Predictors of Relapse in the Year
After Hospital Discharge Among
Patients With Schizophrenia
Rebecca Schennach, M.D.
Michael Obermeier
Sebastian Meyer
Markus Jger, M.D.
Max Schmauss, M.D.
Gerd Laux, M.D.
Herbert Pfeiffer, M.D.
Objective: Relapse and its predic-
tors were examined among pa-
tients with schizophrenia in the
year after hospital discharge.
Methods: The sample included
200 patients with schizophrenia
participating in a German multi-
center study. Relapse was defined
as a worsening of psychopatho-
logical symptoms or rehospitaliza-
tion in the year after hospital dis-
charge. Predictors examined were
variables related to course of ill-
ness and to response and remis-
sion at discharge. Results: Fifty-
Dr. Schennach, Mr. Obermeier, Mr. Mey-
er, Prof. Jger, Dr. Seemller, Prof. Mller,
and Prof. Riedel are affiliated with the
Department of Psychiatry and Psy-
chotherapy, Ludwig-Maximilians-Univer-
sity, Nussbaumstreet 7, 80336 Munich,
Germany (e-mail: rebecca.schennach@
med.unimuenchen.de). Prof. Riedel is also
with the Psychiatric Clinic, Vinzenz-von-
Paul-Hospital, Rottweil, Germany. Prof.
Schmauss is with the Psychiatric Clinic,
District Hospital Augsburg, Augsburg,
Germany. Prof. Laux is with the Psychi-
atric Clinic, Inn-Salzach Hospital,
Wasserburg-Inn, Germany. Dr. Pfeiffer
is with the Psychiatric Clinic, Isar-Am-
per Hospital, Munich-Haar, Germany.
Prof. Naber is with the Department of
Psychiatry and Psychotherapy, Universi-
ty of Hamburg, Hamburg, Germany.
Prof. Schmidt is with the Department of
Psychiatry and Psychotherapy, Universi-
ty of Mainz, Mainz, Germany. Prof.
PSYCHIATRIC SERVICES o ps.psychiatryonline.org o January 2012 Vol. 63 No. 1
Dieter Naber, M.D.
Lutz G. Schmidt, M.D.
Wolfgang Gaebel. M.D.
Joachim Klosterktter, M.D.
Isabella Heuser, M.D.
Wolfgang Maier, M.D.
Matthias R. Lemke, M.D.
two percent of participants had a
relapse. Patients whose symptoms
were not in remission at discharge
were more likely to have a relapse,
as were those who had more se-
vere symptoms and more side ef-
fects at discharge. Those who ex-
perienced a relapse were less like-
ly to be taking a second-genera-
tion antipsychotic at discharge,
less likely to have a positive atti-
tude toward treatment adherence,
and less likely to be employed.
Conclusions: The high rate of re-
lapse among patients with schizo-
Gaebel is with the Department of Psychi-
atry and Psychotherapy, Heinrich-
Heine-University, Duesseldorf, Ger-
many. Prof. Klosterktter is with the De-
partment of Psychiatry and Psychothera-
py, University of Cologne, Cologne, Ger-
many. Prof. Heuser is with the Depart-
ment 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 Psychi-
atry and Psychotherapy, University of
Gttingen, Gttingen, Germany. Prof.
Klingberg is with the Department of Psy-
chiatry and Psychotherapy, University of
Tbingen, Tbingen, Germany. Prof.
Gastpar is with the Fliedner Clinic,
Berlin, Germany.
Eckart Rther, M.D.
Stefan Klingberg, M.D.
Markus Gastpar, M.D.
Florian Seemller, M.D.
Hans-Jrgen Mller, M.D.
Michael Riedel, M.D.
phrenia highlights the need to im-
prove current treatment strate-
gies. (Psychiatric Services 63:87
90, 2012)
F or many patients with schizophre-
nia, the course of illness is charac-
terized by frequent relapses with exac-
erbations 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 func-
tioning and poor adherence to treat-
ment (2). Research applying recently
proposed consensus definitions of out-
come to examine the association be-
tween the status of patients with schiz-
ophrenia at hospital dischargesuch
as whether they have responded to
treatment and whether their symp-
toms are in remissionand subse-
quent relapse is scarce.
In addition, clinical implications
from earlier studies are limited be-
cause many focused only on first-
episode patients or used data from
randomized controlled trials known
to exclude severely ill or suicidal pa-
tients. Another difficulty for re-
searchers in this field is the lack of a
consensus definition and generally
accepted criteria for relapse. For ex-
ample, a recent review that compared
the relapse prevention potential of
various antipsychotics noted that 11
87
different criteria were used in 17
studies (3). In this study we used a
broad definition of relapse to examine
relapse in a heterogeneous group of
patients in order to reduce potential
limitations on our findings.
