequently occurring were
asthma, migraine and peptic ulcer disease. All patients suffered from the symptoms for the average of 2 or more years.
Key words: Somatoform disorders (F45), mental and behavioral factors attributed to other diseases- psychosomatic disor-
ders (F54), sulpirid.

INTRODUCTION
Patients with somatoform and psychosomatic disorders are the most frequent subjects visiting general practitioners. They
can experience hypertension, asthma, diverse eczemas,
gastrointestinal and urogenital problems. Moreover, physical symptoms can sometimes mask depressive symptoms (for-
merly known as larval or masked depression, today somatoform disorder) or the physical symptoms occur during depressi-
ve episode (somatic syndrome previously referred to as biological, vital, melancholic or endogenomorphous) (Smolik, 1996).
Making the diagnosis we should not forget to omit mood disorders in somatic diseases (malign tumors, drug-induced depre-
ssion, infection, etc.). They are very important in differencial diagnosis. Psychosomatic disorders together with psychosomatic
medicine form interdisciplinary field that comprises collaboration of general practitioners, internists, cardiologists, gastroente-
rologists, surgeons, neurologists and psychiatrists. Sulpirid 2- methoxy benzamid in not only used in the treatment of psycho-
tic and depressive disorders but also in somatoform and psychosomatic disorders. The mechanism of action of sulpirid in afo-
rementioned disorders is not explicitly known. Although dopamine agonists (DA) have antidepressive effect, there are certain
neuroleptics (DA receptor antagonists) that show antidepressive action, also (Schatzberg, Nemeroff, 2001, Janicak 2001). One
of the possible explanations of this paradoxical effect (potency of sulpirid in therapy of depressive and somatoform disorders)
is that neuroleptics, in small doses, can have antidepressive effect acting as DA autoreceptor antagonists thus increasing DA
turnover (Floyd, 1995). Selective blockade of limbic DA receptors with sulpirid is associated with low incidence of neurologic
adverse events. Sulpirid can antagonise DA receptors in blood vessels and gastrointestinal smooth muscles, as well (Turjanski,
1996). Using high doses of sulpirid (400-600mg per day) antipsychotic effect becomes dominant (Janicak, 2001). However,
with low doses of sulpirid (150-300mg per day) we manage psychosomatic, neurotic and depressive disorders (Turjanski, 1996).
Rimon states that sulpirid is efficacious in the treatment of various psychiatric disturbances. Given dose of 100-150mg per day
is applicated in neurotic and depressive disorders. Gastrointestinal symptoms are the most common symptoms in subjects with
somatoform disorders (Fraxinos, 1995). Therefore sulpirid represents new therapeutical modality in the management of those
disorders where visceral hypersensitivity and somatoform component play crucial role (Fraxinos, 1996). Likewise sulpirid co-
mes with new alternative for the treatment of psychosomatic disorders since psychoemotional background is very significant
in the etiopathogenesis of above-mentioned disorders (Lemoine, 1996).
Sulpirid does not decrease the amount of gastric acid in stomach, reduces postprandial serum gastrin levels, stimulates
muconasal defence factors and basal or histamine-stimulated acid production stays unchanged during the course of long-term
theraphy (Lemoine, 1996). Furthermore sulpirid is potent in controlling stress due to its well studied CNS effects (Crismer, 1972)

METHODS
We studied cohort of 46 patients, 21 patients with main diagnosis of somatoform disorder and 25 patients with diagnosis of
psychosoamtic disorder. To interpret comorbidity with other psychiatric diseases and to determine applicated therapy we re-
trospectively analysed patients files without using structural scale.

118
Enrollment criteria:
ICD-10 criteria for somatoform and psychosomatic disorder.
Age 18 to 80 years.
Treated more then 2 years in an outpatient psychiatric center.

Objectives:
To find the most common somatoform and psychosomatic disorders at our outpatient center
To map incidence of comorbitity with other psychical disturbances.
To carry out a survey of the most frequently applied therapeuticals in somatoform and psychosomatic disorders at our out-
patient clinic.

RESULTS
We enrolled a cohort of 46 patients, 21 patients with main diagnosis F45 and 25 patients with diagnosis F54. Average age is
given in Table 1 and Table lb. The most frequent somatoform and psychosomatic disorders were gastrointestinal disturbances
(Tab.2) The comorbidity of somatoform disorders with other mental disorders appeared in the sample of 9 patients, 12 patients
did not show evidence of comorbidity (Tab. 2). The most common psychosomatic disorders were asthma, migraine and pep-
tic ulcer disease. 19 patients had comorbidity with other mental disorders, 6 patients were without comorbidity (Tab. 3). The
most preferred therapy for somatoform disorders was a combination of atypical neurolepticum (sulpirid) + SSRI + anxiolytic
agent (Tab. 4). An overview of SSRI used for this diagnosis is presented in Table 5. Psychosomatic disorders were treated with
SSRI + anxiolytic agent (despite of high comorbidity with anxiety and depressive disorders) or with atypical neurolepticum +
SSRI + anxiolytic agent (Tab 4b).

DISCUSSION
Somatoform disorders present heavy therapeutical problem, not only for general practitioners but also for specialised cli-
nicians during patients hospital stay , because patients symptoms vary widely (Lemoine, 1996). Described disorders cover a
vast amount of psychiatric and other conslutation services (Ignjati). Despite of many repeated examinations, the explanation
that the disorder is not conditioned by structural defect, seems to be unsatisfactory and patients are finally placed in psycha-
tric outpatient centers. Correct diagnosis and treatment prevents ongoing symptoms of chronic illness. Depressive symptoms
may be evident and attributed to somatic or functional symptoms. On the other hand psychatric symptoms can be sometimes
masked by somatic or functional symptoms (Lemoine, 1996). Low doses of sulpirid (100-200mg per day) may be effective in
the treatment of various somatoform disorders. In one double blinded study, Nishida et al. (1974) compared efficiency of sul-
pirid (150-200mg per day) to oxazolam (30-60mg per day) in subjects with somatoform disorders.
At the end of 3-week period patients on sulpirid showed significant improvement compared to oxazolam. Chent and Sttenhouver
(1972) followed 30 patients with symptoms of tachycardia and dyspnoea. Results indicated reduction of symptoms while trea-
ted with low doses of sulpirid. Psychosomatic medicine is an interdisciplinary branch of medicine with typical psychosomatic
disorders e.g. asthma, peptic ulcer disease, migraine and ulcerative colitis (Smolik, 1994). Because of participation of psycho-
emotional component in the etiopathogenesis, sulpirid has a significant role in modification and therapy of psychosomatic dis-
orders (Lemoine, 1996). Migraine is also a very common symptom. Many authors tried to use sulpirid to reduce frequency of
headaches and migraine (Aschoff, 1997, Barr, 1970).
Hakkarainen and Vukari (1973) observed 30 subjects with migraine and 30 subjects with tension headaches, in both groups
symptoms were associated with psychosomatic symptoms. Daily dose of sulpirid was 150mg. Compared to placebo the results
in sulpirid group were much better and lead to alleviation of migraine and tension headaches (Lemoine, 1996). Application of
sulpirid in 20 patients with asthma reduced the rate of attacks. According to Chevalier (1985), although sulpirid has no direct
impact on pathophysiology of asthma, it is effective in the blockade of vicious circle of psychosomatic factors that contribute
to pathophysiology of asthma. Several studies examined potential role of sulpirid (150-200mg per day) in sexual and urological
disturbances (Mazeman,1975). The cons of studies that examined the efficiency of sulpirid in a variety of somatoform and psycho-
somatic disorders are : short period of examination, there are not double blinded, not placebo controlled and they focused on
small number of patients. In spite of this fact, various studies support the application of sulpirid in somatoform and psychoso-
matic disorders treatment. Our survey did not evaluate efficiency of therapy for F45 and F54, but demonstrates the maximum
possible use of combined therapy with atypical neurolepticum (sulpirid) + SSRI + anxiolytic agent is for discussed disorders.
Average dose of sulpirid in our cohort was 100-150mg per day which is comparable to studies mentioned above. Given results
suggest that therapeutical efficiency of sulpirid is indicated by its significant impact upon psycho-emotional component what
might be common for miscellaneous somatoform disorders (Lemoine, 1996). Irritable bowel syndrome is another severe illne-
ss with prevalence of 15-30% in our population. It is characterised by abdominal pain, abdominal discomfort (symptoms for at
least 3 months and several days in a week) and altered bowel habits. There are three major pathophysiological factors for irri-
table bowel disease: abnormal motility, sensitivity and a type of personality (Almy and Tulin, 1947). Those patients suffer from
anxiety, depression and neurotic disturbances (Fraxinos) that corresponds with our data (high comorbidity with anxiety and
depression). While the efficiency of sulpirid in the treatment of irritable bowel disease is under theoretical investigation, sul-
pirid may directly modify physiological processes of patients with peptic ulcer disease. Additional sulpirids quality is the capa-
bility to diminish stress factors. Sulpirid has dual function in reducing stress-induced ulcerations. The local activity normalizes

119
vascularization during pre-ulcerative and ulcerative period and it also indirectly modifies gastric secretion and psychological
activity that contribute to formation of gastric ulcerations (Stein et al., 1994).

CONCLUSION
Somatoform and psychosomatic disorders are very frequent in psychatric outpatient care centers. In differential diagno-
sis it is quite important to exclude depressive episodes since many patients suffering from depression do not present with any
signs of depression. The term somatization applies to somatic symptoms that express emotional discomfort and may lead
to misdiagnosis. A number of depressive subjects with somatic component really have somatic disease, but treatment is often
insufficient. On the other hand many patients with inexplicable diffuse symptoms come to psychiatrist and are diagnosed with
anxiety or depressive disorder (Stahl. ). Correct diagnosis of somatoform and psychosomatic disorder can help with the choice
of pharmacological intervention relevently combined with psychotherapy. One such possibility is represented by combination
of suipirid + SSRI + anxiolytic agent. However this modality needs further clinical studies.

LITERATURE
Table 1 a
Diagnose Number of patients Age
F.45
Male
Female
Total

Table 1 b
Diagnose Number of patients Age
F.54
Male
Female
Total

Table 2
Diagnose Number of patients
F.45 somatoforrn disorder
F.45.2 hypochondric disorder
F.45.30 cardio and KVS system
F.45.31 superior GIT
F.45.32 inferior GIT
F.45.33 respiratory system
F.45.34 urogenital system
F.45.38 other apparatus or system
F.45.4 chronical somatoform painful disorder
Total

Table 3 a
DG Without cormobidity

Table 3 b
DG Without cormobidity

Table 4 a
DG
SSRI
TCA
anxiolytic agent
SSRI + anxiolytic agent
SSRI + typical neurolepticum
Atypical neurolepticum
Biston
Atypical neurolepticum /sulpirid/ + SSRI + anxiolytic agent
Total

Table 4 b
DG

120
 SSRI
SSRI + anxiolytic agent
Atypical neurolepticum /sulpirid/ + SSRI + anxiolytic agent
Other
Total

CASUISTIC
A 24-years old patient was examined at our outpatient psychiatric center in February 2003 for the first time. He had the
first contact with psychiatric center /paediapsychiatric/ at the age of 13 - only psychotherapy ,without psychopharmacotherapy.
At the age of 21 he was treated at outpatient psychiatric center with a diagnose of somatoform disorder, gastric neurosis
F.45.31 with the following advised therapy : maprotilinum 150rng pro die, advised deep psychotherapy, maprotilinum gradually
ex, a change for fluvoxamine.
The patient travelled abroad for 2 months - without difficulties, he has ommited the therapy

RA:
He had been brouht up by his parents until he was 13. Then his father died under unknown circumstances, his family refused
the suspicion of suicide, he has an older sister, ocassional depressive episodes, t.b.: 0, DM: grandfather, ICHS: grandfather, IM:
grandfather, NCMP: probably the great grandparents, ca: great grand father had bowels cancer, alcohol : 0, neuropsychiatric
stress: grand mother was treated at psychiatric center, but he can not name her diagnose, his mother is under monitoring by
outpatient neurology center, because of sclerosis multiplex

OA:
He cameover usual children diseases, more serious diseases in childhood: at the age of 6 Months - coeliakia, operations: APE,
TE, injuries: 0, fractures: 0, unconsciousness : 0, concussion of the brain: caused by downfall, there was only RTG done, allergy
to medicine or to food not declared

SA:
The patient has graduated on secondary industrial school, at this time unemployed, character: rather self-contained, intro-
vert, pesimistic, with schizoid features, he does not go out very often, MS rejected, without seriuos relationship, only tempo-
rary occasional relationships

TO:
He has been suffering from gastric neurosis from the time of his studies on secondary school, It was bearable till the age of
16, it has been getting worse since 2000.
When he was abroad, he had no problems. Last year when he came back, his condition started to get worse, it is critical aga-
in, he tends to vomit, he is loosing his weight, aversion to food, he feels sick all the time, he has sleeeping problems, he thinks
he is not able to go to meet people, only because he feels sick, not because of his anxiety about meeting people

Psychiatric objective:
The patient comes to the psychiatric center alone, neat, he accepts social formalities, hygiene kept, mimicry and gesticula-
tion appropriate, psychomotoric tempo is appropriate.
Consciousness is clear, orientation by person, place, time, situation is right, mood subdepressive, without suicide tenden-
cies, affectivity oscillates, his thoughts are strongly orientated to his somatic qualitative problems of his gatrointestinal tract,
without false contents, perception without qualitative disorders, attention good, IMF appropriate to the age, education, surro-
undings, personality rather introvert, behaviour appropriate.
DG: F.45
F.43.31
Advise:
Paroxetin 20 mg pro die
Clonazepam 2 mg pro die
Sulprid 100 mg pro die

ETIOPATHOGENIC VIEW:
Psychologically the patients self-confidence is lower, psychosocially his gatric problems could indicate the need of fathers love.
Psychoanalytically somatic disorder is an expression of patients anger against unknown person who is responsibile for the
pain caused by fathers death.
Behaviouraly, somatic disorder would express an imitation of his mothers disease (sclerosis multiplex, depressive episodes
) and strict upbringing by one of his parents (mother).

121
BEGINNING AND DEVELOPMENT OF DISEASE
The first symptoms of somatoform disorder occured at the age of 13, in the period of adolenscence, it means before the age
of 30, it was in close relation with violent death of his father, which meant heavy stress for the young man.
Due to the considerable somatic disorder, the patient was repeatedly examined although with negative diagnose. After 5 ye-
ars of lasting physical problems without scructual defect, the patient was advised to see a mental specialist.
His diagnose was somatoform disorder ( gastric neurosis ) with advised therapy.
The patient was working abroad for 2 months, where he did not have any physical difficulties.
After his return, his condition got worse : nauzei, vomiting, aversion to food, loosing weight, wind....
In differencial diagnoses, we have tried to eliminate these somatic diseases collagenoses, S.M.,myastenia gravis, AIDS, hyper-
tyreosis, chronical infection diseases ...), whose physical symptoms can also be temporary and changeable.
We eliminated heavy depressive disorder with somatic symptoms, as there are depressive episodes in the patients family
anamnesis ( mother, sister ).
We eliminated schizophrenia and other psychotic diseases.
Concerning the comorbidity we considered stress and endurance situations.
TH:
Besides psychopharmacotherapy we have advised the patient for psychotherapy as well
(cognito-behavioral psychotherapy)

1.CHECK UP
After a month of treatment , the patient felt better, physical symptoms decreased , at this time the patient is looking for
the job in Slovakia.
IGNJATOVI, B.

122
MODITEN U LEENJU SHIZOFRENIH PSIHOZA
Medu savremenim neurolepticima Moditen zauzima dominantno mjesto u leenju shizofrenih psihoza. Kao snaan antipsi-
hotik brzo reducira shizofreni sadrIaj I stvara brojne ekstrapiramidne simptome. Apliciran u visokim dozama optimalni efekat
ispoljava u dozi od 600 mg sedmino.

UVOD
Medu mnogobrojnim neurolepticima, Moditen nesumnjivo Ina danas zavidno mesto u leenju shizofrenih psihoza. Njegove
glavne karakteristike su : brzo, efikasno i dugotrajno dejstvo. Proizvodi se u tabletama od 1 mg, 2,5 mg, 5 mg, 25 mg I 100 mg,
kao i u injekcijama od 25 mg (Moditen - depo). Polivalentno dejstvo (umirujue, anksiolitiko, sedativno i antipsihotino) svrsta-
va ga u red neuroleptika sa iroklm spektrom dejstva i omoguava mu manevrisanje u pogledu njegove pozologije. To je snaan
neuroleptik, ije antipsihotino dejstvo varira u dozi od 5 do 1800 mg.
Neki autori navode da su najbolji uspeh postigli primenom Moditena u dozi od 150 do 750 mg; drugi navode optimalne doze
od 200 do 400 mg, a kod nekih se kreu ak do 1000. mg. Kao snaan antipsihotik pokazuje vanredne rezultate u kombinaciji sa
sedativnim neurolepticima. Mnogi za neuspeh u leenju navode neadekvatne doze, pa predlau individualno doziranje za svakog
bolesnika ako se eli dobiti optimalno reagovanje.
Zbog njegove dobre podnoijivosti i male toksinosti mnogi preporuuju upotrebu u visokim dozama.

CILJ ISPITIVANJA
U toku ispitivanja pratili smo dejstvo Moditena, njegovo optimalno i minimalno
doiziranje i trajanje medikacije, njegovu toleranciju i efikasnost u leenju shizofrenih psihoza.

