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SCHIZOPHRENIA

Dr. W.M ROAN, DPM(Lond.), SpKJ(K)

PERSPECTIVE HISTORY OF THE


DISCOVERY OF SCHIZOPHRENIA

MOREL(1860) : DMENCE PRCOCE


EMIL KRAEPELIN(1899) : DEMENTIA
PRAECOX: DETERIORASI KEPRIBADIAN
(personality deterioration)

HECKER(1871): HEBEFRENIA (Silly Deter.)


KAHLBAUM(1874): KATATONIA (catatonia)
JASPERS(1910): TAK DPT DI-EMPATI
(cannot be empathized)

HISTORY (1)

EUGEN BLEULER(1911):
SCHIZOPHRENIE
GEJALA KARDINAL (Cardinal symptoms)
GEJALA AKSESORIS (accessory symptoms)

ADOLPH MEYER(1920): REAKSI ORANG THD


KEGAGALAN MENGATASI MASALAH HIDUP (human

reactions towards failures in coping with life)

Bleulers Concept of schizophrenia (1)


Cardinal Symptomen
Der Autismus (autism)
Die Aufmerksamkeit (attention)
Der Wille (volition)
Die Person (The person)
Die Schizophrene Demenz (dementia schiz)

Bleulers Concept

(2)

Akzessorischen symptomen (accessory symptoms)


Wahrnehmung (perception of the 5 senses)
Wahnideen (delusions)
Gedchtnisstorungan (disturbances of thought)
Depersonalisation (depersonalization)
Sprache und Schrift (speech & language)
Krperliche Symptome (bodily symptoms)
Die Katatone Symptome (catatonia)
Akut Syndrome (acute syndrome)

HISTORY (2)

RMKE(1935): PRAECOX GEVOEL


Barrier between doctor pt relationship

KURT SCHNEIDER(1939): FIRST RANK


SYMPTOMS
SPECIFIC HALLUCINATIONS
ECHO DE LA PANSE (THOUGHT-ECHO,
-SONORIZATION, GEDANKENLAUTWERDEN,
AUDIBLE THOUGHT)
PT BEING COMMENTED IN THE THIRD PERSON
PASSING COMMENTARIES ON PT'S BEHAVIORS

HISTORY (3)
DISTURBANCE OF EGO BOUNDARY

SOMATIC PASSIVITY FEELINGS


THOUGHT WITHDRAWAL / INSERTION / BROADCAST
MADE FEELINGS
MADE IMPULSES
MADE VOLITIONAL ACTS
DELUSIONAL PERCEPTION (PRIMARY DELUS.)

KUSUMANTO SETYONEGORO(1966)
6 A: DISTURBANCES OF ATTENTION,
AFFECT, AUTISM, ASSOCIATION,
AMBIVALENCE, ABULIA

SEJARAH (Sambungan IV)


LAING (1960s): ANTIPSYCHIATRY

AGAINST

THE LABELLING OF SCHIZOPHRENIA


ECT
HOSPITALIZATION
CHILDREN BEING DRUGGED

PATIENTS ARE NORMAL, THE SOCIETY IS


ILL
PTS, STAFF & DOCTORS ARE EQUAL

WHO ICD-10
DIAGNOSTIC CRITERIA
WHO ICD-10 = PPDGJ-III

THOUGHT ECHO , THOUGHT-INSERTION,-WITHDRAWAL,


-BROADCASTS
DILUSION OF CONTROL
HALLUCINATORY VOICES
WAHAM MENETAP
HALUSINASI MENETAP
THOUGHT BLOCKING
CATATONIA
NEGATIVE SYMPTOMS
PERSONALITY CHANGE

SCHIZOPHRENIA
PERSPECTIVE & PRACTICAL REVIEW
POSITIVE SYMPTOMS
NEGATIVE SYMPTOMS
COGNITIVE FUNCTION DISTURBANCES
AFFECTIVE LIFE DISTURBANCES
PSYCHOMOTOR DISTURBANCES

EXTRAPYRAMIDAL SYMPTOMS (-)

