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Objective: Relapse and its predictors were examined among patients with schizophrenia in the
year after hospital discharge.
Methods: The sample included
200 patients with schizophrenia
participating in a German multicenter study. Relapse was defined
as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were
variables related to course of illness and to response and remission at discharge. Results: Fifty-
phrenia highlights the need to improve current treatment strategies. (Psychiatric Services 63:87
90, 2012)
Dr. Schennach, Mr. Obermeier, Mr. Meyer, Prof. Jger, Dr. Seemller, Prof. Mller,
and Prof. Riedel are affiliated with the
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Nussbaumstreet 7, 80336 Munich,
Germany (e-mail: rebecca.schennach@
med.unimuenchen.de). Prof. Riedel is also
with the Psychiatric Clinic, Vinzenz-vonPaul-Hospital, Rottweil, Germany. Prof.
Schmauss is with the Psychiatric Clinic,
District Hospital Augsburg, Augsburg,
Germany. Prof. Laux is with the Psychiatric Clinic, Inn-Salzach Hospital,
Wasserburg-Inn, Germany. Dr. Pfeiffer
is with the Psychiatric Clinic, Isar-Amper Hospital, Munich-Haar, Germany.
Prof. Naber is with the Department of
Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany.
Prof. Schmidt is with the Department of
Psychiatry and Psychotherapy, University of Mainz, Mainz, Germany. Prof.
Gaebel is with the Department of Psychiatry and Psychotherapy, HeinrichHeine-University, Duesseldorf, Germany. Prof. Klosterktter is with the Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. Prof. Heuser is with the Department of Psychiatry and Psychotherapy,
Charite Berlin, Campus Benjamin
Franklin, Berlin, Germany. Prof. Maier
is with the Department of Psychiatry and
Psychotherapy, University of Bonn,
Bonn, Germany. Prof. Lemke is with the
Department of Psychiatry, Alsterdorf
Hospital, Hamburg, Germany. Prof.
Rther is with the Department of Psychiatry and Psychotherapy, University of
Gttingen, Gttingen, Germany. Prof.
Klingberg is with the Department of Psychiatry and Psychotherapy, University of
Tbingen, Tbingen, Germany. Prof.
Gastpar is with the Fliedner Clinic,
Berlin, Germany.
PSYCHIATRIC SERVICES
or many patients with schizophrenia, the course of illness is characterized by frequent relapses with exacerbations of psychosis, often resulting
in the need for rehospitalization (1).
Patients with a history of relapse have
been shown to have a more complex
illness profile, associated with more
severe psychopathological symptoms,
substance use, impairments in functioning and poor adherence to treatment (2). Research applying recently
proposed consensus definitions of outcome to examine the association between the status of patients with schizophrenia at hospital dischargesuch
as whether they have responded to
treatment and whether their symptoms are in remissionand subsequent relapse is scarce.
In addition, clinical implications
from earlier studies are limited because many focused only on firstepisode patients or used data from
randomized controlled trials known
to exclude severely ill or suicidal patients. Another difficulty for researchers in this field is the lack of a
consensus definition and generally
accepted criteria for relapse. For example, a recent review that compared
the relapse prevention potential of
various antipsychotics noted that 11
87
Methods
Data were collected as part of a multicenter naturalistic follow-up study,
the German Research Network on
Schizophrenia. The study was conducted at 11 university-affiliated psychiatric hospitals and three nonuniversity-affiliated psychiatric hospitals.
All patients between the ages of 18
and 65 who were admitted to one of
the hospitals between January 2001
and December 2004 with a diagnosis
of schizophrenia, schizophreniform
disorder, delusional disorder, or
schizoaffective disorder according to
DSM-IV criteria were selected for inclusion. Exclusion criteria were a head
injury, a history of major general medical illness, and alcohol or drug dependence. All study participants provided written informed consent. The
study protocol was approved by the local ethics committees. After discharge
patients were followed up for assessment at specified time points. The
study reported here used data from
the one-year follow-up assessment.
DSM-IV diagnoses were verified by
clinical researchers. Information was
collected on sociodemographic characteristics and on variables related to
illness course and to attitude toward
treatment and treatment adherence
by using standard forms. Symptom
severity was assessed with the Positive
and Negative Syndrome Scale for
Schizophrenia (PANSS) and the
Hamilton Depression Scale (HAMD17); higher scores on both instruments
indicate greater illness severity. Extrapyramidal symptoms were examined with the Simpson-Angus Scale.