NAA ISKUSTVA
U toku desetogodinje primene Moditena u raznovrsnlm oblicima, kombinacijama sa drugim lekovima, kao i raznim dozama,
imali smo mogunosti da pratimo i zabeleimo neke od navedenih prednosti medu drugim neurolepticima. Zbog toga emo u
jednom redosledu nabrajati naa iskustva i nae rezutate ispitivanja.
Naim ispitivanjem obuhvaeno je 47 shizoferenih bolesnika, mukog pola, od 18 do 51 godine starosti. Pre nego to smo
ordinirali lek, obavili smo sve prethodno potrebne radnje predviene za ispitivanje. Kontrolne pslhliatrijske preglede smo vr-
ili na mesec dana.
Ispitivanje je trajalo od 1 do 4 meseca.
Doze niskodoznog Moditena su se kretale od 25 do 75 mg, a visokodoznog od 100 do 800 mg. Tablete smo administrirali
samo ujutro i u podne, a optimalni efekat zabeleili smo na dozi od 600 mg kod 20 bolesnika, na 400 mg kod 4, na 300 mg kod
3, na 100 mg kod 5, na 75 mg kod 2, na 50 mg kod 3 1 na 25 mg kod 2 bolesnika. U toku ispitivanja zapazili smo poboljanje raspo-
loenja, smanjenje anksioznosti, napetosti, a kod nekih poboljanje aktivnosti, interesovanja, voije, autizma, pasivnosti, komuni-
kativnosti, kritinosti, uviavnosti, te usklaivanje ponaanja.
Na kraju leenja sumiranjem rezultata zabeleili smo sledei uspeh:
znatno poboljanje (+ + +) kod 23 bolesnika iii 48,9%
delimino poboljanje (+ + +) kod 16 bolesnika iii 34%
neuspeh ... (0) kod 8 bolesnika iii 17,1%

ukupno 47 100%

SPOREDNI EFEKTI ISPITIVANJA

Nuzpojave smo zabeleili kod 40 bolesnika ili 85,1% a nije ih bilo kod 7 bolesnika lli 14,9%.. Kod bolesnika tretiranih niskodo-
znim Moditenom u tabletama od 25 mg zapazill smo pojavu istih kod svih, a same pojave su bile intenzivne i javljale su se prvog
dana, a kod visokodoznog Moditena od 100 mg kod 7 ih nije bilo, a kod ostalih su se javljale ee na poetku all ih je bilo i docnije.
Poveanje broja leukocita od 8.800 do 17.500 zabeleili smo kod 13 bolesnika ili 27,7%. Broj leukocita se uglavnom povea-
vao kod poveanja doza, a smanjivao kod smanjenja doza.
EEG je blo izmenjen kod 8 bolesnika. Jedina izmena osnovne trase sastajala se u neto iregularnoj osnovnoj aktivnosti, a ret-
ko su zabeleene lake dizritmine pojave uglavnom tokom hiperventilacije, a u jednom sluaju dizritmija je bila granina pre-
ma theta fokusu. Meutim, sve ove diskretne pojave povukle su se posle ukidanja Moditena. Visina doze nije bitno uticala na
pojavu ovih nespecifinih dizritmija.
Ni u jednom sluaju nije dolo do aktivacije specifinosti potencijala.
Osim antiparkinsonika nismo apilcirall drugu dodatnu terapiju. Po zavrenom ispitivanju poste skidanja Moditena pono-
vo smo uvodili prethodnu terapiju, ali u znatno manjoj dozi. 2. Kod 89 shlzofrenih bolesnika, mukog pola, od 21 do 65 godina
starosti, oridnirali smo Moditen u kombi- naciji sa sedativnim neurolepticima uz antiparkinsonik u vremenu od 3 do 7 meseci.
Kombinacije su izgledale ovako: Nozinan
(75 do 600 mg) + Moditen (7,5 do 15 mg) + Artane (6 do 15 mg). Iste takve kombinacije imali smo i sa hlorporomazinom i
Mellerilom.

123
 Na kraju ispitivanja zabeleili smo sledee rezultate:
znatno poboljanje ( + + +) kod 46 bolesnika ili 51,68%
delimino poboljanje(+ +) kod 35 bolesnika ili 39,34%
neuspeh ... (0) kod 8 bolesnika ili 8,98%
Ukupno 89 100%
U toku ispitivanja nisu zabeleeni sporedni efekti ispitivanja. Najbolji uspjeh postignut je u toku leenja u otklanjanju
psihomotornog nemira, anksioznosti, napetosti, straha, autizma, pasivnosti i nezainteresovanosti.
Kod 66 shizofrenih bolesnika, od 21 do 64 godine starosti, ordinirali smo Moditen - depo u ampulama od 25 mg na 25 dana,
u vremenu od 2 do 14 meseci. Od 66 leenih bolesnika 27 nije primalo dodatnu terapiju, a 39 je pored Moditena depo dobi-
jalo i jedan od sedativnih neuroleptika (75 do 300 mg) i Artane (6 do 15 mg), zbog egzacerbacije procesa. Rezultati leenja na
kraju bili su sledei:
Znatno poboljanje (+ + + ) kod 35 bolesnika ili 53%
delimino poboljanje ( + +) kod 14 bolesnika ili 21,3%
neuspeh ... (0) kod 17 bolesnika ili 25,7%
Ukupno 66 100%
Nuzpojava nije bilo kod 37 bolesnka iii 56,06 kod 29 ih je bilo ill 43,94% 4. Kod 20 shlzofrenih bolesnika, mukog pola, od 27
do 46 godina starosti ordinirali smo Moditen u tabletama ad 30 mg dnevno u vremenu od 3 meseca.
Ekstrapiramidalne pojave smo zapazili kod svih u toku prva tri dana, a kod jednog samo 27-og dana i to kod jednih slabije, a
kod drugih jae izraene.
Kod 41 bolesnika, od 25 do 65 godina starosti, mukaraca, obolelih od shizofrenije ordinirali smo Leponex (100 do 600 mg)
i Moditendepo u dozi od 25 mg na 25 dana u vremenskom razmaku od 3 do 7 meseci. Uspeh je bio mnogo bolji nego kod drugih
kombinacija sa Moditenom, a sporedne efekte koje smo zabeleili primmenom samog Moditena nismo ovde zapazili.
Rezultati leenja izgledali su ovako:
znatno poboljanje (+ + + ) kod 32 bolesnika ili 78,0%
delimino poboljanje (+ +) kod 9 bolesnika ili 22,0%
neuspeh (0) kod 0 bolesnika iIi 0,0%
Ukupno 41 100%

ZAKLJUAK
Moditen meu savremenim neurolepticima zauzima dominantno mesto u leenju shizofrenih psihoza. Kao snaan antipsiho-
tik reducira brzo shizofreni sadraj stvara mnogobrojne ekstrapiramidalne pojave. Apliciran u visokim dozama optimalni efekat
ispoljava u najveem broju sluajeva na dozi od 600 mg. Ekstrapiramidalne pojave su ee kod niskodoznog Moditena nego
kod visokodoznog. Otklanjaju se ili spreavaju dodavanjem sedativnih neuroleptika li antiparkisonika. Niske doze Moditena II
Moditenadepo uz sedativne neuroleptike daju bolji efekat u leenju shizofrenih psihoza, a ne daju sporedne efekte. Moditen od
30 mg, kao i niskodozni od 25-75 daju kod svih bolesnikanuzpojave. Moditen-depo uz Leponex daje najbolje rezultate u leenju
bez ekstrapiramidnih pojava zapaenih primenom samog Moditena - depo.

LITERATURA
1) Bohtek, N.: Principi prolongirane psiho farmakoterapije shizofrenih psihoza (znaenje leenja depo neurolepticima) u
Novosti 1 Krka 1972, 85 - 88. 2) Fouks, L.: IVme Congres Mondi al de psychiatrie, Madrid, 1966. Edition squibb et sons. 3) Freeman,
H.: Symposium on long - action phenotiazines. Dublin, 1969. 4) Frank, L.: International Drug Therapy Newsletter. Baltimore,
1970 Vol. 5. N. 4. 5) Flufenazine high dose protocol, E. R. Squibb and Sons LTD. 6) Imlah- N.:Symposium on ong - acting pheno-
tiazines, Dubli,
1969. 7) Korbar, M., Belev, B , Paukovi M : Leenje visokim dozama flufenazin klorida, Neuropsih. 1976, 24, 115 119. 8) Lokar,
L.: Upotreba flutenazin decanoata u socijalnim zavodima. u Novosti 1, Krka, 1972, 95 98. 9) Milovanovi, D : Klinika
psihofarmakologija, Izdanje Lek, Ljubljana, 1972. 10) Medical references, High dosadage moditen (flufenazine) E. R. Squibb
and Sons LTD 11) Nabney, J.: Symposium on long acting phenotiazines. Dublin, 1969. 12) Vitorovi, M.: Naa iskustva na stav u
leenju depo - flufenazinom, u Novosti 1, Krka, 1972, 89-93. 13) Vitorovi M.:
Psihofarmakologija, Zagreb, 1968, 129 132, 294 - 300. 14) Vitorovi, M.: Psihijatrija, lzdanje Lek Ljubljana, 1969, 211 - 217

124
THE MODITEN IN TREATING SCHIZOPHRENIC PSYCHOSES

AUTHOR:

IGNJATOVI, B.
BOIDAR IGNJATOVI, neuropsihijatar
NEUROPSIHIJATRIJSKA BOLNICA DR SLAVOLJUB BAKALOVI VRSAC,
PODVRANSKA, 7

The author expose the results of the treatment of schizophrenic psychoses after ten-year experience in the application of
Moditen in all fashions of it production, as well as in the combination with other neuroleptics. High dosage Moditen administra-
ted in doses from 100 to 800 mg gives an optimal effect at dose of 600 mg in the majority of cases. Low dosage Moditen ad-
ministrated in doses from 25 to 25 to 75 mg provokes many and variable side effects; therefor it should be given together with
antiparkinsonic at the very beginning of healing.
The Moditen insmail doses from 7,5 to 15 mg, applicated with sedative neuroleptics (75 to 600 mg) and antiparkinsonic (6
to 15 mg) yielded good results in healing, but does not provoke extra-pyramidal disturbances.
Moditen-depo, administrated alone or with sedative neuroleptics (75 to 300 mg) and antiparkinsonic (6 to 15 mg) yields good
results in healing and side effects are minimal or none. The Moditen given in tablettes of 30 mg per day provokes in all patients
extra-pyramidal effects, therefor in should be administrated with antiparkinsonics.
Leponex /100 to 600 mg/ being administrated with Moditen-depo /25 mg/ yields the best results in curability, and side effects,
that we meet at Moditen-depo, do not appear.

125
EKSTRAPIRAMIDALNE POJAVE KOD PRIMENE NEUROLEPTIKA NJIHOV
ZNAAJ I LEENJE
Autor iznosi viastita iskustva vezana za pojavu i uklanjanje sporednlh efekata izazvanih aplikacijom flufenazina.
Ekstrapiramidne pojave su ee i intenzivnije kod niskodoznog flufenazina (25 do 75 mg), a slabije i ree kod visokodoznog
flufenazina (100 do 800 mg). Flufenazin u dozi od 30 mg dnevno daje ekstrapiramidne pojave uglavnom u toku prva tri dana (u
100% sluajeva). Esktrapiramidni simptomi se ne javljaju ako se ovaj neurleptik aplikuje zajedno sa sedativnim neurolepticima
i antiparkinsonskim medikamentom.

UVOD
Nesumnjivo je, da neuroleptici zauzimaju dominantnu ulogu u leenju shizofrenih psihoza, pa je zbog toga potrebno pored
poznavanja njihovog psihofarmakolokog dejstva, da se neto vie zna i o ekstrapiramidalnim pojavama koje oni izazivaju. Danas
je, ne samo poznato, ve i dokazano, da se dejstvo neuroleptika odvija uglavnom u nivou retikularne formacije modanog stabla,
bilo direktno ili indirektno, zbog nekih releja sa svim ostalim centralnim nervnim strukturama. Zatim je dokazano, da snani neu-
roleptici, kao to su flufenazini u visokim dozama stimuliu alfa i gama sisteme koji kontroliu aktivnost motornih elija prednjih
rogova i na taj nain prouzrokuju ekstrapiramidalne pojave, a sedativni pak neuroleptici kao to su levomepromazin, hiorproma-
zin i tioridazin, deprimiraju ove sisteme, i tako spreavaju pojavu istih. Odatle i potie podela neuroleptika na snane i sedativne.
Prema tome, ekstrapiramidalne pojave izazvane snanim neurolepticima mogu se predvideti, preduhitriti ili ublaiti dodava-
njem nekog od sedativnih neuroleptika.
Neuroloke manifestacije koje izazivaju neuroleptici, treba shvatiti ozbiljno i uvrstiti in u urgentna stanja koje zahtevaju hit-
nu i adekvatnu medicinsku intervenciju.
U literaturi su opisani mnogi smrtni sluajevi u toku terapije neurolepticima, pa je i zbog toga potrebna predostronost pri
upotrebi istih.
Procenat ekstrapiramidalnih pojava se razlikuje kod mnogih autora, kao i kod primene razliitih neuroleptika. Steck je kod
300 bolesnika, leenlh hiorpromazinom i rezerpinom, uoio pojavu ekstrapiramidalnih manifestacija kod vie od jedne trei-
ne. Rebeillard i saradnici kod 1933 boles- nika leena tioproperazinom nali su ekstrapiramidne manifestacije u 50% sluajeva, a
Maurel i Perrin kod 135 bolesnika u 40% sluajeva. Collard kod haloperldola nalazi ove pojave u 19% sluajeva. Sumirana uesta-
lost nuzpojava kod vlegodinje primene neuroleptika po Milovanoviu je 17%, po Rosieru 51%, po, Aydu 23% I po Paugetu 28%.
Kod udruene primene neuroleptika tioproperazina, flufenazina i tioridazina neki navode 7%..
Nema kriterijuma i pravila pomou kojih bismo mogli da predvidimo pojavu ranih ekstrapiramidalnih manifestacija. Poznato
je da snani neuroleptici izazivaju ove pojave u veem procentu nego drugi neuroleptici. Isto tako se zna da aplicirani bez anti-
parkinsonika daju vei procenat, a u kombinaciji sa sedativnim neurolepticima manji procenat ekstrapiramidainih pojava, da su
te pojave slabijeg intenziteta ili ih nema.
Ekstrapiramidalne pojave najee se javljaju u toku prvih dana aplikacije, a ee su kod mlaih od 25 godina i starijih od
45 godina. Unoenje velikih dozna neuroleptika nema veeg znaaja za uestalost ovih pojava. One su ee kod parenteralne
primene neuroleptika.
U psihijatrljskoj literature postoje dva suprotna stava u pogledu znaaja ovih neurolotih pojava. Prema jednima, one po-
seduju odreden terapeutski efekat, a po drugima su nepoeljne, te ih treba spreavati i otklanjati istovremenom primenom uz
neuroleptike i antiparkinsonike u odgovarajuoj dozi. U prilog drugima ide i otkrie Clozapina, koji ne izaziva ekstrapiramidalne
pojave a irna isti terapijski efekat kao i klasini neuroleptici koji izazivaju ove pojave. Po Milovanoviu (1972) terapijski efekat ne-
uroleptika je jednak, bez obzira da li se primenjuju sami i zajedno sa antiparkinsonicima, all je pojava ekstrapiramidalnih simpto-
ma onemoguena paralelnom primenom istih. Kod bolesnika leenih neurolepticima ekstrapiramidalne pojave su bile registro-
vane u 24% sluajeva, a kod leenih kombinovanom terapijom ih nije bilo.

CILJ
Na zadatak je bio, da na osnovu dugogodinjeg ispitivanja neuroleptika u leenju shizofrenih psihoza, iznesemo naa zapa-
anja i uporedimo nate nalaze sa onim to se do sada zna o neurolepticima i ekstrapiramidalnim pojavama koje oni izazivaju.

NAA ISKUSTVA
1. Flufenazin (Moditen) smo ispitivali kod 47 shizofrenih bolesnika od 18 do 51 godine starosti. Ispitivanje je trajalo od 1 do 4
meseca. Niskodozni flufenazin smo primeniii u dozi od 25 do 75 mg kod 9 bolesnika, a visokodozni flufenazin u dozi od 100 do
800 mg kod 38 bolesnika. Tablete smo ordinirall samo ujutru i u podne, a posmatranje bolesnika vrili u toku celog dana. Nuz
pojave su se javljale najee u toku prepodnevnog rada, ree i popodne, te nam nije bilo teko da ih zapazimo i registrujemo.
Ekstrapiramidalne pojave smo zabeleili kod 40 bolesnika ili 85,1% a nije ih bilo kod 7 ili 14,9. Kod svih 9 bolesni-
ka koji su primali niskodozni flufenazin zapaene su intenzivne ekstrapiramidalne pojave, a kod ostalih 38 bolesnika na visokodo-
znom flufenazinu kod 7 ih nije bilo, i to kod 4 na dozi ad 600 mg i kod 3 na dozi od 100 mg do 300 mg. Kod niskodoznog flufena-
zina E. P. su bile intenzivnije i javljale se odmah na poetku, a kod visokodoznog su se javljale na poetku a i docnije. Primenom
antiparkinsonika u dovoljnoj koliini sve ove pojave su brzo iezavale.
Ove sekundarne pojave mogle su da se jave kod jednog bolesnika po 1,2 ili 3 i to u isto vreme iii u dva razliita vremena, na
poetku, sredini ili kraju.

126
 2. Kod 89 shizofrenih bolesnika, mukaraca, od 21 do 65 godina starosti ordinirali smo Moditen u kombinaciji sa sedativ-
nim neurolepticima uz antiparkinsonik u vremenu od 3 do 7 meseci. Kombinacije su izgledale ovako: Nozinan (75 do 600 mg) +
Modizen (7,5 do 15 mg) + Artane (6 do 15 mg). lste takve kombinacije smo pravill sa hiorpromazinom i tioridazinom.
U toku ispitivanja ekstrapiramidalne pojave se nisu ispoljile ni kod jednog bolesnika, pa ih nismo ni registrovali.
3. Kod 66 shizofrenih bolesnika, mukaraca, od 21 do 64 godine starosti, smo Moditenedepo u ampulama od 25 mg na 25
dana, u vremenu od 2 do 14 meseci.
Od 66 leenlh bolesnika, ekstrapiramidalnih pojava nije bilo kod 37 bolesnika ili 56,06%, a kod 29 smo ih registrovall ili 43,94%.
Nalii smo nesanicu kod 25, akatiziju kod 4, tremor kod 2, rigor kod 2, hipersalivaciju kod 1, I okulogirne krize kod 1 sluaja. Kod
jednog bolesnika javljale su se po 1 ill 2 ill 3 pojave u isto vreme ili u dva vremena. Otklanjali smo lh lako dodavanjem antiparkin-
sonika od 6 do 15 mg.
4, Kod 20 shizofrenih bolesnika, mukog poia, od 27 do 46 godina starosti, ordinirali smo Moditen u tabletama od 30 mg
dnevno, u vremenu od 3 meseca. Ekstrapiramidalne pojave smo registrovali kod svih bolesnika iii 100%. Kod 6 se javilo prvog
dana, kod 7 drugog, kod 6 treeg i kod jednog 27-og dana. Dodavanjem antiparkinsonika od 6 - 15 mg lako smo ih i brzo otklanja-
li. Samo kod jednog bolesnika, gde su ove pojave bile vrlo teke, sa pojavom vie formi paroksizmalnih diskinezija u isto vreme,
morali smo da interveniemo tri sata da bi ih otklonill i bolesnika povratili u prethodno stanje. Kao antidot smo aplicirali 2 amp.
Ponalida, 2 tabl. Artane-a od po 5 mg, detoksikaciju i na kraju iednu ampulu Phenobarbitona od 0,10gr.
5. Kod 41 shizofrenog bolesnika, mukaraca od 25 do 65 godina starosti, ordinirali smo Leponex (100 do 600 mg) i Moditen-
depo u dozi od 25 mg na 25 dana u vremenu od 3 do 7 meseci.
Ekstrapiramidalne pojave koje prate moditen-depo nismo registrovali jer ih nije ni bilo.