VEGETATIVE FUNCTIONS: SLEEP, EAT, SEX


QUALITY OF LIFE

POSITIVE SYMPTOMS OF
SCHIZOPHRENIA
Gg bentuk pikir, asosiasi longgar (loosening of
association)
Tingkah laku kacau, keluyuran (disorganized &
erratic behaviour, vagabondage)
Afek tak serasi, bermusuhan (incongruent affect,
hostile)
Waham, megalomania, w.-kejar (delusion,
megalomania, persecutory d.)
Halusinasi & perilaku penyerta (hallucinations &
subsequent behaviours)

NEGATIVE SYMPTOMS OF
SCHIZOPHRENIA
Tuna/Miskin pikir & wicara (Poverty of thought
and speech)
Gg kehendak (impaired volition, apathy)
Afek tumpul (blunt affect & anhedonia)
Penarikan diri (Social withdrawal)
Hubungan dr-ps kurang hangat (Poor rapport)
Sulit berpikir abstrak & stereotipi (Abstract
thinking & stereotipy)

Cognitive Functions
daya perhatian (attention)
daya ingat (memory)
daya tanggap (perception)
daya cakap & bahasa (speech & language)
daya belajar & pembelajaran (learning)
daya komunikasi (communication)
fungsi exekutif (executive functions)

EXECUTIVE FUNCTIONS
MEMORI & PERSEPSI (memory & perceptions)

MENYIMPAN, MENGATUR, PERBARUI, MENGGUNAKAN


INFORMASI (retention, organization, update, information)
MEMILIH RESPONS YG TEPAT, MEREDAM YG TIDAK
TEPAT (select the appropriate & discard the useless response)
MEMBUAT RENCANA, MENYELESAIKAN MASALAH
(planning, executing)

DEFISIT (Deficits):

GEJALA NEGATIF: TAK ADA SPONTANITAS, KURANG


MOTIVASI, ASOSIAL (Negative symptoms: lack initiatives,
unmotivated, asocial)

POOR SELECTIVE ATTENTION OR FILTERING

HALLUCINATIONS, IDEAS OF REFERENCE

Gejala afektif skizofrenia


(Affective symptoms of schizophrenia)
Fase skizofrenik (schizophrenic phase):

depresi / mania (depression / mania)


cemas / panik, (anxiety / panic)
obsesi / kompulsi, (obsession / compulsion)
histerik, (hysterical)
fobia akibat halusinasi atau waham (phobia due to
hallucinations / delusions)

Fase kronik (chronic phase)

gejala negatif, menarik diri, autistik, malas, tak mau ganti


pakaian, kotor (negative symptoms: withdrawn, autistic, lack of
initiatives, avoid bathing, unkempt, no change of clothing)

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PSYCHOMOTOR DISTURBANCES
EXTRAPYRAMIDAL DISTURBANCES

AKINESIA, BRADYKINESIA (Akinesia, bradykinesia)


AKATHISIA (Akathisia)
TREMOR, RABBIT TREMOR
PARKINSONISM
OCULOGIRIC CRISIS (Oculogyric crisis)
DISTONIA, HEMIBALISMUS, SINDROM PISA (dystonia,
hemibalism, pisa syndr)
CHOREO-ATHETOSIS (choreo-athetotic movement dist.)
TARDIVE DYSKINESIA (Tardive dyskinesia)

TARDIVE
DYSKINESIA

DEVELOPMENTAL HISTORY OF
SCHIZOPHRENIA THERAPY
1952 OVERCOME POSITIVE SYMPTOMS
1980 ALLEVIATE NEGATIVE SYMPTOMS
1990 IMPROVE COGNITIVE DYSFUNCTIONS
1995 PREVENT AFFECTIVE DISTURBANCES
1997 THE CHOICE OF DRUGS, COMFORTABLE
NO SIDE EFFECTS
2000 MAINTAIN & IMPROVE QUALITY OF
LIFE

ATYPICAL ANTIPSYCHOTIC DRUGS


NOVEL
Receptor profile*

A N T I P S Y CH O T I CS
DRUG
Recommended dose Pharmaceut. Co
(Waddington)
(mg/day)**
Amisulpride D2/3, D1, D2
200 - 800 (50 - 1200) Sanofi - Synthelabo
Clozapine 5HT2, D, M, H1
200 - 450 (50 - 900) Novartis
Olanzapine 5HT2, D, M, H
10 (5 - 20)
Ely Lilly
Quetiapine 5HT2, D2, H1
150 - 750
Astra Zeneca
Risperidone 5HT2, D, H1
4 - 6 (1 - 16)
Janssens
Sertindole 5HT, D,
12 - 20 (4 - 24) Lundbeck
Ziprasidone 5HT2, D2, 5HT1A, M1,
40 - 160
Pfizer
Zotepine
5HT2, D1,2 H1, M
100 - 300 (50 - 450) Rhone - Poulenc Rorer