Methods
Data were collected as part of a multi-
center naturalistic follow-up study,
the German Research Network on
Schizophrenia. The study was con-
ducted at 11 university-affiliated psy-
chiatric hospitals and three nonuni-
versity-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 in-
clusion. Exclusion criteria were a head
injury, a history of major general med-
ical illness, and alcohol or drug de-
pendence. All study participants pro-
vided written informed consent. The
study protocol was approved by the lo-
cal ethics committees. After discharge
patients were followed up for assess-
ment 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 char-
acteristics 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 (HAMD-
17); higher scores on both instruments
indicate greater illness severity. Ex-
trapyramidal symptoms were exam-
ined with the Simpson-Angus Scale.
The Global Assessment of Function-
ing 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 Neu-
roleptic Treatment Scale assessed
well-being. To evaluate the patients
premorbid adjustment the subscale
for premorbid social-personal adjust-
ment from the Phillips Scale was em-
88
ployed. The instruments were admin-
istered within the first three days after
admission, biweekly during the pa-
tients 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 cor-
relation>.8).
Patients were categorized as expe-
riencing or not experiencing a re-
lapse. Relapse was defined by using
two items from the standard forms.
The first item evaluates an acute ex-
acerbation of the illness, and the sec-
ond item explicitly examines rehospi-
talization because of a worsened psy-
chopathological 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 ad-
mission 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, unusu-
al thought content, hallucinatory be-
havior, conceptual disorganization,
mannerisms and posturing, blunted
affect, social withdrawal, and lack of
spontaneity. The time criterion for re-
mission was not considered at dis-
charge if the patient had been hospi-
talized for six months or less.
First, univariate tests were used to
compare patients with and without a
relapse during the year after dis-
charge. 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-operat-
ing characteristic curve. The area un-
der the curve (AUC) is a measure of
the overall discriminative power. An
AUC value of .5 indicates no discrim-
inative ability, and an AUC value of
1.0 indicates perfect discriminative
power. All statistical analyses were
performed with the statistical pro-
gram R2.11.1.
Overall, 474 patients were enrolled
in the naturalistic multicenter study.
Forty-six patients dropped out for var-
ious reasons, 28 were discharged from
the hospital within seven days of ad-
PSYCHIATRIC SERVICES o ps.psychiatryonline.org o January 2012 Vol. 63 No. 1
mission, and 167 dropped out during
the acute treatment phase and follow-
up. Patients who dropped out were
significantly older than patients who
did not (p=.006) and scored signifi-
cantly lower at discharge on the
PANSS total score (p<.001). The two
groups did not differ in sociodemo-
graphic and clinical characteristics.
Because of missing PANSS data at the
one-year follow-up assessment, 33 pa-
tients were excluded. Thus data were
analyzed for a sample of 200 patients.
Results
The sample included 107 men and 93
women. The meanSD age was
36.310.1 years, and the mean dura-
tion of illness was 8.39.4 years. The
mean number of lifetime hospitaliza-
tions 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 an-
tipsychotics, 130 (65%) were receiv-
ing 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 one-
year assessment, no significant change
in patients psychopathology, function-
ing, occurrence of extrapyramidal
symptoms, and subjective well-being
was observed. At discharge, 114 pa-
tients (57%) were classified as treat-
ment responders, and symptoms were
in remission for 114 patients (57%). At
follow-up, 108 (54%) were classified as
responders, and symptoms were in re-
mission 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 assess-
ment, those who had experienced a re-
lapse 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 experi-
enced a relapse, 78 (75%) were hospi-
talized 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
the follow-up period were significantly
less likely to be employed at hospital
discharge (p=.002). In addition, those
with a relapse were significantly less
likely at discharge to be treated with a
second-generation antipsychotic (p=
.04) and had a significantly worse atti-
tude toward treatment (p=.007). Also,
patients who had a relapse were signif-
icantly more likely to report side ef-
fects (p<.001) at discharge, even
though no significant between-group
differences were observed at dis-
charge in the defined daily dose of the
second-generation or first-generation
antipsychotics. Furthermore, patients
who relapsed scored significantly high-
er at discharge on the PANSS total
score (p=.02), the PANSS negative
subscore (p=.02), and the HAMD-17
total score (p=.01), indicating more
negative and depressive symptoms.
Patients whose symptoms were not in
remission at discharge were signifi-
cantly more likely to relapse within the
year after discharge than those whose
symptoms were in remission at dis-
charge (p=.05) (Figure 1).
Four significant relapse predictors,
as measured at hospital discharge, were
identified: a higher HAMD-17 score
(p<.001), more side effects (p<.001), a
worse attitude to treatment (p=.002),
and not having a job (p=.01). The pre-
diction model reached significance
(p<.001), with satisfactory predictive
power (AUC=.76). The CART model
confirmed that reporting more side ef-
fects at discharge (p<.001) and having a
worse attitude toward treatment adher-
ence at discharge (p=.007) were signif-
icant predictors of relapse. Significant
predictors by CART analysis at dis-
charge also included a higher PANSS
negative subscore (p=.04) and an inde-
pendent living situation (p<.001).