ZAKLJUAK
Ekstrapiramidalne pojave su ee i intenzivnije kod niskodoznog flufenazina (25 do 75 mg), a slabije i ree kod visokodo-
znog flufenazina (100 do 800 mg).
Flufenazin uz sedativne neuroleptike i antiparkinsonik ne daje ekstrapiramidalne manifestacije.
Flufenazin-depo (25mg na 25 dana) izaziva ove sporedne pojave u 43,94% sluajeva.
Flufenazin u dozi od 30 mg dnevno daje ekstrapiramidalne pojave uglavnom u toku prva tri dana u 100% sluajeva.
Flufenazin-depo u kombinaciji sa Leponexom ne daje nuzpojave koje se manifestuju aplikacijom samo flufenazina-depo.
Sve navedene pojave lako se otklanjaju uvoenjem antiparkinika od 6 do 15 mg.
Kod teih i komplikovanijih sluajeva dati antiparkinsonik u ampulama i u veim dozama.

LITERATURA
1) Bohaek N.: Principi prolongirane psihofarmakoterapije shizofrenih psihoza, u Novosti 1, Krka, 1972, 85-88. 2) Fouks L.:
1Vme Congrec Mondial de psychiatrie, Madrid, 1966. Edition Squibb et Sons. 3) Flufenazine high dose protocol, E. R., Squibb
and Sons LTD. 4) Korbar M., Belev B., Paukovi M.: Leenje visokim dozama flufenazin klorida, Neuropsih. 1976, 24, 115-119. 5)
Milovanovi D.: Klinika psihofarmakologija, lzdanje Lek, Ljubljana, 1972. 6) Vitorovi M.: Naa iskustva i na stav u leenju de-
po-flufenazinom, u Novosti 1, Krka, 1972, 89-93. 7) Vitorovi, M.: Psihofarmakologija, lzdanje Zagreb, 1968, 129-132, 294-300. 8)
Vitorovi, M.: Psihijatrija, lzdanje Lek, Ljubljana, 1969, 211-217.

EXTRAPYRAMIDAL PHENOMENA IN THE APPLICATION OF

NEUROLEPTICS THEIR IMPORTANCE AND HEALING

IGNJATOVI, B.
The author exposes his experience in connection with the appearance or removing of side effects during ten-year admini-
stration of the fluphenazine. So high dosage of fluphenazine in doses from 100 to 800 mg in 40 patients provoked extrapyrar-
nidal phenomena or 85,1 %, in 7 patients these phenomena did not appear or 14,9 %. Low dosage fluphenazine, from the other
side, administrated in doses from 25 to 75 mg provoke these phenomena 100 %.
Fluphenazine in the dose of 7,5 to 15 mg in combination with sedative neuroleptic (75 to 600 mg) and antiparkinsonic (6 to
15 mg) does not give extra-pyramidal distrubances.
Moditen-depo applicated in injections by 25 mg for 25 days provoked extra-pyramidal disturbances in 56,06 %.
During the administration of fluphenazine in tablette of 30 mg daily, we noted extra-pyramidal disturbances 100%.
By the application of Leponex (100 to 600 mg) together with Moditen-depo (25 mg) we did not find the extra-pyramidal
symptoms that appear in the application moditen- depo only.
Low dosage fluphenazines, consequently, in doses from 30 to 75 mg seem to give 100 % extra-pyramidal phenomena, the-
refor they should be given from the very beginning with antiparkinsonics or sedative neuroieptics preventing on that wy the
undesirable action.
Boidar Ignjatovi, neuropsihijatar
Neuropsihijatrijska bolnica Dr. Stavoijub Bakalovi Vrac, Podvranska, 7

127
PENFLURIDOL U LEENJU HRONINIH SHIZOFRENIH PSIHOZA
Penfluridolom je tretirano 26 hroninih shizofrenika; sedmina doza neuroleptika bila je izmeu 20 i 60 mg. Ispitivanje je
trajalo od 3 do 14 meseci.
Autori referiu o rezultatlma koji su postignuti aplikacijom Penfluridola.

UVOD
Penfluridol /R 16 341, zatieno ime Semap/ spada u neuroleptike novijeg datuma. Njegova neuroleptika aktivnost i slaba
toksinost dokazani su serijom eksperimenata vrenim na mievima, pacovima, psima, zeevima i zamorcima. Njegove najslablje
efektivne doze su 8 do 16 puta manje od doza hlorprornazina, a pribline dozama haloperldola i pimozida.
Veliki broj klinikih ispitivanja ukazuje na povoljno dejstvo Penfluridola u produenom tretmanu kod hroninih psihoza, gde
su dominirall deficitarni simptomi /autizam, apatija, pasivnost, snienje afektiviteta, dezinteresovanost/, kao i ispoljeni simptomi
sumanutosti i halucinacije. Meutim, manje je bio efikasan kod ispoljenog psihomotornog nemira i agitacije, te su uz Penfluridol
bili dodavani i sedativni neuroleptici. Procenat poboljanja u tretmanu Penfluridolom, prema nekim kliniarima, kretao se od
30 do 70%, a negde ak i do 85%.
Po miljenju mnogih kliniara, Penfluridol je oralni neuroleptik, koji ispoljava snaan antipsihotini efekat, all skoro nikakvo
sedativno i hipnotiko dejstvo, sa pojavom minimainih sporednih efekata i prolongiranim delovanjem od 7 dana, te je pogodan
za primenu u leenju i odravanju hroninih psihotinih bolesnika iz shizofrene grupe, kojima je potreban produen tretman.
Najbolji terapeutski efekti se navode primenom pojedinanih sedminih doza od 40 do 60 mg, a lek se nalazi u prometu od
20mg u tabletama.

CILJ ISPITIVANJA
U toku ispitivanja pratill smo dejstvo Penfluridola, njegovo optimalno doziranje i trajanje madikacije, njegovu toleranciju.

NAA ISKUSTVA
Naim ispitivanjem obuhvaeno je 26 hroninih shizofrenih bolesnika, mukog pola, od 30 do 54 godine starosti, sa traja-
njem bolesti od 3 do 25 godina. Po dijagnostikoi strukturi zastupljenost je bila sledea: Sch.simplex /295.0/ 3 bolesnika ili 11,54%,
Hebephrenia /295.1/ 9 bolesnika ili 34,62%, Catatonia /295,2/ 2 bolesnika ili 7,69%, Sch.paranoldes /295,3/ 12 bolesnika ili 46,15%.
Neuroloki i somatski nalazi pri pregiedu su bili uredni. Pre nego to smo ordinirali Penfluridol obustavili smo prethodnu te-
rapiju samo za jedan dan i u toku tog dana napravili potrebne laboratorijske analize i kontrolne psihijatrijske preglede.
Sledee kontrolne psihijatrijske preglede kao i laboratorijske analize vrili smo na kraju prvog, drugog i treeg meseca i za-
jedno sa prethodnim uneli u odgovarajue test liste. Kod bolesnika koji su leeni due od 3 meseca kontrolne psihijatrijske pre-
glede smo vrili i delje na mesec dana.
Ispitivanje je trajalo od 3 do 14 meseci. Doze Penfluridola su se kretale od 20 do 60 mg /1 do 3 Tabl./ svakog sedmog dana.

REZULTATI LEENJA
Evaluaciju terapeutskog efekta vrili smo pre poetka leenja, a zatim u razmacima od po 4 nedelje, pomou kratke psihi-
jatrijske ocenske lestvice s 19 osobina i 4 stepena ocene simptoma: 0 odsutan, 1 = blago izraen, 2 = umeren, 3 = jako izraen.
Na kraju leenja sumiranjem rezultata zabeleili smo sledei uspeh:
znatno poboljanje kod 11 bolesnika ili 42,30%
delimiano poboljanje kod 10 bolesnika ill 38,46%
neuspeh kod 5 bolesnika ili 19,24%
Kod svih bolesnika leenje smo poeli u bolnici, all smo posle otputanja nekih bolesnika nastaviii tretman i daije primenom
Penfluridola, uz uobiajene mesene kontrole. U toku ispitivanja, kod 3 pacijenta je dolo do pogoranja bolesti sa pojavom psi-
homotomog nemira, agitiranosti, napetosti i sumnjiavosti, te smo bili prinueni da uz Penfluridol ordiniramo i jedan od seda-
tivnih neuroleptika /Leponex/ i tako otklonimo postojei psihopatoloki sadraj. U toku leenja zapazili smo najbolje poboljanje
u voljnoafektivnoj sferi, sa izraenom stimulacijom afektiviteta, a zatim vidno poboljanje interesovanja, aktivnosti, komunika-
tivnosti, inicijative, ponaanja i spoljanjeg izgleda.

SPOREDNI EFEKTI ISPITIVANJA

Sporedni efektiiIspitivanja bili su zapaeni u sledeem redosledu: nesanica kod 9, umor kod 6, miini nemir kod 6, hipno-
sedacija kod 4, nedostatak izraajnosti kod 3, akatizija kod 3, miini tremor kod 2, akazizija i tazikinetija kod 1, okulogirne krize
kod 1, rigidnost miia kod 1, protruzija jezika kod 1,i parkinsonizam kod 1 bolesnika. Sve ove gore navedene nuzpojave javljale
su se najee na poetku leenja i nisu zavisile od doze leka. Nesanicu smo otklanjali uvoenjem Mogadona, a ostale nuzpoja-
ve ordiniranjem antiparkinsonika od 6 do 15 mg dnevno. Efekat je bio brz, a sve pojave blage. Interesantno je napomenuti, da je
jedan bolesnik, za celo vreme dok je bio na Penfluridolu, to jest za vreme od 14 meseci, dok je primao po 20 mg sedmino, bio
u dobroj remisiji, a nuzpojave nisu bile zabeleene.

128
ZAKLJUAK
Penfluridol /R 16 341,Semap/ je neuroleptik sa protrahiranim dejstvom ali bez hipnosedativnog dejstva. U toku ispitivanja za-
pazili smo njegovu terapeutsku eflkasnost kod hroninih shizofrenlh psihoza dueg trajanja. Njegovo stimulativno i antiautisti-
ko delovanje, kao i oralna primena, daju mu prednost meu psihofarmacima, a snano antipsihotino dejstvo ga ubraja u red
savremenih neuroleptika.

LITERATURA
1) Bobon J., Melon J Mormont., C., Dufrasne M., Pinchard A., Neuroleptique longue duree d action. III: Etude pilote du
penfluridol. Acta Neurolog. Belg.70,523,1970. 2) Janssen Pharmaceutica: Basic medical information on Penfluridol Research
Laboratories, 1973. 3) Mormont Ch.: Neuroleptiques longue duree d action. III. Etude pilote du penfluridol /R 16 341/: dones
psychomtriques, Acta Psychiat. Belg. 72, 595, 1972. 4)Roelofs G.: Penfluridol /R 16 341/ as a maintenance therapy in chronic
psychotic patients: a double-blind clinical evaluation. Acta psychiat. scand. 1974, 50, 219-224.

SUMMARY

PENFLURIDOL IN TREATING THE SCHIZOPHRENIC CHRONIC

PSYCHOSES
Penfluridol /R 16 341/ was administrated by us in 26 chronic schizophrenic patients of male sex, 30 to 54 years old, with case
history from 3 to 25 years.
The investigation lasted from 3 to 14 months and doses varied from 20 to 60 mg /or 1 to 3 tabl./ per week.
In the course of this investigation we reached the following results:
notable amelioration / + + + / in 11 patients or 42,30%
partial amelioration / + + / in 10 patients or 38,46%
unsuccess /0/ in 5 patients or 19,24%
Total 26 100%
Side-effects were mild and negligible and we removed them by the administration an oral antiparkinsonian agent from 6
to 15 mg.
Penfluridol, as a potent antipsychotic with prolonged duration of action and easy oral administration, has found its place
among the modern neuroleptics in treating the schizophrenic chronic psychoses.
Boidar Igniatovi, neuropsihijatar
Nouropalhijatrijska bolnica Dr. Slavoijub Bakalovi Vrac, Podvranska, 7

IGNJATOVI, B.

129
ZNAAJ VISOKIH I NISKIH DOZA NEUROLEPTIKA U LEENJU
SHIZOFRENIH PSIHOZA
Autor opisuje iskustva pojedinih autora, kao vlastito iskustvo steeno primjenom visokih, srednjlh i niskih doza neuroleptika.

UVOD
Danas je poznato, da neuroleptici kao psihotropne supstancije zauzimaju dominantno mesto meu savremenim psihofar-
macima. Njihova uloga i znaaj u leenju shizofrenlh psihoza imaju prioritet u terapijskom pristupu. Iskustva u primeni istih su
mnogobrojna i raznovrsna, a postignuti rezultati veoma povoljni u otklanjanju psihopatoloke simptomatologije. Meutim, po-
stoje vidne razlike u doziranju. Dok jedni preporuuju niske i srednje doze drugi su za primenu visokih doza neuroleptika.
Trea grupa kliniara daje prednost kombinaciji dva ili vie neuroleptika. Sigurno je, da sva tri predloga imaju svoje opravda-
nje, te bi na cilj bio da na osnovu naih ispitivanja i postignutih rezultata doprinesemo pravilnom usmeravanju primene neuro-
leptika, kao i upoznavanju sa njihovim pozitivnim i negativnim osobinama u okviru predlagane pozologije.
Nesumnjivo je, da razliite doze neuroleptika ispoijavaju i razliita dejstva. Meutim, i jedan isti neuroleptik, moe da ima ra-
zliite efekte na postojei shizofreni sadraj, a sve to zavisno od doze, tolerancije i evolucije postojee psihoze.
Poznato je, da neuroleptici u malim dozama ispoljavaju samo psiholeptiko dejstvo, a u veim i hipnotiko. Isto tako se zna,
da sedativni neuroleptici u veim dozama imaju antipsihotino dejstvo, a antipsihotini u veim dozama i sedativno dejstvo.
Znai da svi neuroleptici istovremeno poseduju i sedativno i antipsihotino dejstvo, zavisno od doze koja bude primenjena u da-
tom momentu. Tako se namee pravilo, da bi za postizanje odgovarajueg efekta bilo potrebno primeniti i odgovarajuu dozu.
Levomepromazin (Nozinan) u manjim dozama ima umirujue dejstvo i pojaava san, u srednjim je odlian anksiolitik, a u ve-
im pored sedativnog ispoljava i antipsihotino dejstvo.
Radi boije i to preglednije ilustracije pozologije i efekta neuroleptika, kao najbolji primer moe da nam poslui flufenazin
(Moditen) koji ispoljava polivalentno dejstvo: umirujue u malim dozama od 0,5 do 5 mg; anksiolitiko od 100 do 200 mg; seda-
tivno od 100 do 1500 mg i antipsihotino od 5 do 1800 mg dnevno. Dalje se zna, da flufenazin u dozi od 0,25 do 2 mg ima umi-
rujue dejstvo kod neuroze, a u srednjim dozama od 10 do 300 mg anksiolitiko i antidepresivno, Kod manijakodepresivnih psi-
hoza, u maninoj fazi, vee doze flufenazina mogu izazvati depresivno raspoloenje.
Doziranje flufenazina je strogo individualno, pa je potrebno istraivati optimalnu pozologiju a ne mlnimalnu kao to se to
radi sa drugim neurolepticima.
Ako je doziranje neuroleptika nedovoljno, bolesnici se ale na brzo zamaranje, depresivne tendencije, afektivnu tupost, aste-
nine smetnje, te postaju pasivni, anksiozni, mrgodni i mrzovoljni, a prethodno postojei pslhopatoloki sadraj poinje da eg-
zacerbira pa bolesnik izgleda kao da se mui, kao da mu neto nedostaje. Svi ovi gore navedeni simptomi nestaju kad se doze
neuroleptika poveaju.
Kao efikasne doze flufenazina neki preporuuju 200 do 400 mg, a kod nekih se one kreu do 1000 mg.
Kod predoziranja, bolesnik je obino usporen, inhibiran, pasivan, vie ili manje nesvestan svojih poremeaja, somnolentan.
lz tih razioga se ne ali na svoje tegobe ve ih podnosi pasivno i ravnoduno. Po pravilu, njegova okolina upozorava na njegovu
apatiju, usporenost i somnolenciju. Predoziranje moe takoe odravati ili prouzrokovati pslhotine poremeaje, aktivirati ili
pojaati halucinacije. Sve ove pojave nestaju nakon naglog smanjenja doze datog neuroleptika.
Doziranje flufenazina je strogo individualno i to kako premo svakom bolesniku, tako i premo involutivnom vremenu bolesti
svake osobe, a kree se u granicama od 2 do 1800 mg. Taj njegov raspon u efektivnom doziranju, zahteva od terapeuta stalan i
neprekidan nadzor, kao i najpaljiviju budnost. Uzrok mnogih smrtnih ishoda, koji se navode u literaturi, moda lei ba u odsu-
stvu ovih mera predostronosti a ne u visokoj dozi neuroleptika.
Gayral I Lambert (1966) su na 142 bolesnika ispitivall flufenazin u dozama izmeu 100 do 1000 mg za vreme od tri godine. Lek
su primenjivali uglavnom kod shizofrenih bolesnika i zabeleili znaajno poboljanje autizma, inertnostl i apragmatizma. Oni su
vrlo esto uz flufenazin ordinirali i visoke doze sedativnih neuroleptika od 100 do 500 mg radi postizanja boljeg sedativnog efekta.
Korbar I sar. (1976) navode da su najbolje rezultate postigli primenom visokih doze flufenazina od 600 mg.
Neki autorl navode optimalne doze od 150 do 7500 mg. Dalje se opisuje dobra podnoljivost flufenazina u dozi od 50 do 500
mg bez znaajnih kardiovaskularnih promena.
Mi smo na naem materijalu, kod ispitivanja flufenazina u dozi od 100 do 800 mg, postigli optimalan uspeh u leenju shizo-
frenih psihoza na dozi od 600 mg u najveem broju sluajeva. Meutim, osim ispoljenih sporednih etekata kod nekih bolesnika,
drugih nepoeljnih sekundarnih pojava nismo imali.
lz literature su poznata i dva smrtna sluaja (Henry, 1971) kod aplikacije Moditena-depo.
Vitorovi (1967) navodi 28 smrtnih sluajeva kao posledice neuroleptika kod starijih bolesnika, zatim leenih od aterosklero-
ze, sranih oboljenja i kod osoba sklonih ortostatskom kolapsu. Isti autor navodi i komplikaclje pri upotrebi niksih ambulantnih
doza neuroleptika pa zbog toga preporuuje obazrivost kod starijih, ateroskleroze, hipertoniara, vegetativno labilnih i tamo
gde je CNS lediran pre terapije.