D : Dopamin, adrenergik, M : Muscarinic, H : Histamine, 5HT : Serotonin


* ) Listed in order of descending affinity
**) Doses in general correspond to the recommendations of the manufacturer.
Doses listed in parentheses represent extremes sometimes justified in individual patients.

Chemical Structures of Olanzapine and Other


Antipsychotic Agents
1. Multi-Acting Receptor Targeted Antipsychotics (MARTA)
CH
3
N

C3
H

OH
N

C
l

Clozapine

CH
3

Seroqel

Olanzapine

2. Serotonin: Dopamine Antagonists (SDA)


N

3. Dopamine - 2 Antagonist

H
N

CH 3

H
O

Cl

N
N

H
N

Sertindole

Risperidone

C
l

N
O

Haloperid
ol

Olanzapine has eliminated the halogen (Cl) from the clozapine molecule,
a potentially reactive metabolite

Receptor pharmacology of
atypical antipsychotics
Haloperidol

Clozapine

Olanzapine

Quetiapine

Risperidone

Sertindole

Ziprasidone

Zotepine

D1
D2
D4
5HT2A
5HT2C
Musc
1
2
H1

INDICATIONS OF NEUROLEPTIC
ADMINISTRATION
FIRST LINE TREATMENT FOR VARIOUS SCHIZOPHRENIA
& OTHER PSYCHOTIC CONDITIONS
RESISTENT SCHIZOPHRENIA TOWARDS DRUGS &
HANDICAPPED
PSYCHOTIC DITURBANCES WITH AFFECTIVE ELEMENTS
DEPRESSIVE / MANIC
ORGANIC PSYCHOTIC DISORDERS
PSYCHOTIC DISORDERS WITH COGNITIVE
DYSFUNCTIONS
OVERCOME POSITIVE SYMPTOMS
IMPROVE NEGATIVE SYMPTOMS
AUTISTIC SPECTRUM DISORDERS
OBSESSIVE COMPULSIVE DISORDERS
SCHOOL PHOBIA IN CHILDREN

SIDE EFFECTS OF ATYPICALS


WEIGHT GAIN
SEXUAL DYSFUNCTIONS
LOWERED CONVULSIVE THRESHOLD
HYPOTENSION / HYPERTENSION
AGRANULOCYTOSIS (ESP. CLOZAPINE)
HIPERPROLACTINEMIA, AMENORRHOEA
HYPERGLYCEMIA, DM, KETOACIDOSIS,
COMA

(CONT)
PR & QTc, QRS, PROLONGATION, ST
FLATTENING/NOTCHING T-WAVES, EMERGENCE OF
U-WAVES (FOR ZYPRASIDONE, OLANZ, RISP.)

INCREASE CREATININ PHOSPHOKINASE


SOMNOLENT (FOR CLOZAPINE) / INSOMNIA
SEVERE HEADACHE / AGITATED
DRY MOUTH
INCREASED ALT & AST

SIDE EFFECTS DIFFERENCES AMONG


NEUROLEPTICS
EXTRAPYRAMIDAL SIDE EFFECTS:

RISP > ZIPRA/OLAN > QUET

PROLACTINEMIA, AMENORRHOEA:

RISP > ZIPRA/OLAN > QUET

WEIGHT GAIN:

OLAN > QUET/RISP > ZIPRA

GENETICS & DISEASES


Single-gene mutations & rare diseases
(Mendelian inheritance)
Cystic fibrosis
(CFTR gene)
Rare inheritance
(high penetrance)
Inheritance: autosomal recessive
Location: chromosome 7 (7q31)
Mutation: deletion of 3 bp at codon 508 accounts to
70% of mutations

Huntingtons disease
Inheritance: autosomal dominant
Location: Chromosome 4 (4p16.3)
Mutation: cytosine/adenine/guanine repeat>35x