The Global Assessment of Functioning Scale (GAF) and the Social and
Occupational Functioning Assessment
Scale (SOFAS) were used to evaluate
functioning. The short version of the
Subjective Well-Being Under Neuroleptic Treatment Scale assessed
well-being. To evaluate the patients
premorbid adjustment the subscale
for premorbid social-personal adjustment from the Phillips Scale was em88
ployed. The instruments were administered within the first three days after
admission, biweekly during the patients hospital stay, at discharge, and at
follow-up. All raters had been trained
in use of the scales. A high interrater
reliability was achieved (intraclass correlation>.8).
Patients were categorized as experiencing or not experiencing a relapse. Relapse was defined by using
two items from the standard forms.
The first item evaluates an acute exacerbation of the illness, and the second item explicitly examines rehospitalization because of a worsened psychopathological condition. A positive
rating in for either item was defined
as a relapse.
The outcome of inpatient treatment
was defined as a 50% improvement in
PANSS total score from hospital admission to discharge. Remission was
determined by the consensus criteria
proposed by the PANSS developers
a score of 3 or less of the following
items for six months: delusions, unusual thought content, hallucinatory behavior, conceptual disorganization,
mannerisms and posturing, blunted
affect, social withdrawal, and lack of
spontaneity. The time criterion for remission was not considered at discharge if the patient had been hospitalized for six months or less.
First, univariate tests were used to
compare patients with and without a
relapse during the year after discharge. All variables with a p value of
<.10 in the univariate analysis were
tested as predictors of relapse by two
methods: logistic regression analysis
and classification and regression tree
(CART) analysis. The discriminative
ability of the regression model was
evaluated by using a receiver-operating characteristic curve. The area under the curve (AUC) is a measure of
the overall discriminative power. An
AUC value of .5 indicates no discriminative ability, and an AUC value of
1.0 indicates perfect discriminative
power. All statistical analyses were
performed with the statistical program R2.11.1.
Overall, 474 patients were enrolled
in the naturalistic multicenter study.
Forty-six patients dropped out for various reasons, 28 were discharged from
the hospital within seven days of adPSYCHIATRIC SERVICES
Results
The sample included 107 men and 93
women. The meanSD age was
36.310.1 years, and the mean duration of illness was 8.39.4 years. The
mean number of lifetime hospitalizations was 3.45.1. The mean age at
first treatment was 28.19.6 years. At
one-year follow-up 50 patients (25%)
were receiving first-generation antipsychotics, 130 (65%) were receiving second-generation antipsychotics,
18 (9%) were receiving first- as well as
second-generation antipsychotics, 22
(11%) were receiving tranquilizers,
and 27 (14%) were receiving mood
stabilizers. Forty-six patients (23%)
were also receiving antidepressants.
From hospital discharge to the oneyear assessment, no significant change
in patients psychopathology, functioning, occurrence of extrapyramidal
symptoms, and subjective well-being
was observed. At discharge, 114 patients (57%) were classified as treatment responders, and symptoms were
in remission for 114 patients (57%). At
follow-up, 108 (54%) were classified as
responders, and symptoms were in remission for 102 (51%) (Figure 1).
A total of 104 patients (52%) had at
least one relapse during the follow-up
period, and 34 (17%) had more than
one. At the one-year follow-up assessment, those who had experienced a relapse scored significantly higher on the
PANSS total score (p<.001) and all
PANSS subscale scores; they also had
significantly greater impairments as
measured by the GAF and SOFAS
(p<.001). Among patients who experienced a relapse, 78 (75%) were hospitalized as a result of the exacerbation of
their illness, and 26 (25%) were treated
for the relapse in an outpatient setting.
Patients who had a relapse during
20
60%
No relapse
Relapse
40
54%
40
%
60
Remission
Percentage
No relapse
80
No remission
59%
Relapse
20
54%
41
%
40
Response
60
No response
Percentage
80
100
PSYCHIATRIC SERVICES
100
46
Relapse during the year after hospital discharge among 200 patients, by whether
their symptoms had responded to treatment or were in remission at discharge
Discussion
Figure 1
46
0
Discharge
1 year
Discharge
1 year
Conclusions
In this study, 52% of patients with
schizophrenia experienced a relapse
within the first year of hospital discharge. Patients without a job, with a
higher HAMD-17 score, more medication side effects, and a poorer attitude
about treatment at the time of discharge were more likely to have a relapse during the year after discharge.
Therefore, providers should develop
strategies to enhance adherence and
diminish side effects before patients
are discharged from the hospital.
Helping patients maintain employment after discharge should also be
considered in treatment approaches.
Acknowledgments and disclosures
The study was performed within the framework of the German Research Network on
Schizophrenia, which is funded by the German
Federal Ministry for Education and Research
BMBF (grant 01 GI 0233).
The authors report no competing interests.
References
1.
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