NAA ISKUSTVA
U toku desetogodinjeg iskustva imali smo mogunosti da primenjujemo flufenazin u svim oblicima prolzvodnje: tabletama
od 1 mg, 2,5 mg, 5 mg, 25 mg, 100 mg i ampulama u depo obliku od 25 mg. Polivalentno dejstvo kao i razliit uspeh u leenju shi-
zofrenih psihoza zavisio je uglavnom od doze i evolucije bolesti.

130
 Kod 47 shizofrenih bolesnika, mukaraca, od 18 do 51 godine starosti primenjivali smo niskodozni flufenazin (25 do 75 mg) i
visokodozni flufenazin (100 do 800 mg) dnevno u vremenu od 1 do 4 meseca.
Kod 11 bolesnika smo primenili niskodozni flufenazin, a kod 38 visokodozni.
Optimalni efekat smo zabeleili kod 20 bolesnika na dozi od 600 mg, kod 4 na 400 mg, kod 3 na 300 mg, kod 5 na 100 mg,
kod 2 na 75 mg, kod 3 na 50 mg i kod 2 na 25 mg.
lz ovoga se vidi, da smo najbolji uspeh, kod najveeg broja sluajeva, postigli na dozi od 600 mg, all se vidi i to da optimalne
doze nisu iste kod svlh, te ih treba traiti i na njima se due zadeavati. Jedna ista doza kod jednog bolesnika moe da bude op-
timalna, kod drugog nedovoljna, a kod treeg da ukazuje na predoziranost i nepodnoljivost. Na kraju smo zabeleili sledee re-
zultate: znatno poboljanje kod 23 bolesnika ili 48,9% dellmino poboljanje kod 16 ili 34 % i neuspeh kod 8 ili 17,1%. Nuzpojave
smo zabeleili kod 40 sluajeva ili 85,1%.
Kod 89 shizofrenih bolesnika, mukaraca, od 21 do 65 godina starosti, primenjivali smo flufenazin (7,5 do 15 mg) uz jedan od
sedativnih neuroleptika (75 do 600 mg) i antoparkinsonik (6 do 15 mg) u vremenu od 3 do 7 meseci. Na kraju smo zabeleili sle-
dee rezultate: znatno poboljanje kod 46 ili 51,68%, delimino poboljanje kod 35 ili 39,34% i neuspeh kod 8 ili 8,98%. U toku
ispitivanja nuzpojave nismo zabeleili. Bolji uspeh je zapaen primenom ove kombinovane terapije.
Kod 66 shizofrenlh bolesnika, mukog pola, od 21 do 64 godine starosti, primenili smo Moditen-depo od 25 mg na 25 dana, u
vremenu od 2 do 14 meseci i to kod 27 samo Moditen-depo a kod 39 pored njega dodali smo i 1 sedativnl neuroleptik (75 do 300
mg) i 1 antiparkinsonik (6 do 15 mg). Rezultati su bili sledei: znatno poboljanje kod 35 ili 53%, delimino poboljanje kod 14 ili
21,3% i neuspeh kod 17 ili 25,7%. Upadijivo je da su rezultati priblino kao kod primene visokodoznog i niskodoznog flufenazina.
Nuzpojave su bile ispoljene kod 29 sluajeva ili 43,94%.
Kod 20 shizofrenlh bolesnika, mukog pola, kod 27 do 46 godina starosti, ordinirali smo flufenazin u dozi od 30 mg dnev-
no. U toku leenja morali smo da dodajemo kod nekih i po jedan od sedativnih neuroleptika (75 do 300 mg) da bi postigli bolji
efekat u otklanjanju psihopatolokog sadraja, kao i jedan antiparkinsonik (6-15 mg) radi otklanjanja ekstrapiramidalnih pojava
kojih je bilo 100%.

ZAKLJUAK
Dejstvo neuroleptlka, prikazano na flufenazinu, moe da bude polivalentno, to jest u razliitim dozama razliito. Efekat dej-
stva zavisi od doze, tolerancije i evolucije psihoze.
Optimalni efekat se postie kod flufenazina u najveem broju sluajeva na dozi od 600 mg, kao i na niim dozama ali uz da-
vanje jednog od sedativnih neuroleptika.
Doze od 30 mg su kod pojedinlh bolesnika nedovoljne za otklanjanje postojeeg shizofrenog sadraja, te je potrebno admi-
nistrirati i po jedan sedativnl neuroleptik.
Nuzpojave su ee kod doze od 30 do 75 mg nego kod doza od 100 do 800 mg, te za boiji uspeh dodavati i antiparkinsonik.

LITERATURA
1 ) Males medico-psychologiques, 1965, 5, 821-824. 2) Congres international de neuropsychopharmacologie, Washington, 1966,
3) Fouks, L.: IVme Congres Modial de psychiatrie, Madrid, 1966. 4) Flufenazine high dose protocol, E.R. Squibb and Sons LTD. 5)
Korbar, M. , Belev, B., Paukovi, M.: Leenje visokim dozama flufenazin klorida, Neuropsihijatrija, lzdanje Zagreb, 1976, 24, 115-
119. 6) La Presse Medicale, 1971, 51 1757. 7) Milovanovi, D.: Klinika psihofarrnakologija, Izdanje Lek, Ljubljanja, 1972. 8) Medical
references, High dosage moditen/flufenazine/ E.R. Squibb and Sons LTD. 9) Petrovi, D., Sedmak, T.: Psihofarmakoterapija dugo
leenih psihoza shizofrenog tipa, u Anali zavoda za mentalno zdravlje, Beograd, 1974. 10) Vitorovi, M.: Psihofarmakologija, lz-
danje Zagreb, 1968, 129-132, 294-300. 11) Vitorovi, M.: Psihijatrija, Izdanje Lek, Ljubljana, 1969, 211-217.

THE IMPORTANCE OF HIGH AND LOW DOSES OF NEUROLEPTICS IN

TREATMENT SCHIZOPHRENIC PSYCHOSES

IGNJATOVI, B.
The author describes the experience of the other reseachers as well as his own in the appliance of high, midle and low do-
ses of neuroleptics, on the bases of the administration of fluphenazine (Moditen) being alone and in combination with sedati-
ve neuroleptics.
Polyvalent action of Moditen depends on the doses, but the optimal effect was reached at dose of 600 mg in the bigest
number of schizophrenic patients; some workers give doses from 100 to 750 mg.
By the application of low doses of fluphenazine, as well as in the case of unsufficient dosage - better results in the reduction
of schizophrenic content were noted by the increase of the doses of moditen or by the addition of the sedative neuroleptics.
By product symptoms appeared sooner at the low-dose moditen than at the high-dose one. These symptome were remo-
ved by the addition of anti-parkinsonics.
Boidar Igniatovi, neuropsihijatar
Neuropsihijatrijska bolnica Dr Slavoljub Bakalovi

131
RACIONALNA UPOTREBA PSIHOFARMAKA
(Izvodi iz predavanja odranih u okviru Sedmog seminara za struno poslediplomsko usavravanje lekara dana 7. maja 1977.
godine u Vrcu)

Predavai:
Prof. Dr Dimitrije Milovanovi, Neuropsihijatrijska klinika Medicinskog fakulteta, Beograd;
Prof. Dr Vladislav Varagi, Farmakoloki institut Medicinskog fakulteta, Beograd;
Prof. Dr Stojan Vukovi, Institut za neuropsihijatriju i mentalno zdravlje, Medicinski fakultet, Novi Sad;
Dr Boidar ignjatovi, neuropsihijatar, Neuropsihijatrijska bolnica, Vrsac, u koautorstvu s dr Brankom Vukoviem, dr Draganom
Jevdiem, dr Dragoljubom Jovanoviem i dr Svetozarom Bokorovom, neuropsihijatrima Neuropsihijatrijske bolnice, Vrsac.
Psihofarmaka su za nepune tri decenije svoga postojanja zauzela vrsto mesto u savremenoj medicini. Ova grupa lekova izla-
zi daleko izvan podruja rada neuropsihijatra. Pored upotrebe od strane specijalista svih grana klinike medicine, ova sredstav
ulaze u svakodnevni terapijski arsenal lekara opte prakse. Prema nedavno sprovedenim istraivanjima Zavoda za farmakologiju
i toksikologiju medicinskog fakulteta u Novom Sadu, u kojima se korienje lekova izrazilo kroz broj doza izdatih za pojedine far-
makoterapijske skupine lekova, zastupljenost psihofarmaka ini ak 11% svih propisanih doza u ambulatnim uslovima (receptura
SIZ Novi Sad) i 17% od svih primenjenih doza na klinikama Medicinskog fakulteta u Novom sadu. Slini podaci kao na klinikama
Medicinskog fakulteta u Novom Sadu su i podaci dobijeni istom metodologijom u Medicinskom centru Dr Radivoj Simonovi
u Somboru. Pri tome je naeno da sve klinike i sva odeljenja ove dve ustanove koriste psihofarmaka u znaajnoj meri. Ovi poda-
ci stoga jasno govore o potrebi stalne edukacije lekara o racionalnoj upotrebi ove relativno nove skupine lekova.
Medicinski pregled je u svome dvo-broju 9/10 (volumen 30), 1977, str. 509-512 ve objavio tekst profesora Stojana Vukovia
pos naslovom O psihijatrijskoj dijagnozi danas. Taj tekst sadri deo materije koju je prof.Vukovi izneo, pa se italac upuu-
je tamo. U istom broju ovoga asopisa (str.513-515) objavljen je lanak doc.dr Milana Stanulovia, doc.dr Nile Kapor-Stanulovi
i doc.dr Branka Bania pod naslovom Problemi u klinikoj oceni efekata psihofarmaka, i na koji takoe upuujemo zaintere-
sovanog itaoca.

PREGLED KLINIKE UPOTREBE SAVREMENIH PSIHOFARMAKA

D. Milovanovi
Dosadanja iskustva sa psihotropnim supstancama opravdala su njihovu primenu ne samo u psihijatriji, ve i u nizu
drugih medicinskih disciplina. Za etvrt veka svog postojanja i razvitka ova nova oblast, interdisciplinarno postavljena psiho-
farmakoterapija sakupila je veliki broj novih saznanja, uoila aktuelne probleme i odredila puteve daljih istraivanja. Niz nere-
enih pitanja ipak ne umanjuje svu ekstenzivnu i intenzivnu racionalnu upotrebu razliitih vrsta psihofarmakolokih sredstava.
U svetlu klinikeprakse pitanje njihovog klasifikovanja nije do kraja usaglaeno. Ovome ne protivureu injenica da su ovde mo-
gui razliiti pristupi, kao: biohemijski, farmakoloki i drugi, ali se u najveem broju sluajeva ima u vidu njihovo delovanje na
ponaanje oveka i ovaj aspekt postaje vodei prilikom izrade svake vrste klasifikacija. U tom smislu psihofarmaci se dele u tri
velike grupe: psiholeptike, psihoanaleptike i psihodizleptike.
Najvie upotrebljavani u medicini su danas preparati iz grupe psiholeptika. Ovim imenom se oznaavaju svi oni lekovi
koji, ispoljavajui svoje dejstvo u oblasti modanog stabla, redukuju stanja poviene psihike aktivnosti mozga i time oduzimaju
snagu centralnom nervnom sistemu. Dalja njihova diferencijacija dovodi ih do podele na: hipnotike, ataraksike i neuroleptike.
Hipnoticima se nazivaju takva sredstva koja izazivaju vetaki san, a mogu biti barbiturnog i nebarbiturnog porekla.
Veoma se mnogo koriste u medicini ne samo u psihijatrijskoj, ve i u bolesnika iz svih ostalih grana medicine. Njihova nekontro-
lisana upotreba veoma je iroka i u pripadnika tzv.zdrave populacije. U nae vreme ova sredstva se najee koriste namerno u
samoubilake svrhe, ili kao zadesna prilikom intoksikacija u dece.
Ataraksicima ili anksioliticima se naivaju oni medikamenti koji ublaavaju stanja straha, psihike napetosti i uznemire-
nosti, a uz to deluju blago antikonvulzivno, dok na periferiji izazivaju smanjivanje miine napetosti. Veruje se da je potronja
ovih lekova enormna u celome svetu. Meutim, nema sumnje da se i pri stogo racionalnom doziranju javlja opravdana potreba
za visokim konzumiranjem ataraksinih preparata. Rizici koji prate upotrebu ataraksika su mogunost navikavanja i pojava zavi-
snosti od ovih medikamenata (tabletomanije).
Neuroleptici deluju sedativno, nenarkotiki u terapijskim dozama, obuzdavajui psihomotorni nemir, u prvom redu psi-
hoza, i utiui pozitivno na shizofrene i manine sindrome. Antipsihotini efekt ovih preparata ogleda se, pre svega, u kupiranju
produktivnih psihotinih fenomena (halucinacije i sumanute ideje), a u neto blaem obimu i deficitarnih i regresivnih psiho-
patolokih pojava. Lekovi iz ove grupe (tzv.bazini, sedativni i snani neuroleptici) doveli su do radikalnih promena u psihijatri-
ji i olakali humanizaciju postupanja sa psihijatrijskim bolesnicima. Nasuprot pozitivnom sedativnom i antipsihotinom efektu,
neuroleptici iz razliitih grupa raspolau i nepoeljnim motornim fenomenima ekstrapiramidnog tipa i vegetativnim pojavama.
Mogunost pojave paroksizmalnih i tardivnih diskinezija, kao i hipotenzivnih kriza nalaze korektivnu medikaciju sa antiparkinso-
nicima i analepticima.
Prvim dvema generacijama sada se pridruuje trea, a na pomolu je i etvrta generacija neuroleptika s manje nuzefe-
kata, a s dinamizirajuim i sve vie selektivnim delovanjem. Osim ovih osobenosti, danas postoje sintetizovani neuroleptici s br-
zim, prolongiranim (retard-oblici) i dugotrajnim dejstvom (depo.oblici).

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 Psihoanaleptici se dele na timoleptike i timeretike. Zajedniki pojam oznaava sposobnost odreenih supstanci da po-
diu nivo psihikog ivota, u prvom redu podsticanjem raspoloenja i voljno-nagonskih dinamizama. Osim ovih dveju podgrupa,
ovde se ubrajaju i psihostimulansi ili energizeri koji jednim dejstvom na opte stanje organizma takoe deluju analeptikim efek-
tom. Dugo vremena u medikamentoznoj terapiji depresija vodee mesto pripadalo je inhibitorima monoaminooksidaze. Oni su
odigrali vanu ulogu, jer je uz njihovu pomo dolo do uspostavljanja kateholaminske teorije o nastanku depresija. Upravo dej-
stvo MAO inhibitora zasnivalo se na njihovoj osobini da poveaju sadraj monoamina u mozgu uz istovremeno koenje njihove
intracelularne metabolike razgradnje. Primena MAO inhibitora je bila praena brojnim nuzefektima, posebno od strane kardi-
ovaskularnog, renalnog, hepatinog, retikuloendotelijalnog i autonomnog nervnog sistema, pa je vremenom naputena.
Posle naputanja MAO inhibitora u terapiju depresija uvedeni su triciklini antidepresivi s reprezentantom imiprami-
nom. Ovaj preparat, posle izvanrednih rezultata, sve manje je imao mesta u terapiji depresija, ali je znaajan po neto drugai-
jem mehanizmu dejstva. On ne deluje na enzimatske procese razgradnje i sinteze moanamina, ve koi aktivni transport nora-
drenalina i 5-hidroksitriptamina u sinaptozome.
Danas su drugi preparati iz grupe antidepresiva triciklini i tetraciklini zauzeli vodee mesto u leenju depresivnih
sindroma.
Psihodizleptici kao supstance sposobne da menjaju aktivnost centralnog nervnog sistema nisu nali svoje mesto u me-
dicinskoj praksi i njihova upotreba nosi mnogo vee rizike nego koristi.

MEHANIZAM DELOVANJA PSIHOTROPNIH LEKOVA

V.M. Varagi
Razumevanje mehanizma delovanja psihotropnih lekova intimno je povezano s boljim razumevanjem metabolizma biolo-
ki aktivnih supstancija u velikom mozgu, pre svega biogenih amina (kateholamini, 5-hidroksitriptamin, histamine). Per analo-
giam se moe pretpostaviti da e i u centralnom nervnom sistemu, ba kao i na periferiji, najosetljiviji prema dejstvu lekova biti
procesi neurohumoralne transmisije nadraaja. U centralnom nervnom sistemu postoji vei broj bioloki aktivnih supstancija
koje vre ulogu transmitera nadraaja, ili su pak sposobne da deluju kao modulatori te transmisije. Ipak, daleko najvei znaaj
ima sposobnost psihofarmaka da promene metabolizam kateholamina (dopamine, noradrenalina, adrenalina) u velikom moz-
gu. Poseban znaaj imaju novija saznanja o sistemu ciklinog adenozin monofosfata u mozgu, o delovanju lekova na adrenalinu
ciklazu, o identinosti dopaminskog receptora i adenilne ciklaze u nekim strukturama mozga. Veliki broj psihofarmaka upravo
deluje na ovaj osetljivi system, to podrazumeva da se na ovaj nain menja ne samo receptorna aktivnost, ve i metabolike ka-
rakteristike neurona.