Gene polymorphisms and common disease


susceptibility - some examples
(polygenic; complex inheritance)

Common late-onset Alzheimer's disease


Susceptibility gene (ApoE) on chromosome 19(19q13)
Susceptibility gene locus on chromosome 12(12q)

Migraine
Susceptibility gene loci on chromosome 19(19p13); X(Xq24)

Non-insulin-dependent diabetes mellitus


Susceptibility gene loci on chromosome 12(12q); 2(2q)

Psoriasis
Susceptibility gene locus on chromosome 3(3q21)

GENETICS OF SCHIZOFRENIA
Since December 1996 genome scans were
conducted among hundreds of families & they
found that there exists linkage from of all
chromosomes 3, 4, 6, 8, 9, 11, 13, 14, 15, 17,
20, & 22
MODE OF INHERITANCE):

Non-Mendelian, reduced penetrance


Oligogenic of moderate effect
Polygenic of small effect

GENETIC DEFECTS THAT COULD CAUSE THE


INCIDENCE OF SCHIZOPHRENIA IS AT THE TIME
OF EMBRYONAL DEVELOPMENT, GROWTH AND
PLASTICITY, DURING NEURONAL MIGRATION TO
THE CORTEX, DURING ADOLESCENCE WHEN
NEURONAL PRUNING & DENDRITIC REBRANCHING
OCCUR, AND WHEN THE NORMAL PROCESS OF
AGEING & THE REDUCTION OF THE NUMBERS
AND SIZES OF CORTICAL NEURONS IS
HAPPENING.

THANK YOU
FOR YOUR
ATTENTION

FARMAKO-GENETIKA
ILMU YG MEMEPELAJARI PENGARUH GENETIK
THD RESPONS OBAT YANG BERBEDA PD PASIEN
DG ILMU INI KITA DPT MENYUSUN VARIASI
PROFIL ANTAR DNA ORANG DEMI MERAMALKAN
RESPONS OBAT
BISA DITENTUKAN KHASIAT & EFEK SAMPINGAN
LB DULU
KEPENTINGAN MEDIK & NILAI EKONOMIK
EFFICACY & SAFETY
PENGEMBANGAN OBAT YG SELARAS DG PENY.

MENINGKATKAN MUTU HIDUP


KESEHATAN
PENDIDIKAN
PEKERJAAN
EKONOMI / KEUANGAN
PERUMAHAN
MOBILITAS

MENINGKATKAN MUTU HIDUP


RASA SEJAHTERA SUBJEKTIF
KEPUASAN
KEBUDAYAAN
POLITIK / KEWARGANEGARAAN
HOBBY / PENGGUNAAN WAKTU
SENGGANG

03/02/15

Stress pasca trauma/

71

Clozapine in other conditions


Adjunct treatment for better sleep
pattern in drug abuse and dependent
patients esp. opiates, amphetamine,
methamphetamine
induce a better employment for chronic
disabled patient
improve longstanding thought loosening
of association in chronic patients

continued

ameliorate disgusting behavior


(coprophagy) & improve patients QoL
prevent upsurgence of postschizophrenic depression
prevent relapse and reduce re-admission
re-establish physical / emotional growth
no extrapyramidal symptoms
better prognosis

TERAPI BOLEH DICAMPUR


Dg neuroleptika tipik spt chlorpromazine,
haloperidol, perphenazine, trifluoperazine,
fluphenazine utk kasus akut gelisah & refrakter
dg methylphenidate(Ritalin) utk perilaku yg eratik
pd gg. spektrum autistik dg/tanpa gg hiperaktif
dg donepezil(Aricept) utk demensia insipien yg
bicara kotor & perilaku agresif
dg antidepresiva spt TCAs, SSRIs, Mianserine
Mirtazapine(Remeron)

HARAPAN DAN TANTANGAN MASA DEPAN


PENANGANAN SKIZOFRENIA
NEW OPPORTUNITIES AND CHALLENGES IN THE
TREATMENT OF SCHIZOPHRENIA

TINJAUAN PERSPEKTIF DISAJIKAN


PADA PERTEMUAN NASIONAL KE-2
TENTANG SKIZOFRENIA
DR. W.M. ROAN, DPM(Lond.)
PSIKIATER