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ZNAAJ EKSTRAPIRAMIDALNIH POJAVA KOD PRIMENE PSIHOFARMAKA

B.Ignjatovi, D.Jevdi, B.Vukovi, D.Jovanovi i D.Milovanovi

Sloenost mehanizma dejstva psihotropnih droga u dananje vreme nesumnjivo izaziva veliko interesovanje. Pored sposob-
nosti da modifikuju mentalnu aktivnost oveka, da utiu na ponaanje, preko metabolizma mozga, one izazivaju i iznenadne se-
kundarne pojave, esto intezivne i ponekad alarmantne, akoje su grupisane pod optim nazivom sindrom impregnacije. Ove
supstancije su, dakle, podjednako sposobne da vre svoje dejstvo na izvesne nervne strukture, kortikalne i supkortikalne, koje
neprekidno kontoliu motorne, tonine, posturalne ili refleksne aktivnosti, ili tanije reeno, aktivnost efektornog sistema.
Danas ne samo da je to prihvaeno, ve je i dokazano da se dejstvo neuroleptika odvija uglavnom u nivou retikularne
formacije modanog stabla, bilo direktno ili indirektno, zvog njenih releja sa svim ostalim centralnim nervnim strukturama. Tako,
od donje bulbarne regije do hipotalamusa izvesni delovi su stvarno u tesnoj vezi s malim mozgom, drugi predstavljaju anatom-
ski supstrat aktivatornih i inhibitornih sistema, ulaznih i silaznih, koji su meusobno povezani i u vezi s korteksom, talamusom,
hipotalamusom, sivim jedrom i rinencefalonom.
Ova retikularna formacija predstavlja strukturu u isto vreme dinamogenu i inhibitornu, koja istovremeno regulie kor-
tikalnu i medularnu aktivnost, a osobito kontrolie monosinaptike reflekse.
Retikularna aktivnost je na taj nain potinjena jednom intracerebalnom kruenju retikulo-kortiko-retikularnoj retro-
akciji, inhibitarnom dejstvu, koje se moe prikljuiti klasini fronto-retikularni put, ija aktivnost pojaava dejstvo bulbarne in-
hibitorne mreaste formacije.
Polazei od ovih podataka, moe se osmotriti mehanizam neurofiziolokog dejstva neuroleptika u determinizmu sin-
droma impregnacije.
Prouavajui dejstvo psihotropnih droga J. Rigal i sar. su obelodanili njihovo dejstvo na sisteme alfa i gama koji kontro-
liu aktivnost motornih elija prednjeg roga.
Dokazano je da flufenazin u visokim dozama stimulie, ahloropromazin deprimira sisteme alfa i gama, te otuda podela
neuroleptika na snane (otre) i sedativne. Snani neuroleptici, kao to su flufenazini, stimuliui alfa i gama sisteme, prouzor-
kuju ekstrapiramidalne pojave, a sedativni, kao to su hlorpromazin, deprimirajui ove sisteme, spreavaju pojavu istih.
Prema tome, ekstrapiramidalne pojave izazvane snanim neurolepticima mogu se predvideti, preduhitriti, ili ublaiti
dodavanjem nekog drugog sedativnog neuroleptika.
Mi smo na naem materijalu, u 84 shizofrenih psihoza, ordinirali kombinovanu terapiju sedativnih neuroleptika (levo-
mepromazin, tioridazin i hlorpromazin) pojedinano uzetih, uz flufenazin (moditen) i jedan antiparkinsonik (artane) postigli
sledee rezultate: znatno poboljanje u 41, delimino poboljanje u 35 i neuspeh u 8 bolesnika. Ekstrapiramidalne pojave nismo
oekivali, pa se iste nisu ni pojavile.
U literaturi postoje dva suprotna stava o terapijskom znaaju neurolokij sindroma izazvanih neurolepticima. Dok jed-
ni smatraju da neuroloke pojave poseduju odreen terapijski efekt, te ih treba provocirati, dotle drugi misle da su one suvine
i nepoeljne.
Pristalice prvog shvatanja navode korisnot ekstrapiramidalnih pojava za ishod leenja, pa smatraju da postoji i korela-
cija itmeu intenziteta ekstrapiramidalnih simptoma i stepena poboljanja mentalnih oboljenja. Oni su protiv spreavanja ek-
strapiramidalnih pojava uvoenjem antiparkisonika koji, po njima, remete procenu dejstva neuroleptika.
Pobornici suprotnog stava predlau paralelnu primenu neuroleptika i antiparkisonika, jer smatraju da je nehumano i
protivno lekarskoj etici namerno izazivati ekstrapiramidalne pojave koje bolesnici muno doivljavaju, a pored toga postoje i hi-
poteze da bi mogle prei u hronine.
D. Milovanovi u svojoj knjizi Klinika psihofarmakoterapija navodi da su u bolesnika leenih neurolepticima paroksiz-
malne diskinezije registrovane u 24% sluajeva, a u bolesnika leenih kombinovanom terapijom nije bilo zapaeno ispoljavanje
paroksizmalnih diskinezija i ostalih neurolokih sindroma neuroleptikog porekla. U prvih su postigli znatno poboljanje u 77%
sluajeva, a u drugih u 80% sluajeva.
Prema gore navedenim rezultatima, a takav je i na stav, terapijski efekat neuroleptika je jednak, bez obzira na to da li
se oni primenjuju sami ili zajedno sa antiparkinsonicima. S druge strane, paralelna primena neuroleptika i antiparkinsonika one-
moguuje pojavu ekstrapiramidalnih siptoma.
Prema klinikim rezultatima NPK u Beogradu, negira se terapijska vrednost paroksizmalnih diskinezija, pa samim time
i potreba za namernim provociranjem.
U novije vreme otkriem slozapin-a (leponex-a) dolo je do novog zaokreta u miljenjima i stavovima. Tako, dok su ranije
novosintetizovana jedinjenja bila kliniki prouavana samo ako su ve ispoljila znaajnu kateleptiku aktivnost u eksperimentima
na ivotinjama, danas to vie nije pravilo. Clozapin ima isti terapeutski efekat kao i klasini neuroleptici, ali se razlikuje od njih
u tome to ne utie na ekstrapiramidalne pojave pri eksperimentu na ivotinjama, niti pri aplikaciji na ljudima. Po hemijskom
sastavu clozapin je blizak klasinim neurolepticima.
Gross i Langer su potvrdili nalaze Bente-a (1966 g.) i Berzewsky-a (1969 g.) da je terapeutska efikasnost triciklinih ne-
uroleptika nezavisna od njihovog efekta na ekstrapiramidalne funkcije.
Biohemijskim istraivanjima je dokazano da clozepin, kao i klasini neuroleptici, utie na metabolizam dopamina, tj.u
shizofrenih bolesnika dovodi do porasta kocentracije HVA (homo vanilinske kiseline) u mozgu, ali suprotno klasinim neuro-
lepticima, utie i na metabolizam norepinefrina.

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 Primenjujui i ispitiujui clozapin u shizofrenih psihoza, odnosno u 61 bolesnika, postigli smo sledee rezultate: znatno
poboljanje u 35 ili 57,4%, delimino poboljanje u 21 ili 34,5% i neuspeh u 5 ili 8,1%. Ekstrapiramidnih pojava nije bilo, te ih nismo
mogli ni da registrujemo.

ZAKLJUAK
Ekstrapiramidalne pojave koje daju snani neuroleptici stimuliui alfa i gama sisteme nisu vue dokaz terapijske vre-
snosti. Sedativni neuroleptici u kombinaciji sa snanim neurolepticima smanjuju pojave ekstrapiramidalnih siptoma, a dodava-
njem atiparkinsonika ih spreavaju. Iz tih razloga ekstrapiramidalne pojave ne treba provocirati, ve suzbijati.
Neuroleptici koji ne utiu na ekstrapiramidni sistem, te na taj nain i ne daju ekstrapiramidalne pojave (clozapine) mogu
da ispoljavaju snano antipsihotino dejstvo kao i klasini neuroleptici.

135
KLINIKI ASPEKTI HRONINIH NEUROLEPTIKIH POJAVA

B. Vukovi, B. Ignjatovi. D. Jevdi i D. Jovanovi

Da bi se mogla pratiti problematika koja nastaje u vezi sa sporednim efektima i komplikacijama primene neuroleptike
terapije, neophodno je poznavanje klinike slike, naina leenja i profilakse.
Ove pojave su veoma raznolike, one zavise od individualne osetljivosti organizma, ali i niza drugih faktora, a javljaju se
kao rezultat direktnog dejstva preparata na organizam. S terapijskog aspekta vana je diferencijacija ovih pojava koje u najopti-
jem smislu moemo razdvojiti na povratne ili funkcionalne i nepovratne odnosno organske. Pri ovakvoj orijentaciji neemo se
zadravati na pojavama kratkotrajne primene, niti pak na akutnim pojavama koje prate dugotrajnu primenu. Zadovoljiemo se
time da ih samo spomenemo.
Dugotrajnu primenu neuroleptika, kao i ukidanje istih, prati niz izraenih komplikacija koje se mogu obuhvatiti u jedin-
stvenu pojmovnu celinu hroninog ekstrapiramidnog sindroma. Ovaj sindrom se javlja prilikom primene svih psihotropnih le-
kova (trankvilizeri, antidepresivi), ali daleko najee uz primenu neuroleptika.
Ove komplikacije perzistiraju mesecima i godinama i ne pokazuju tendenciju regrediranja. Pojam i znaaj ovog sindro-
ma najbolje se moe sagledati iz klinike slike koju smo iz didaktikih razloga pratili kroz tri sledee komponente:
Ekstrapiramidni znaci: oralne diskinezije, atetoidno-horeiformne hiperkinezije, mioklonije, tremor, hipertoniko-akinetiki
sindromi i akinetiki sindrom.
Psihiki znaci: psihika pasivnost, aspontanost, redukcija motivacija i sumanutih ideja, emocionalna nepostojanost sa psi-
hikim hiperestezijama, anksioznost.
Vegetativni znaci: poremeaj rada srca, vaskularnog tonusa, motorike i sekrecije digestivnog trakta, znojnih i lojnih lezda.
Ove znake prate poremeaji metabolizma masti, vode i soli, hipovitaminoze. Uz ove javljaju se i poremeaji endocrine regulacije.
Ova trijada znakova ini sutinu hroninog ekstrapiramidnog sindroma.
Biohemijski aspekti: ovde je naroito vano zadrati se na pojavama koje nastaju posle ukidanja neuroleptike terapije.
Ukidanje izaziva, ili jako potencira pojavu hiperkinetikog poremeaja. injeni su pokuaji da se ova pojava objasni, oslanjajui
se na hipotezu Pletcher-a, priguenjem biogenih amina: kao kompenzatorna pojava u tkivima mozga stvara se viak monoami-
na koji, pak, uzrokuje sindrom liavanja. Ovu teoretsku postavku neki autori su pokuali da iskoriste za postavljanje hipoteze
o narkomanskom privikavanju na neuroleptike. U prilog ovome spomenimo da Prokudin (1912) smatra da se pri ovome formira
kompulsivna zavisnost od neuroleptika, koju prati i psihika, to se manifestuje pojavom straha i neurotskih smetnji pri liavanju.
Battegay koji daje najiscrpnije opise ovih zavisnosti smatra da postoji mogunost nastajanja fizike zavisnosti, bez pojava
psihike zavisnosti, povienja tolerancije i samim time apstinencijalnih kriza.
Terapijske specifinosti: Hronini ekstrapiramidni sindrom je gotovo rezistentan prema antiparkinsonskim lekovima. Ovde
se postie olakanje detoksikacionom terapijom: glikoze s vitaminima, male doze insulina, fizioloki rastvor NaCl supkutano; ta-
koe preparati broma i trankvilizeri oralno.
Lokalne diskinetike smetnje mogu se olakati uvodjenjem kokaina ili sedativnih doza largaktila.
Pojedina stanja (akatizija, tazikinezija, hiperkineza tipa hodanja, tahikinezija i sl.) uglavnom se kupiraju, pored antipar-
kinsonika, i meprobamatom.
U zakljuku ovoga rada pokuaemo da damo odgovor na neka od sutinskih pitanja problema o kome raspravljamo.
Problem optimalne duine primene neuroleptike terapije svakako je jedan od osnovnih. Odgovor na ovo pitanje moe da pru-
i provera biohemijskih nalaza, kao to je patoloki nalaz holesterola, transaminaza, elektorforeze serumskih proteina, timola,
bilirubina, u tom smislu to bi njihovi odreeni pokazatelji bili indikator za prekid neuroleptike terapije.
Kao drugo, namee se pitanje koji od ovih poremeaja ostaju kao aktivno nepovratni neuroloki, u tom smislu i psihi-
ki poremeaji. U odgovoru na ovo pitanje, napominjemo da se naa iskustva baziraju na praenju grupe bolesnika tokom dugo-
trajne neuroleptike terapije i posle njenog ukidanja.
Zapazili smo da u priblino jedne polovine sluajeva nema nikakvih klinikih znakova sporednih efekata i komplikacija.
U ostalog dela bolesnika zapaene su manifestacije apstinencijalnih znakova i kriza (kompulsivnost). Ipak, u veine ovog, drugog
dela posmatrane grupe zabeleene su komplikacije ekstrapiramidne simptomatologije. Ovde je interesantno spomenuti da se
ove komplikacije i efekti ee javljaju u ena.
Na zavretku elimo da istaknemo da smo duboko svesni injenice da ovo nisu ni pravi ni potpuni odgovori. Bili bismo
veoma zadovoljni ako bi na rad, makar i u neznatnoj meri, uneo izvesnu svetlost u zamrenost ove problematike.
Pitanja kojih smo se dotakli ostaju i dalje otvorena, odgovor na njih, nadajmo se, jeste delo budunosti.

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DILEME PRI UPOTREBI PSIHOFARMAKA

B. Ignjatovi, B. Vukovi, D. Jevdi, D. Jovanovi i S. Bokorov

Mesto i uloga psihofarmaka u dananjim uslovima su veoma znaajni, i to ne samo u psihijatriji, ve i u drugim granama
medicine. Danas se zaista dosta zna o primeni psihofarmaka u neurologiji, internoj medicini, pedijatriji, hirurgiji, infektologiji,
ginekologiji i akuerstvu. Posebno bi moda moglo da se govori o uslovima i potrebama da se prouavanjem psihofarmaka, od-
nosno psihofarmakoterapijom pozabave i bolje upoznaju ne samo specijalisti gore navedenih grana, ve i lekari opte medicine.
Najvei broj bolesnika s funkcionalnim smetnjama razliitih organa po pravilu se najpre obraa za pomo lekaru opte
medicine ili specijalisti interne medicine. Ukoliko ne upute bolesnika psihijatru, ili iz bilo kojih razloga nemaju mogunosti i vre-
mena za to, oni su, hteli ili ne, u situaciji da prepiu neko od sredstava sa psihotropnim delovanjem. Neurovegetativne cistonije,
psihosomatska oboljenja, hipertenzije granina su indikaciona podruja interniste i psihijatra. Iz tih razloga internista je upuen
ne samo na saradnju sa psihijatrom. Ve mu je za kliniku praksu potrebno da poznaje osnove psihofarmakoterapije.
Specifinosti dejeg doba opravdano nalau posebnu obazrivost pri upotrebi psihofarmaka. Kao to je ve poznato,
deca pokazuju izuzetnu osetljivost prema psihofarmacima, a psihofarmaci se pak odlikuju mnogobrojnim nuspojavama drama-
tinog izgleda, te se mora voditi rauna o racionalnoj i kontrolisanoj upotrebi psihofarmaka u pedijatriji.
Od ne manjeg znaaja je upotreba psihofarmaka u hirurgiji. Kod izbijanja operativnih i postoperativnih konfuzno-de-
lirantnih stanja hirurg nema vremena da se razmislja i da eka, ve mora odmah da se odlui koji psihofarmak i u kojoj dozi da
primeni. Prilikom predoziranja butirofenona moe da se kao znak intoksikacije javi dramatina klinika slika akutnog abdome-
na, a bolovi mogu biti izmenjeni, potisnuti ili provocirani pod uticajem psihofarmaka, te i o tome treba voditi rauna. Shizofreni
bolesnik esto puta zbog gubitka afekta, osnosno emocionalne tuposti koja se ispoljava u apatiji i ravnodunosti, kao i zbog ne-
sklada drai i afekta (paratimija), nesklada izmeu afekta i mimike (paramimija) ne daje adekvatne podatke, daje suprotne ili ni-
kakve, tj.ponaa se suprotno od onoga to se u njemu zbiva.
Iz linog iskustva znamo da su se neki nai bolesnici ponaali neadekvatno u stanjima postojeeg ileusa, te smo pored
povraanja, bledila i napetog trbuha zapazili potpunu ravnodunost prema postojeim tegobama, a u nekih ak i osmeh na licu.
Zbog svega ovoga se javljaju potekoe u dijagnostici ileusa u nekih shizofrenih bolesnika, pa se samim time namee i potreba
za veom i uzajamnom saradnjom hirurga i psihijatra.
Infektivne bolesti predstavljaju posebno mesto za saradnju infektiologa i psihijatra. Sigurno je da i ovde psihofarmaci
imaju znaajnu ulogu u suzbijanju psihomotornog nemira i insomnije u akutnih afekcija CNS izazvanih raliitim noksama, kao i
pri upotrebi diazepama u terapiji tetaunusa.
Sindrom menopauze, usled brojnih polimorfnih psihikih somatskih tegoba za najbolji pristup u terapiji, zahteva upravo
saradnju psihijatra, ginekologa i endokrinologa. Kod trudnica za vreme poroaja savremeni psihofarmaci mogu da ublae strah
i otklone afektivnu napetost. Eklamptina stanja, takoe, zahtevaju pravilan pristup leenju. Sigurno je da ne treba biti u dilemi
prilikom intervencije i odluivanja koji psihofarmak dati i u kojoj dozi. Da li e to biti fenobarbiton, litiki koktel, hlorpromazin
ili diazepam, zavisie od naeg poznavanja, iskustva i poverenja u odgovarajui psihofarmak.
Posebno mesto u zajednikom tretmanu imaju psihijatar i lekar opte medicine pri primeni psihofarmaka kod neuro-
tinih sindroma, alkoholozma, akutne alkoholisanosti, apstinencijalnog sindroma u alkoholiara, patolokog napitog stanja, tok-
sikomanije, epilepsije i dr.
Iz gore navedenih injenica moe se izvesti kratak zakljuak da se primenom psihofarmaka i u ostalim granama medi-
cine osea sve vea potreba za saradnjom, kao i veim poznavanjem uloge i dejstva psihofarmaka, a sve to radi pravilne i racio-
nalne primene, radi postizanja to boljeg afekta i uspeha u leenju.
Posle ovoga, namee se potreba da neto kaemo o psihofarmacima, kao i o psihofarmakoterapiji u domenu psihijatrije.
Psihofarmakoterapija je vrlo jednostavan i praktian metod leenja, pa je pogodna kako u hospitalnim tako i u ekstra-
hospitalnim uslovima. Pojavom prvih psihofarmaka psihofarmakoterapija poinje da probija sebi put postiui sve bolje rezul-
tate u leenju psihijatrijskih bolesnika, a sledstvenim poveanjem broja psihofarmaka postie zavidan uspeh u psihijatriji, kakav
ranije nije postigao nijedan drugi metod leenja (piretoterapija, insulinoterapija, elektokonvulzivna terapija i psihoterapija).
Psihofarmaci su aktivne hemijske supstance koje se vezuju za pojedine strukture mozga i na taj nain otklanjaju, ubla-
avaju ili izazivaju mentalne poremeaje. Oni mogu da modifikuju aktivnost CNS, da utiu na ponaanje oveka, da ga menjaju,
te ih po tome Delay i Deniker dele na: psiholeptike koji deluju deprimirajue, sedativno na normalne ili pojaane funkcije CNS;
psihoanaleptike koji deluju stimulativno, ekscitativno na normalnu ili snienu funkciju CNS; i psihodisleptike koji ispoljavaju per-
turbantno dejstvo na normalnu psihiku aktivnost.
Meu psihofarmacima osnosno psiholepticima najvanije mesto zauzimaju neuroleptici koji imaju sposobnost da sma-
njuju psihomotornu hiperaktivnost, redukuju pojavu akutnih, hroninih i eksperimentalnih psihoza, a dejstvom preko hipotala-
minoretikularne oblasti da stvaraju i znaajne neurovegetativne i ekstrapiramidne manifestacije. Njihova je zasluga to su psi-
hijatrijske bolnice izmenile svoj lik, a psihijatri svoj odnos prema psihijatrijskom bolesniku.
Radi bolje pregledanosti i celishodnije primene u psihijatriji Lambert i Revol su ih 1960.godine podelili na derivate s leve
strane, kao najsedativnije, iji je predstavnik levomepromazin, derivate s desne strane, kao najsnanije anipsihotike, iji je pred-
stavnik tioproperazin, i derivate sa intermedijarnom pozicijom koji poseduju sedativno i antipsihotino dejstvo, a iji su pred-
stavnici hlorpromazin, rezerpin i tioridazin.
Vano je napomenuti da neuroleptici u manjim dozama imaju samo psiholeptiko dejstvo, a u veim i hipnotiko. Sedativni
pak neuroleptici u veim dozama ispoljavaju i antipsihotino, a antipsihotini u veim dozama imaju i sedativno dejstvo.

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 Samim tim se namee i pravilo: za postizanje odgovarajueg efekta potrebna je odgovarajua doza. Na primeru flufenazina
moe se mnogo nauiti kad su u pitanju doze i razliiti efekti ispoljavanja. Tako, flufenazin u malim dozama do 2 mg dnevno je kori-
stan za tretiranje stanja anksioznosti i napetosti. U dozi od 2,5 do 30 mg dnevno ispoljava antipsihotino, ali ne i sedativno dejstvo.
Neki autori ovako opisuju polivalentno dejstvo flufenazina: umirujue dejstvo 0,5-5 mg; anksiolitiko 100-200 mg; se-
dativno 100-1.200 mg; antipsihotino 5-1.800 mg dnevno.
Amerikanci i Francuzi su upotrebljavali mnogo vee doze flufenazina, jer su zapazili da se ekstrapiramidne pojave sma-
njuju ako se doze flufenazina progresivno poveavaju. Najbolje rezultate su postigli aplikacijom flufenazina u opsegu od 150-750
mg dnevno.
Ne treba zaboraviti da je flufenazin 20 puta jai od hlorpromazina, te se ne savetuje upotreba visokih doza ako se po-
eljni efekti postignu manjim dozama.
esto se za neuspeh od nekih autora okrivljuje neadekvatna doza.
Kad se postigne terapeutski efekt, savetuje se postepeno smanjivanje leka do doze odravanja. Naglo i suvie brzo sma-
njenje moe da dovede do relapsa (pogoranja bolesti), te i o tome voditi rauna.
Vano je voditi rauna o predoziranju, a isto toliko i o nedovoljnom doziranju. I u jednom i u drugom sluaju treba po-
tovati linost bolesnika.
Kod predoziranja bolesnik je obino usporen, inhibiran, pasivan, vie ili manje nesvestan svojih poremeaja, somno-
lentan. Zato se ne ali na svoje tegobe i podnosi ih pasivno i ravnoduno. Po pravilu, bolesnikova okolina upozorava na njegovu
apatiju, usporenost i somnolenciju. Predoziranje moe takoe odravati ili prouzorkovati psihotine poremeaje, aktivirati ili
pojaati halucinacije. Ove pojave nestaju nakon naglog smanjenja doze.
Kod nedovoljnog doziranja bolesnici su mrzovoljni, pasivni, mrgodni, ale se na brzo zamaranje, depresivne tendencije,
a posebno su optereeni postojeim psihopatolokim sadrajem. Svi ovi simptomi nestaju kad se poveaju doze.
Na primeru flufenazina mogli bismo da izvuemo neka korisna iskustva i pri primeni drugih neuroleptika.
Smatramo da bi nae izlaganje bilo nepotpuno ako ne bismo neto rekli i o pitanju terapijskog pristupa. Klasian stav u
terapijskom pristupu je nozoloki, ali u hitnim sluajevima da etioloki odreujemo morbidnu kategoriju nemamo vremena, te
se primenjuje sindromoloki pristup, gde se daje ciljani psihofarmak na ciljane postojee siptome i sindrome. Za ciljani pristup,
pored dobrog poznavanja simptoma, potrebno je i dobro poznavanje osobina jednog leka. U okviru ove ciljane psihofarmakote-
rapije ponikao je i pojam target ciljanih simptoma. Target simptomi bi bili oni na koje pojedini psihofarmaci uspeno deluju.
Hertrich je 1965.godine proirio prvu listu target siptoma od 5 na 9 sindroma, a koja danas izgleda ovako:
Sindrom psihomotornog nemira;
Sindrom akutnog straha i anksioznosti;
Sindrom stupora;
Sindrom autizma;
Paranoidni sindrom;
Manini sindrom;
Depresivni sindrom;
Halucinatorni sindrom; i
Sindrom mentalne konfuzije.
D. Milovanovi je u svojoj knjizi Klinika psihofarmakoterapija iznosi da nema otre granice izmeu sindromolokog i nozolo-
kog pristupa, da su oba celishodna i da se u toku celokupnog leenja skladno dopunjuju. Zatim kae da na poetku leenja najpre
treba primeniti sedativne neuroleptike, a posle suzbijanja psihomotornog nemira primeniti pravu ciljanu antipsihotinu terapiju.

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DIHYDROERGOTAMIN- METANSULFONAT (DITAMIN) U LEENJU
GLAVOBOLJA
Postignuti su dobri rezultati aplikacijom Dihydroergotamine-methanesulfonatae (Ditamin) kod onih pacijenata koji su
imali glavobolju praenu ortostatskom hipotenzijom. Medikament je primjenjivan ambulantno, u dozi od 25 kapi ujutro i 50 kapi
uvee.

UVOD
Danas se glavobolja veoma esto pojavljuje u ambulanti lekara opte medicine. Mogunosti za njeno leenje, pri prvom
susretu sa bolesnikom, su nedovoljne i nezahvalne, pogotovu ako bismo hteli da postignemo neki zadovoljavajui uspeh. Uzroci
glavobolja su raznovrsni i mnogobrojni, te je za efikasna tretman, potrebno postaviti pravilnu dijagnozu. Iz tih i drugih razloga
takvi pacijenti se najee upuuju neuropsihijatru.
U dananje vreme se mnogo vise zna o etiologiji i patofiziologiji glavobolja, pa shodno tome postoje i mnogobrojne kla-
sifikacije. Moderno leenje vaskularnih glavobolja, to je predmet naeg izuavanja, poinje otkriem ergotamina 1918 (Stoll),
kao i primenom istog kod migrene 1926 (Mayer). U leenju glavobolja prednost ima kauzalna terapija, ali je nesumnjivo od zna-
aja i simptomatska terapija. Da bi se postigao to bolji uspeh u leenju, vano je da se zna, da dejstvo jednog leka ne zavisi
samo od njegovog farmakodinamskog svojstva, ve i od pravilne i blagovremene primene, koliine i oblika leka, kao i moguno-
sti resorpcije.
Smatra se da su dilatacija, distenzija, dislokacija i trakcija bolno osetljivih arterija mozga najei uzrok glavobolja in-
trakranijalnog porekla, a zapalenje, pritisak i istezanje pak uzroci glavobolja ekstrakranijalnog porekla. Veina glavobolja poinje
kratkotrajnom vazokonstrikcijom, koja izaziva prodromske simptome, posle ega
usledi dugotrajne vazodilatacija i distenzija s konsekutivnim edemom u zidu i oko arterija, a takoe i snienim pragom na-
draaja za bol. Bol iz intrakranijalnog prostora se prenosi iradijacijom preko modanog stabla, talamusa i kimene modine u
tipine segmente, kao kod angine pektoris, i tako izaziva glavobolju.
Sve je ovo veoma znaajno, radi blagovremene i pravilne primene leka, jer je poznato da dihidroergotamin-metansul-
fenat (Ditamin) izaziva vazokonstrikciju ili vazodilataciju, zavisno od postojeeg tonusa krvnih sudova, pa se sledstveno tome
moe primenjivati u profilaksi i terapiji glavobolja.

CILJ RADA
U radu je praen efekat leka dihidroergotamin~metansulfonata (Ditamin) kod pacijenata koji su po naem nalazu bo-
lovali od klasine migrene, atipine migrene i neurotine glavobolje. Posmatranjem smo nastojali da pomou uobiajenih
para-metara prikaemo mehanizam dejstva ovog leka na postojee simptome navedenih glavobolja.

METODOLOGIJA
U naoj grupi pacijenata sa simptomima glavobolja, od kojih su mnoge praene i ortostatskim smetnjama, uzeti su po-
trebni anamnestiki podaci i izvreni neuroloki i somatski pregledi, te tako iskljuena organska obolenja.
Dihidroergotamin-metansulfonat (Ditamin) smo ordinirali oralno u dozi od 25 kapi ujutru i 50 kapi uvee u vremenu
od 30 dana, zatim pauza 30 dana, a zatim ponovo primena leka 30 dana. Kod tri pacijenta smo uveli dodatnu terapiju zbog po-
stojeih neprijatnih neurotskih smetnji. Kod jedne pacijentkinje smo morali da prekinemo lek zbog upornih povraanja.
Kontrolne preglede i razgovore sa pacijentima smo vrili na 7, 14, 30 i 60 dana od poetka uzimanja leka.

REZULTATI
U ispitivanje je bilo ukljueno 30 bolesnika i to 24 ena i 6 mukaraca od 22 do 55 godina starosti. Po dijagnostikoj strukturi
zastupljenost je bila sledea: klasina migrena 11, atipina migrena 7 i cephalea neurotica 12 pacijenata. Na kraju ispitivanja
sumiranjem rezultata zabeleili smo sledei uspeh: znatno poboljanje (+++) kod 10 pacijenata ili 33,33%, delimino poboljanje
(++) kod 16 pacijenata ili 53,34 + i neuspeh (o) kod 4 pacijenta ili 13,33 %. Uspeh rasporeen po dijagnozama izgledao bi ovako:
klasina migrena +++ kod 7, ++ kod 4 i kod O pacijenata
atipina migrena +++ kod 2, ++ kod 3 i kod 2 pacijenta,
cephalea neurotica +++ kod 1, ++ kod 9 i kod 2 pacijenta.
U toku ispitivanja primetili smo da je na lek reagovalo sa poboljanjem glavobolja i drugih prateih simptoma odree-
ni broj pacijenata u sledeoj zastupljenosti: odmah nastalo poboljanje kod 8, treeg dana kod 9, sedmog dana kod 4, desetog
dana kod 2, etrnaestog dana kod 5, i bez poboljanja kod jednog pacijenta.
Kod osam pacijenta ija je glavobolja bila praena ortostatskom hipotenzijom, pored poboljanja simptoma glavobolje
dolo je i do popravljanja hipotenzije od 100/70 na 120/80 u toku prvih nekoliko dana.

SPOREDNI EFEKTI ISPITIVANJA

Samo jedna pacijentkinja se alila u toku prvih 9 dana na uporna povraanja posle uzimanja leka, te smo isti morali da
prekinemo, a nju iskljuimo iz daljeg ispitivanja.

139
ZAKLJUAK
Dihidroergotamin- metansulfonat (Ditamin) se pokazao efikasnim lekom kod neurotinih glavobolja, klasinih i ati-
pinih migrena, kao i glavobolja praenih ortostatskom hipotenzijom. subjektivno se dobro podnosi i praktino je bez toksinih
i drugih sekundarnih neeljenih pojava. U toku ispitivanja nismo zapazili neke izmene u laboratorijskim, biohemijskim, rentgen-
skim i EEG nalazima.
Preparate smo primenjivali ambulantski, pa smatramo da se moe ordinirati sa uspehom kod navedenih glavobolja i to
kako ambulntski tako i stacionirano.

LITERATURA
1) Anthony M.: The Management of Migraine. New Ethicals and Medical Progress, 1974. 2) Ivankovi D., Savi S., Misirli
T., Tubin M., i Dimitrijevi, l.: Terapija ortostatske disregulacije i nekih hipotenzivnih stanja dihidroergotamin-metansulfonatom.
Praxis medioi, vol. X, 1979. 3) Medicinska enciklopedija. Zagreb, MM LXVll. 4} Neurologija, Simpozij o neurologiji i psihijatriji,
Lek, Ljubljana, 1969. 5) Radojii B.: Klinika neurologija, Medicinska knjiga, Beograd-Zagreb. 1965. 6) Volans G.: Research Review
Migraine and Drug Absorption Clinical Pharmacokinetics 3:313-318, Adis Press, 1978.

DIHYDROERGOTAMINE-METHA-NESULFONATE (DITAMIN) IN
TREATING HEADACHE

Ignjatovi, B.
We applied Dihydroergotamine-methanesulfonate (Ditamin) and followed its effect in 30, patients, who had symptom
of headache. ln 8 patients these headaches were followed by Orthostatic Hypotension. The testing was done out of hospital;
the drug was given oralv 25 drops in the morning and 50 drops in the evening.
Efficacy in removing the existing symptoms of headache and the associated Ortohostatic Hypotension were noted by
us in the greatest number of cases in the course of rst days. Only one patient-girl had complication in the form of, constant
vomiting and we were forsed to stop that treatment.
Due to the efficacy of the Ditamine, as well as its good tolerance, poor toxicity, and due to the fact that by effects are
negligible, this drug may be recommended in healing the headaches, especially those followed by Orthostatic l-lypotension.

BOIDAR IGNJATOVI, neuropsihijatar

Neuropsihijatrijska bolnica Dr Slavoljub Bakalovi
Vrac, Podvranska, 7

140
VEGETATIVNI POREMEAJI PRI UPOTREBI PSIHOTROPNIH LEKOVA
AUTORI
B. Vukovi, B. Ignjatovi, D. Jovanovi i D. Jevdi
Psihofarmaci, psihotropne supstancije. ispoljavaju psihoaktivno dejstvo u otklanjanju psihopatolokog sadraja, u po-
tiskivanju postojeih simptoma i sindroma i na taj nain zauzimaju vidno mesto u psihjatriji, odnosno, u savremenom pristupu
leenja psihoza i psihotinih ispoljavanja, ali pored tih svojih pozitivnih osobina oni ispoljavaju i neka neeljene dejstva u toku
njihove aplikacije. Tako, pored ve poznatih ekstrapiramidalnih pojava, neki od njih izazivaju i mnogobrojne vegetativne smetnje
na koje mi u naem referatu elimo da skrenemo panju, ne samo zbog znaaja istih, ve i zbog opasnosti koje mogu da prate
ove pojave, a koje se mogu preduhitriti razumnim voenjem terapije.
Ovi prolazni poremeaji funkcije autonomnog nervnog sistema uoavaju se najee pri leenju neurolepticima i an-
tidepresivima. Meutim, najkarakteristinije neurovegetativne pojave su kod primene antidepresiva. One su povezane, uglav-
nom, sa holinerginim efektom preparata, ali je teko rei ta uslovljava poremeaj vegetativne ravnotee priguenje funkcije
ili poveanje suprotnog uticaja.
Selbach (1957) izdvaja u dejstvu antidepresiva dve faze: poetnu, sa prevagom trofotropnog i narednu, sa prevagom
erogotropnog uticaja. Najizrazitije adrenolitike osobine poseduju proizvodi fenotijazna (Largactil Noznan). a, takoe, i tiok-
santeni. Largactil sniava TA od 10 - 40 a ponekad i do 70 mm Hg stuba. Neznatne hipotenzive osobine poseduju piperazinski
proizvodi fentotijazina (Lyogen, Terfluzine.Frenolon]. Rezerpin koji poseduje parasimpatino dejstvo, moe, takode, izazvati izra-
zitu hipotoniju. Hipotoniia se moe uoiti ve u prvim satima posle poetka leenja, pri malim dozama preparata. U isto vreme
se pojavljuje opasnost od nastanka ortostatskog kolapsa.
Hipotenzivni efekat se ispoljava skoro kod svih osoba pri primeni neuroleptika, naravno kod nekih ree, a kod nekih
ee i intenzivnije. Takoe ie zapaeno da je pad krvnog pritiska vei kod starijih osoba, arteriosklerotiara, hipertoniara i ve-
getativno labilnih. U literaturi je opisano nekoliko sluajeva smrtnog kolapsa, naroito kod prelaska iz leeeg u stojei stav.
Smanjenje arterijskoq pritiska pojavljuje se pri intravenskoi aplikaciji preparata i to srazmerno poveanju doze. Opasnost
ortostratskon kolapsa vea je u bolesnika starijeg uzrasta. Kod primene hlopromazina i rezerpina, u cilju spreavanja ortostat-
skog kolapsa, preporuuje se leanje u postelji od 1 do 2 asa posle svakog uzimanja preparata.
Neki preporuuju u oslabljenih bolesnika, kao i onih sa labilnim i smanjenim vaskulariim tonusom, u prvim danima te-
rapije neurolepticima profilaktinu primenu Carnigena, Sympatola i drugo. Takoe se smatra da je za otklanjanje ortostatskog
kolapsa dovoljno postaviti bolesnika u horizontalni poloaj podignutih nogu uvis, uz aplikaciju Sympatola. Pri tekom kolapsu,
pokazali su se efikasnim: adrenalin, noradrenalin, i efedrin. U sluaju neophodnosti ovi se preparati uvode nekoliko puta na dan.
peros ili intravenski sa fiziolokim rastvorom.
Kao drugi propratni, neugodan vegetativni poremeaj navodi se tahikardija za koju se ne preporuuje specijalno leenje
jer se smatra da je ona sama po sebi prolazna pojava. Meutim, ubrzanje pulsa ponekad moe da pree granice koje se toleriu
od 90-100 udara u minuti i dostigne od 100-130, a, po nekima, i preko 180 udara u minuti, pa se takvim sluajevima preporuuje
rezerpin, smanjenje ili ukidanje ordinirane psihotropne supstancije. Piperazinski proizvodi fenotijazina i butirofenona ne izazi-
vaju primetne tahikardije. Ponekad se javlja tahikardija i pri leenju antidepresivima (Tofranil, Anafralin).
U literaturi se opisuju i pravi infarkti, a neki od njih su se i fatalno zavrili. To nam skree panju da neuroleptici mogu
da budu i opasni prilikom primene, a naroito u starijih osoba, sranih bolesnika, arteriosklerotiara, te ih treba davati oprezno
i u manjim dozama. Sigurno je da srce mlaih osoba moe da izdri i vee optereenje kod primene visokih doza kao i dugotraj-
ne upotrebe leka.
Bradikardija je uoena ponekad pri leenju haloperidolom, rezerpinom i litijumom. esto je praena i ekstrasistolama,
bolom u srcu. oteanim disanjem i cijanozom. Dobri rezultati u otklanjanju ovih pojava postignuti su ordiniranjem korektora
(atropin, artane] i kardiotonika.
Vano je istai efekat neuroleptika i na unutar-sranu sprovodljivost. Demidova (1956) je zapazila umereni poremeaj unu-
tar predkomorne sprovodljivosti pri leenju Largactilom.
Uticaj neuroleptika na promene elektrokardiograma zapaen je od strane nekih autora, a najee se opisuje aplatiran,
odnosno, izmenjen zubac T, koji po svoj verovatnoi nema nekog klinikog znaaja. Promene na elektrokardiogramu ee su
bile izraene pri leenju Mellerilom i Largactilom. Zapaeni su i teki poremeaji srane sprovodljivosti sve do atrioventrikular-
ne blokade sa smrtnim ishodom (Kelly sa sard. 1965).
Roy i Scherrer (1972) ukazuju na komplikacije od strane kardiovaskularnog sistema koje se javljaju pri leenju antide-
presivima, najee Tofranilom (poremeaj ritma, ishemij, infarkt) itd. Mada su ove pojave retke, ipak se skree panja na po-
stojanje istih.
Druge vegetativne pojave, kao to su hiperhidroza, hipersalivacija, poremeaj akodomacije, esto se pojavljuju zajedno
sa ekstrapiramidalnim manifestacijama, i, u isto vreme, nestaju sa njima primenom antiparkisonih medikamenata.
Suvoa sluzokoe usne duplje i usnica je esta pojava kod primene neuroleptika i antidepresiva. Ove promene nastaju
usled antiholinerginog
efekta preparata, koji smanjuje sekreciju pljuvanih lezda. Oticanje sluzokoe nosa sa oteanim disanjem na nos, esta je
pojava na poetku terapije neurolepticima.

141
 Pri leenju neurolepticima, pored gore navedenih pojava, zapaena je i hipovitaminoza, (suv, presvuen skramom ili
crven jezik. ispucale usne, izmene ukusa, smanjenje apetita, ponekad odbijanje hrane), te se u tim sluajevima preporuuje da-
vanje vitamina kao i obrada usne duplje.
Poremeaj sekrecije i motiliteta eludano-crevnog trakta este su pojave kod primene neuroleptika. Smanjenje ape-
tita, gaenje, bol u stomaku, povremeno povraanje, dijareja, ponekad se javljaju pri leenju rezerpinom, koji prema podacima
nekih autora poveava eludanu sekreciju. Neki opisuju eludana krvavljenja i perforacije ira na elucu kod primene rezerpi-
na. Mi smo, takoe, imali dva sluaja s perforacijom ira na elucu posle izvesnog vremena tretiranih rezerpinom.
Poznato je da Largactil smanjuje eludanu sekreciju i deluje nadraajno na sluzokou eluca, te na taj nain smanjuje
apetit, izaziva promenu i gubitak ukusa kao i peenje u epigastriumu. Profilaktino se preporuuje uzimanje svih ovih preparata
posle jela, kao i uzimanje veih koliina mleka posle toga.
Ako ove dispeptine pojave imaju stalan karakter, radi smanjenja gaenja i bola u stomaku preporuuje se Extractum
Belladonae. Jak bol u stomaku, povraanje i dijareja dovoljni su pokazatelji za prekid terapije i prelaz na parenteralni nain uvo-
enja preparata.
Neki lekovi (Nozinan) stvaraju sklonost prema opstipaciji, te se preporuuju laksantivna sredstva i klizme po potrebi.
Pri leenju antidepresivima kod pojedinih bolesnika se smanjuje eludana kiselina, to se moe odraziti na varenje hrane kao i
na resopciju leka.
Kao retka komplikacija javlja se poremeaj isputanja mokrae, koja je uslovljena spazmom sfinktera i atonijom mokra-
ne beike. Preporuuju se termoior, kateterizacija i neka holinergina sredstva (acetilholin hlorid), kao i analeptici (cofein i dr).
Izuzetno retko uoava se komplikacija u vidu paralitinog ileusa, koji je u vezi sa lokalnim spazmom glatko muskulature
(Rumore, 1962). U takvim sluajevima preporuuje se ukidanje neuroleptika i primena napred navedenih holinerginih sredsta-
va, klistir i drugo.
U nekim sluajevima javlja se poremeaj ejakulacije izazvane blokadom adrenerginih mehanizama.
Neki navode u vegetativne pojave i poremeaj menstruacije, laktacije, kao i pojavu impotencije kod primene neuroleptika.
Sve ove vegetativne pojave su uglavnom kratkotrajne i, u veem broju sluajeva, ne predstavljaju opasnost.
Ponekad je psihoterapija dovoljna mera leenja.

NAA ISKUSTVA
Primenjujui visokodozni i niskodozni flufenazin (Moditen) u 47 psihotinih bolesnika, zapazili smo vegetativne pore-
meaje u 16 bolesnika ili 34%. Brojano zastupljenost je bila sledea: hipersalivacija 7, smetnje akomodacije 2, hipotenzija 2, ta-
hikardija 2, muka i povraanje 1, suva usta 1 i alergini ertem 1.
lspitivanjem Leponexa u 61 shizofrenog bolesnika, zabeleili smo vegetativne pojave u sledeem obliku i broju: hiper-
salivacija 14, opstipacija 5, tahikardija 7, hipotenzija 3.
U jednog mlaeg bolesnika s ispoljenim maninim sindromom, ordinirali smo drugog dana od prijema 600 mg Leponexa
i postigli zadovoljavajui uspeh u otklanjanju postojeeg psihopatolokog sadraja. Meutim, u istog bolesnika zapazili smo po-
javu ortostatske hipotenzije, koju smo uspeli da otklonimo zadravanjem bolesnika u postelji, aplikacijom Sympatola i smanje-
njem Leponexa na 300 mg. U jednog drugog bolesnika na dozi od 300 mg, Leponexa, pojavila se tahikardija (120 do 140 udara
u minuti), te smo morali da prekinemo lek i zamenimo ga drugim.
Kombinacijom Leponexa i Moditena-depo nali smo u 41 shizofrenog bolesnika sledee vegetativne pojave: hipersali-
vacija 9, opstipacija 5.
Primenom kombinovane terapije sedativnih neuroleptika (levomepromazin, hlorpromazin, tioridazin). sa flufenazinom
(Moditen) i antiparkinsonskim preparatom (Artane), u 89 hroninih i akutnih psihoza nismo zapazili nlikakve sekundarne pojave
i to, kako vegetativne, tako ni ekstrapiramidalne.
Primenom drugih neuroleptika zapazili smo este pojave hipotenzije, a naroito primenom Nozinana i Largactila, koje
smo otklanjali Sympatolom u kapljicama ili ampulama, zavisno od jaine iste.
Dalje smo zapazili da se ove vegetativne pojave mogu da jave u svako doba tretmana, ali najee na poetku. Kod
jednog bolesnika moe da se javi samo jedna ili vie vegetativnih pojava u isto vreme. Tako smo kod jednog pacijenta leenog
Leponexom zapazili u isto vreme pojavu tahikardije, hipersalivacije i opstipacije. Intenzitet vegetativnih pojava je razliit kako
kod bolesnika, tako i kod raznih neuroleptiika. Negde su one slabije a negde jae izraene.
Sve zabeleene vegetativne pojave otklanjali smo smanjenjem ili ukidanjem leka, dodatnom terapijom ili izmenom po-
stojee terapije.

Saetak
Neuroleptici i antidepresivi kao aktivne hemijske supstancije, pored otklanjanja psihopatolokog sadraja, izazivaju i
sporedne efekte u obliku vegetativnih pojava.
One mogu da budu zastupljene u lakem iil teem obliku, mogu da predstavljaju opasnost po ivot bolesnika, te je po-
eljno poznavanje istih.
Neke od njih su prolazne i beznaajne, za neke je potrebna dodatna terapija a kod nekih izmena postojee terapije,
smanjenje ili prekid ordinirane psihotropne supstancije.
Sigurno je da neki psihotropni lekovi daju vei a neki manji broj vegetativnih pojava.

Summary

142
 Neuroleptics and antidepressive therapy as well as active chemical supstances, besides removing the psychopatholo-
gical contents, provoke subordinate effects in the form of vegetative appearances.
They could be represented in the easier or heavier form, they might be dangerous for a patient. so it is desirable that
one should know them.
Some of them are passable and of no importance. For some, there is a need of additional therapy, and for some there
is a need of changing the therapy, reduction or cutting of the prescribred psychothropic supstances.

Literatura
1. Avruckij G. i sarad. Farmakoterapija psihiesnih zabolevanij, Moskva. 1974. str. 154-294.
2. Vitorovi M. Ptsihofarmakoterapija shizofrenih psihoza - Psihijatrija - Simpozij o
neurologiji i psihijatriji, Ljubljana 1989.
3. Ignjatovi B., Zbornik V Kongresa Nevrologov in Psihiatrov Jugoslavije - Ljubljana 1976. str. 143-146 i str. 147-150.
4. Milovanovi D. Klinika psihofarmakoterapija, Ljubljana 1972.
5. Mihovilovi M. Psihofarmakoterapija depresisvnih stanja Psihijatrija - Simpo-
zij o neurologiji i psihijatriji, Ljubljana 1969.
8. Raevskij K., Farmakologija neuroleptikov, Moskva 1976, str. 207-245.

143
UDRUENO DEJSTVO LEPONEXA I MODITENA DEPO U LEENJU
SHIZOFRENIH PSIHOZA

Boidar Ignjatovi
Na kombinaciju Leponexa i Moditena depo odluili smo se posle dueg prouavanja ova dva leka. Smatrali smo da bi
mogli da postignemo bolji efekat onda gde oni pojedinano nisu bili dovoljni. Znali smo da Moditen depo nije dovoljno efikasan
kod shizofrenih psihoza praenih nesanicom, agitacijom, psihomotornim nemirom, agresivnou i razdraljivou. Leponex je,
pak, u ovim sluajevima bio veoma zahvalan i brzo otklanjao gore navedene simptome, ali je njegov antipsihotiki efekat bio ne-
to slabiji. Leponex, kao jedan novi neuroleptik, u ovim sluajevima gde smo ranije dodavali sedativno neuroleptike /nozinan, lar,

Naa iskustva
Kombinaciju Leponexa i Noditena depo primenjivali smo i vrili ispitivanja kod 41 pacijenta, od 22 do 65 godina staro-
sti i sa trajanjem bolesti od 1 do 25 godina. 2 bolesnika su ispoljavala akutan, a 39 hronian tok bolesti. Ispitivanje smo obavljali
na odeljenju gde se preteno lee hronino shizofrene psihoze. Po starosnoj strukturi od 20 do 29 godina leeno je 8, od 30-39
godina 8, od 40-49 21, od 50-59 3, i od 60-69 1 bolesnik. Po trajanju bolesti zastupljenost je bila: do 1 godine 2, od 2-10 godina 13,
od 11 do 20 godina 16, i preko 20 godina 10 bolesnika. Po dijagnostikoj strukturi leenje se kretalo: 295.0/Sch.simplex/ 5, 295.1 /
Heberhronia/ 18, 295.2 /Katatonia/ 1. 295.3 /Sch. Paranoides/ 11, 295.7 /Meana Sch. Alika/ 1, i 295.9 /neodreena forma Sch/ 5 bo-
lesnika, Po duini trajanja luenja do 3 meseca je bilo 5, do 5 meseci 22, do 7 meseci 9 i preko 7 meseci 5 bolesnika.
Optimalne doze Leponexa, koje su se kretale od 100-600 mgr zastupljene su bile u ovom odnosu: na 100 mgr 1, na 150 mrg 3, na 200 mgr.
2, na 300 mgr 26, na 450 mgr 1, na 500 mgr 2 i na 600 mgr 6 bolesnika. Svi ovi pacijenti su bili pre toga na Moditenu depo, a naknadno smo uve-
li i Leponex ili je pak najpre uveden Leponex a posle i Moditen depo. U toku leenja smo otpustili 13 a zadrali na bolniko leenje 28 bolesnika.

Sporedni efekti ispitivanja

Pospanost smo zapazili kod 9 bolesnika i to odmah na poetku leenja na dozi od 300 mgr, ali je kratko trajala, od 1
do 3 dana. Hiper-salivaciju takoe kod 9 bolesnika na dozi od 300 mgr, ali je nije bilo na 150 mgr. Kod 4 bolesnika zabele-
ili smo lak zamor i malaksalost i kod 5 opstipaciju. Ekstrapiramidne pojave, kao i druge uporedne efekte koje smo rani-
je zabeleili primenom Moditena depo od 25 mgr na 25-30 dana /nesanica 25, akatizija 4, tremor ruku 2, rigor 2 i okulogir-
ne krize 1/ sada nismo nali iako je doza Moditena depo i u ovom sluaju uz Leponex bila ista i u istom razmaku ordinirana.

Boidar Ignjatovi, neuropsihijatar, ef odeljenja F u Neuropsihijatrijskoj bolnici, Vrac

Rezultati leenja
Rezultati leenja Leponexa i Moditenom depo prikazaemo na sledeoj tabeli:
Tabela 1.
Rezultati leenja Broj pacijenata Procenat

+++ 32 78,o%
++ 9 22,0%
0 0%
UKUPNO 41 100 %
Radi boljeg pregleda i uporeenja prikazaemo nae rezultate u sva tri sluaja:
Rezultati leenja shizofrenih psihoza samo Moditenom depo izraeni u procentima znatno poboljanje 53%, delimino po-
boljanje 21,3%, neuspeh 25,7%
Rezultati leenja shizofrenih psihoza samo Leponexom: znatno poboljanje 57,4%, delimino poboljanje 34,5%, neupseh 8,1%
Rezultati leenja shizofrenih psihoza kombinacijom Leponexa i Moditena depo i znatno poboljanje 78,0%, delimino po-
boljanje 22,0% i neuspeh 0%.
Iz gore navedenih rezultata jasno se vidi da smo najbolje uspehe postigli primenom kombinacije Leponexa i Moditena
depo.
Najbolji uspeh smo i ovde postigli u najveem broju sluajeva na dozi od 300 mgr Leponexa, a kod nekih tek na dozi
od 600 mgr. Mnogi bolesnici koji su ranije leeni i pokazivali neuspeh na prethodnoj terapiji sada su se nekako ponovo vratili u
ivot, ak smo neke i otpustili kui i sa uspehom nastavili i vanbolniko leenje.
Brzo i sigurno smo pri prijemu novih bolesnika ili pri posmatranju psihikog stanja hospitalnih bolesnika, otklanjali ne-
sanicu, psihomotorni nemir, agitaciju, agresivnost i paranoidno-halucinatorni sadraj. Zamenom Leponexa nekim od sedativnih
neuroleptika esto je dolazilo do pogoranja klinike slike.
Na sledeoj tabeli emo prikazati i rezultate leenja po dijagnostikoj strukturi:

144
 Tabela 2.

ifra bolesti Dijagnoza +++ ++

295.0 Sch.simplex 3 2 -
295.1 Hebephrenia 14 4 -
295.2 Katatonia 1 - -
295.3 Sch.paranoides 9 2 -
295.7 Meana Sch.slika 1 - -
295.3 Neodreena forma Sch 4 1 -
Svega: 32 9 0
Nae objanjenje: +++ = znatno poboljanje
++ = delimino poboljanje
= neuspeh.

Zakljuak
1. Kombinovanom terapijom Leponexa i Moditena depo postigli smo bolje rezultate nego pojedinanom upotrebom.
2. Pored odlinog sedativnog i umerenog hipnotikog pojaali smo antipsihotino dejstvo Leponexa dodavanjem Moditena
depo.
3. Postigli smo uspeh ne samo u otklanjanju nesanice, poihomotornog nemira, agitacije, napetosti, agresivnosti ve i u
boljem i brem otklanjanju paranoidno~halucnatornog sadraja, kao i poboljanju volje, interesovanja i raspoloenja.
4. Tamo gde nismo postigli eljene rezultate na dozi Leponexa od 300 mgr uz Moditen depo, uspeli smo da to popravimo
poveanjem doze od 600 mgr.
5. Ekstrapiramidne pojave koje smo zapazili primenom Moditena depo bez kombinacije sa Leponexom, sada se nisu po-
javile ni u jednom obliku.

Rezime
Autor je ispitivao kombinovano dejstvo Leponexa i Moditena depo kod akutnh /2/ 1 hroninh /39/ shizofrenih psihoza u
vremenu od 3 do 8 meseci. Leponex je ordiniran u dozi od 100 do 600 nage dnevno, a Moditen depo od 25 mgr na 25-
30 dana parenteralno.
Pojaavanjem antpsihotkog uz odlino sedativno i umereno hipnotiko dejstvo postigli smo bolje rezultate u otkla-
njanju paranoidno halucinatornog sadraja, nesanice, psihomotornog nemira agitacije, napetosti, agresivnosti, kao i po-
boljanje volje, interesovanja i raspoloenja.
Rezultati leenja su bolji nego kod pojedinane primene Leponexa ili Moditena depo, a u procentima izgledaju ovako:
+++ = 78,0% ++ = 22,0% i = 0.
Za razliku od ekstrapiramidnih pojava koje smo registrovali primenom samo Moditena depo ovde ih nismo zapazili.
Zbog toga kombinaciju Leponexa i Moditena depo preporuujemo u leenju svih formi shizofrenija.

Heuropsychiatric Hospital, Vrac, Yugoslavia

145
THE COMBINED ACTION OF LEPOHEX AND MODITLEN DEPO IN
TREATING SCHIZOPHREHIC PSYCHOSES

Boidar Ignjatovi

Summary
The author investigated the combine action of Leponex and Moditen depo in acute /2/ and Chronic /39/ schizophre-
nic psychoses during 3 to 8 months. Leponex was administered in dosages from 100 to 600 mg per day, and Moditen depo of
25 mg parenterally per 25 to 30 days.
We reached much better results by amplification of the antipsychotic action in the same time when we had excellent
sedntive and moderate hypnotic affects in removing psychopatological content as they are in: insomnia, agitation, routessness,
tension, aggressive behavior, paranoid-hallucinatory change, with improvement of the will, interesting and the mood.
The results of the treatment are much better than in the case of the single application of Leponex or Moditen depo. These
results presented in percents look like this: +++ = 78,0%, ++ 22.0% and =0.
The registered extrapyramidal phenomena, with application of Moditen depo only, we did riot notice.
Because of the above mentioned results we recommend the combination of Leponex and Moditen depo in treating all forms
of a schizophrenia.

Literatura
1. Angst J.; Methodology for the Clinical Testing of Psychotropic Agents, Sumposium on the methodology of the pharmaco-
logical and trials of psychotropic drugs, Moscow, 1974.23-35.- 2. Avrutky G. Y., Zaitsev S.G., Magalif A.Y., Hofman D. Y. :Criteria
for Comparative Evaluation of Neuroleptic Drugs as Appied in a Study of the effect of Leponex in Schizophrenic Patients,
Symposium, Moscow, 1974, 49-63. 3. Bukowczyk A. Clinical Invesitigations of Clozapine in Schizophrenia, Symposium,
Moscow, 1974, 115-127. 4. Bohaek, N., Principi prolongirane psihofarmakoterapije shizofrenih psihoza /zneenje leenja depo
neurolepticima/ u Novosti 1, Krka, 1972:str.85-88.-5. Fouks L. , IV me Congres Mondial de psychiatrie, Madrid 5-11 Septembra
1966. Edition squibb et cons. 6. Freeman H., Symposium on long-acting phenotiazines, Dublin, 1969. 7. Frank L. ,International
Drug therapy, Newsletter, Baltimore, 1970. Volume V.Number4. 8.Hippius H. Matussek N.: Clinical and Biochemical Findings with
Clozapine,Symposium, Moscow, 1974,65-70.-9. Imlah N., Symposium on long-acting phenotinzines, Dublin, 1969.- 10.Lange
E., Konig L., Kuhne G.,Liefke T.; Experience with Leponex in Clinical Practice, Symposium, Moscow,1974,109-113.- 11.Lokar L.
Upotreba Flufenazin decanoata u socijalnim zavodima, u Novosti 1, Krka, 1972.str.95-98.- 12. Milovanovi D. Klinika psihofarma-
kologija. Izdanje Lek, Ljubljana, 1972.-13, Nevgorova T.A. Galperina L. E. , Obrachevskaya V.D., Verhovskaya T.V. :The Trentmant
of Schizophrenic Patients with Leponex, Symposium, Moscow, 1974,101-108.-14. Nabney J., Symposium on long-acting phe-
notiazines, Dublin, 1969.-15. Petrovi D., Sedmak T.:Psihofarmakoterapija dugo 1eenih psihoza shizofrenog tipa, u Anali zavoda
za mentalno zdravlje, Beograd, 1974, god.6, br.1,29-39.-16 Vencovsky E., Fischer-Cornelseen K.: Results of a Double-blind Clinical
Study Comparing the efficacy of Clozapine and Chlorpromazine, Symposium Moscow, 1974, 93-100. -17. Vitorovi, M., Naa
iskustva i na stav u leeenju depo-flufenazinom, u Novosti 1, Krka, 1972.str.89-93.

146
NAA ZAPAANJA U LEENJU SHIZOPHRENIA LEPONEXOM

Boidar Ignjatovi
Kao najefikasniji lekovi u leenju shizofrenije u zadnjih deset godina meu psihofarmacima bili su neuroleptici, a njihov an-
tipsihotiki efekat je bio zasnovan na definiciji izraza neuroleptiki, Tako su kliniari skretali panju i dokazivali da bi neki lek
mogao da bude efikasniji samo onda ako bi prouzrokovao i ekstrapiramidne sporedne efekte. Meutim, situacij se menja sa
otkriem Leponexa. Leponex ima isti terapeutski efekat kao i klasini neuroleptici pri klinikoj upotrebi, a razlikuje se od njih
samo u tome to ne utie na ekstrapiramidni sistem, odnosno ne daje ekstrapiramidne pojave u eksperimentu na ivotinjama ili
primenom na ljudima. Po hemijskoj strukturi Leponex je blizak klasinim neurolepticima.

Klasini neuroleptici koji pripadaju grupama fanotijazina i butirofenona imaju blokirajui efekat na receptore dopamine u CNS.
Leponex takoe utie na dopaminergine neurone u CNS na taj nain to dovodi do porasta homovanilske kiseline /HVA/ u mozgu tj.
Utie kao i klasini neuroleptici na metabolizam dopamine, ali u isto vreme suprotno njima uestvuje i na metabolizam norepinefrina.
Blagodarei ovim biohemijskim, farmakolokim i neurofiziolokim istraivanjima na ivotinja-
ma i ljudima danas ne zna da domaminergini neuroni ne samo da postoje u ekstrapiramidnom siste-
mu nego takoe u limbikom i eonom renju CNS, to bi moglo biti razlogom za antipsihotino delovanje.

Naa iskustva
Leponex smo ispitivali kod 61 shizofrenog bolesnika od 17 do 69 godina starosti i sa trajanjem bo-
lesti od 1 do 30 godina. Kod 2 bolesnika tok je bio akutan, a kod 59 hronian. Lek smo primenjiva-
li kod hospitalnih i ekstrahospitalnih bolesnika. Broj bolesnika leenih po dijagnostikoj strukturi izgledao je ovako:
295.0/Sch. Simplex/ 6.295.1/Hebephrenia/21.295.3/Sch.paranoides/18.295.9/Neodreena forma Sch./ 16.
Na prethodnoj terapiji ovi bolesnici nisu pokazivali neki naroiti uspeh. Leponex smo ordinirali odmah, neposredno posle
prekida prethodne terapije, tako da nismo pravili pauzu od 7 dana koju prave neki autori zbog ispiranja.
Po duini trajanja Leponexa smo primenjivali kod 26 do 3 meseca, kod 23 do 5 meseci, kod 7 do 7 meseci i kod 5 bole-
snika preko 7 meseca. Od ukupnih broja 61 leenih, otpustili smo 24, a u bolnici nastavili leenje kod ostalih 37 bolesnika.
Optimalne doze su se kretale od 75 mgr do 600 mgr dnevno, a u odnosu prema broju bolesnika i izgledale su ovako: 2 bolesnika
po 75 mgr, 4 bolesnika po 150 mgr, 40 bolesnika po 300 mgr, 7 bolesnika po 450 mgr i 8 bolesnika po 600 mgr dnevno. Visina
optimalne doze kretala se u zavisnosti od prethodne terapije, stanja remisije ili egzacerbacije procesa, somatskog zdravlja kao i
odgovarajueg uspeha pri primeni iste.
U toku tretmana nismo zapazili da se paranteralna primena pokazala efikasnijom od oralne.
Sporedni efekti ispitivanja
Nuspojave koje smo primetili izgledale su po obliku i broju ovako: hipersalivacija 14, pospanost 7, opstipacija 5, lak zamor 3,
tahikardija 2, hipotenzija 3 i tremor 1.
Ovi sporedni efekti imaju i neke svoje posebne karakteristike koje smo mi u toku ispitivanja zapazili.
Mogu da se jave u svako vreme tretmana, ali najee na poetku.
Kod jednog istog bolesnika moe da se javi samo jedna od gore navedenih nuspojava ili vie njih u isto vreme ili u razliito
vreme tretmana. Kod dva bolesnika smo morali da prekinemo zapoetu terapiju Leponexom zbog nagle pojave vie nuspojava
odmah na poetku leenja / tahikardija 120/140, hipersalivacija, pospanost, lak zamor i opstipacija/.
Postoje razlike i u intezitetu nuspojava, tako to su kod nekih bolesnika jae, a kod drugih slabije izraene.
Isto tako i doza leka ima nekog znaaja u pojavi istih. Na dozi od 300 mgr bilo je najvie zabeleenih sporednih efekata, a od
njih je najbrojnija bila hipersalivacija koja je ne samo iezavala smanjenjem leka ve negde ak i poveanjem na 600 mgr. Kod
drugih, pak, na dozi od 600 mgr nije bilo nikakvih nuspojava.
Sve gore navedene sporedne efekte uspevali smo da otklonimo bilo smanjenjem, bilo ukidanjem leka.
Rezultati leenja
Pratei tok leenja i sumirajui rezultate na osnovu nae subjektivne procenemogli smo da konstatujemo da je povlaenja
psihopatolokog sadraja dolo na razliite naine.
Najbojle rezultate kod najveeg broja bolesnika postigli smo na dozi od 300 mgr dnevno. Delimian uspeh na 75 odnosno
150 mgr, a poveanjem doze do 600 mgr dnevno ak i znatno poboljanje.
Kod hroninih bolesnika koji su dugo bili rezistentni na svu prethodnu terapiju i nisu pokazivali nade za neko poboljanje ili
izleenje postigli smo dobre rezultate kod nekih na 300 mgr, ali jo bolje uspeh kod vie njih na 600 mgr dnevno.
Odmah na poetku leenja zapazili smo brzo i efektno dejstvo u otklanjanju nesanice, napetosti, psihomotornog nemira i
agresivnosti, a neto sporije u potiskivanju paranoidno halucinatornog sadraja, razdraljivosti, anksioznosti, emocionalne tu-
posti, autizma i odbojnosti prema radu.
Zamena Leponexa prethodnom ili nekom drugom terapijom dovodila je esto do izmene klinike slike u smislu pogoranja
bolesti.
Radi boljeg pregleda na sledeoj tabeli prikazaemo leenja Leponexom.

147
 Tabela 1.

Rezultati leenja Broj pacijenata Procenat

+++ 35 57,4%
++ 21 34,5%
5 8,1%
Ukupno 61 100%
Rezultate leenja po dijagnostikoj strukturi prikazujemo na sledeoj tabeli:

Tabela 2.

Sifra bolesti Dijagnoza +++ ++

295.0 Sch.simplex 4 3
295.1 hebephrenia 11 8 2
295.3 Sch.paranoides 12 3 2
295.9 Neodreena forma 8 7 1
Sch.
Svega 35 21 5

Zakljuak
Leponex ili Clozapin /generiko ime/ moglo bi se rei da je opravdao nae poverenje u leenju shizofrenih psihoza.
Njegovo snano antipsihotino, odlino sedativno i sa poveanjem doze negde manje negde vie ispoljeno hipnotiko dej-
stvo stavljaju ga u red moglo bi se rei isperd Nozinana i Largnactila.
S obzirom da ne daje skoro nikakve ili vrlo retko blage ekstrapiramidne pojave pogodan je za leenje bolnikih i vanbolni-
kih pacijenata.
Naroito je pogodan za leenje onih bolesnika koji pri prijemu ili za vreme egzacerbacije procesa ispoljavaju nesanicu, psi-
homotrni nemir, napetost, agresivnost i paranoidno-halucinatorni sadraj.
Vegetativne smetnje koje izaziva ree se javljaju, kratkog su trajanja i brzo nestaju smanjenjem doze leka.
Delimino poboljanje ili neuspeh koji se ponekad ispoljavaju kod malih doza leka, mogu se poboljati poveanjem iste.
Rezime
Leponex smo primenjivali kod aakutnih /2/ i hroninih /59/ shizofrenih psihoza u vremenu od 3 do 8 meseci i to kako kod hos-
pitalnih tako i kod vanhospitalnih pacijenata. Ordinirali smo ga oralno i parenteralno u dozi od 75 do 600 mgr dnevno.
U toku ispitivanja zabeleeli smo sledee rezultate: znatno poboljanje kod 35 ili 57,4%, delimino poboljanje kod 21 ili 34,5%
i neuspeh kod 5 pacijenata ili 8,1%. Kod dva bolesnika morali smo da prekinemo leenje zbog pojave tahikardije /120-140/ i nekih
drugih vegetativnih smetnji kod istog bolesnika.
Nae objanjenje: +++ = znatno poboljanje
++ = delimino poboljanje
= neuspeh.
S obzirom da poseduje brzo i dugotrajno sedativno, snano antipsihotino i slabije ili hipnotiko dejstvo naroito sa pove-
anjem doze, smatramo ga pogodnim u otklanjanju nesanice, psihomotornog nemira, napetosti, agresivnosti i paranoidno-ha-
lucinatornog sadraja.
Sporedni efekti ispitivanja a naroito ekstrapiramidne pojave ako se pojave, mada ree, lako se otklanjaju smanjenjem doze,
a ponekad i ukidanjem leka.

Neuropsychiatric hospital, Vrac, Yugoslavia

148
OUR OBSERVATIONS IN TREATING SCHIZOPHRENIC BY LEPONEX

Boidar Ignjatovi
We were applyinc Leponex in acute /2/ and chronic /39/ acidzophronic psychoses during 3 to 8 months. Both inpatients and
outopatients were treated. Leponex was administrared orally and parenterally in dosages from 75 to 600 mg per day.
In the course of investigations we noted the following results: notable improvement in 35 patients or 57 percent, partial im-
provement in 21 or 34,5% and unsuccess in 5 patients or 8,15. In cases of 2 patients only-the treatment was interrupted due to
the appearance of tachicardia /120-140/.
Having in view thet Leponcx has quick and long-acting sedative effects, strong antipsychtic action and weaker or stronger
hypnotic properties, especially with higher doseges - we consider that Leponex is favourable for healing incomnia, restlessne-
ss, tension, aggressive behavior and paranoid-hallucinatory contents.
Side effects in this study, and especially oxtrapyramidal effects, are rare and if they appear they to be removed by lowering
the dosages or sometimes by stopping the administration of Leponex.
Literatura
1.Angst J.: Methodology for the Clinical Testing of Psychotropic Agents, Symposium on the methodology of the pharma-
cological and trials of psychotropic drugs, Moscow, 1974,23-35.2.Avrutky G.Y. Zaitsev S.G., Magalif A.Y., Holman D.Y. :Criteria
for Comparative Evaluation of Neuroloptic Drugs as Appied in a Study of the Effect of Leponec in Schizpphrenic Patients,
Symposium, Moscow, 1974,49-63. 3.Bukowczyk A.Clinical Investigations of Clozapine in Schizophrenia, Symposium, Moscow,
1974,115-127.-4 Hippius 11.,Matussek N.:Clinical and Biochemical Findings with Clozapine, Symposium, Moscow, 1974, 65-70.
5 Lange E.,Konig L.,Kuhne.G.,Liefke T.; Experience with Leponex in Clinical Practice, Symposium, Moscow, 1974.109-113.-6
Milovanovi D.: Klinika psihofarmakologija. Izdanje Lek,Ljubljana,1972. 7.Nevsorova T. A. Galperina L. E. ,Obrachevskaua V. D.
Verhovskaya. T. V. : The Treatment of Schizophrenic Patients with Leponex, Symposium, Moscow, 1974,101-108.-8 Petrovi
D. Sedmak T.: Psihofarmakoterapija dugo leenih psihoza shizofrenog tips, u Anali zavoda za mentalno zdravlje -Beograd, 1974
god.6,br.1, 29-39.-9 Vencovsky E.,Fischer-Cornelssen K.: Results of a Double-blind Clinical Study Comparing the Efficacu of
Clozapine and Chlorpromazine, Symposium Moscow, 1974, 93-100.

149
Sadraj / Table of Contents

5 Agoraphobia with panic disorder - family psychopharmacotherapy by paroxetin

10 Acamprosate for out-patient alcohol dependence treatment
16 Outpatient psychiatrist activities of consultations in diagnosting process and treatment of
psychosomatic disorders
23 Possible adverse effects in the treatment of agoraphobia with valproic acid and natrium valproate-
our one year experiences
27 The efficacy of depression treatment with milnacipran (a six- month experience)
35 Rivastigmine efficacy on behavioral and psychological symptoms of alzheimers disease- findings from
a 12-months out- patients study.
41 Chronificated agoraphobia with panic disorder monitoring during one year interval and assumption of
comorbidity with depression uprise
47 Psychopharmacotherapy or psychotherapy of anxiety disorders- one year results
53 Differential diagnostics of panic disorder and following treatment at the psychiatric clinic - our 1 years
experience
63 Is combination of psychopharmacotherapy and psychotherapy effective at treatment of agoraphobia
wiht a panic disorder?
66 Pharmacoeconomics of the treatment of agoraphobia with panic disorder
67 The efficacy of depression treatment with M1lnacipran (a six- month experience)
70 Crises periods in the treatment of alcoholism addiction syndrom in psychiatric medical office
75 Agoraphobia with panic disorder family psychopharmacotherapy by paroxetin
79 Treatment of somatoform and psychosomatic disorders at outpatient psychiatric center
84 Cognitive and behavioral psychotherapy of specific phobia- casuistic
86 Pharmacoeconomics of the treatment of agoraphobia with panic disorder
87 Pharmacological treatment of late-life depression
93 The efficacy of depression treatment with milnacipran
98 The risk of suicide in the geriatric patients community
103 The quality of life in patients with dementia of Alzheimers type living in old peoples homes and
nursing homes
108 Comparison of galantamine and rivastigmin effects - 12-month study
112 Pouitie mobilnho telefnu ako pomocky pri panickom zchvate (use of mobile telephone during
panic attack)

150
118 Treatment of somatoform and psychosomatic disorders at outpatient psychiatric center
123 Moditen u leenju shizofrenih psihoza
125 The Moditen in treating schizophrenic psychoses
126 Ekstrapiramidalne pojave kod primene neuroleptika njihov znaaj i leenje
127 Extrapyramidal phenomena in the application of neuroleptics their importance and healing
128 Penfluridol u leenju hroninih shizofrenih psihoza
129 Penfluridol in treating the schizophrenic chronic psychoses
130 Znaaj visokih i niskih doza neuroleptika u leenju shizofrenih psihoza
131 The importance of high and low doses of neuroleptics in treatment schizophrenic psychoses
132 racionalna upotreba psihofarmaka
134 Znaaj ekstrapiramidalnih pojava kod primene psihofarmaka
136 Kliniki aspekti hroninih neuroleptikih pojava
137 Dileme pri upotrebi psihofarmaka
139 Dihydroergotamin- metansulfonat (ditamin) u leenju glavobolja
140 Dihydroergotamine-metha-nesulfonate (ditamin) in treating headache
141 Vegetativni poremeaji pri upotrebi psihotropnih lekova
144 Udrueno dejstvo leponexa i moditena depo u leenju shizofrenih psihoza
146 The combined action of lepohex and moditlen depo in treating schizophrehic psychoses
147 Naa zapaanja u leenju shizophrenia leponexom
149 Our observations in treating schizophrenic by leponex

151
 Ignjatovii - 40 godina u psihijatriji

Autor
Dr Milan Ignjatovi

Prelom
Zorica Mujkovi

Dizajn
Aleksandar Pasku
www.freakinc.rs

Obrada skenova
Kristina Ili

Tehnika podrka
Bratislava Cvetkovi Ili

tampa
Gama Studio, Beograd

Tira
100 komada

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