Discussion
The aim of this study was to identify
sociodemographic and clinical factors
that predicted relapse among patients
with schizophrenia so that these vari-
ables could be monitored during
treatment and specific strategies
could be adopted to prevent relapse.
In our sample, 52% of patients had a
relapse in the first year after hospital
dischargean alarmingly high pro-
portion. One possible explanation is
that the sample included chronically
PSYCHIATRIC SERVICES o ps.psychiatryonline.org o January 2012 Vol. 63 No. 1
Figure 1
Relapse during the year after hospital discharge among 200 patients, by whether
their symptoms had responded to treatment or were in remission at discharge
100
Response
80
Percentage
46
60
40
41
No response
20
0 0
Discharge
ill patients with a history of distinct
cycles of relapse. In addition, this
study was observational, and patients
received only monthly telephone calls
during follow-up. Unlike randomized
controlled studies, no extensive visits
or interventions were provided. How-
ever, the relapse rate in our study is
comparable to the rate of 42% found
in a study of relapse among patients
taking oral antipsychotics (4). In a
study that compared maintenance
treatment of first-episode patients
with risperidone and haloperidol for
one year and that defined relapse as a
marked clinical deterioration, Gaebel
and colleagues (5) found that no re-
lapses occurred. This finding may be
at least partly explained by the inclu-
sion of only first-episode patients in
the sample. In line with the findings
of that study, our results indicated
that patients experiencing a first
episode had a lower risk of relapse
during follow-up; however, the differ-
ence did not reach statistical signifi-
cance, which may be explained by the
small sample of first-episode patients
and therefore the limited statistical
power in our study.
As others have found, depressive
symptoms at hospital discharge in our
study were significant predictors of
relapse during the one-year follow-
up. In a three-year prospective, ob-
servational study in which 2,228 pa-
tients with schizophrenia were exam-
ined at 12-month intervals, Conley
(6) found that depressed patients
were significantly more likely than
those without depression to use re-
100
No relapse
No relapse
Remission
54% 80 54%
Percentage
46
60
%
40
%
40
No remission
Relapse
Relapse
20
59% 60%
1 year Discharge 1 year
lapse-related mental health services.
Also, Olfson and colleagues (7) as-
sessed clinical predictors of early re-
hospitalization among 262 patients
with schizophrenia three months af-
ter discharge and found early read-
mission to be significantly associated
with major depressive symptoms.
Consistently, negative symptoms have
also been associated with a worse
course of schizophrenia and a higher
rate of relapse, which our results con-
firm. Leifker and colleagues (8) have
shown that blunted affect and pas-
sive-apathetic social withdrawal ac-
counted for all of the variance in pre-
dicting social outcome among 194
outpatients with schizophrenia.
The fact that we found that patients
whose symptoms were in remission at
discharge were significantly less likely
to experience a relapse than those
whose symptoms were not in remis-
sion is not surprising, because one
would strongly expect that a patient
with greater improvement during the
acute treatment phase would have a
more favorable course of illness (9).
Several studies have demonstrated
that early and adequate symptom
control is the precondition of achiev-
ing a favorable long-term course of
the illness. Lambert and colleagues
(10), for example, followed over three
years 392 patients with schizophrenia
who had never received treatment
and found that remission within the
first three months after baseline as
the strongest predictor of subsequent
remission. Also, Wobrock and col-
leagues (11) found that nonremission
89
of symptoms after two weeks of treat-
ment was a significant predictor of
not achieving remission after three
months of treatment.
In our study side effects at dis-
charge were a significant predictor of
relapse in both prediction models.
Chabungbam and colleagues (12) ex-
amined sociodemographic and clini-
cal factors associated with relapse
among patients with schizophrenia
and found that those who experi-
enced a relapse were significantly
more likely to complain of moderate
to severe side effects of medication. A
possible explanation offered by the
authors was that patients with more
severe side effects may be those re-
ceiving a higher dosage of antipsy-
chotics to combat relapse. In regard
to antipsychotic treatment, we found
that patients treated with first-gener-
ation antipsychotics at discharge were
more likely to have a relapse during
follow-up, which is supported by re-
search data (3).
Like other researchers who have
assessed relapse predictors, we found
that a worse attitude toward adher-
ence at discharge was a significant
predictor; this is believed to be one of
the most reliable predictors of relapse
in schizophrenia research. In a study
of 477 patients with schizophrenia,
Laan and colleagues (13) found that
160 patients relapsed within six
months of hospital discharge. The au-
thors found that the relapse risk was
substantially lower when a patient
was properly adherent to the antipsy-
chotic therapy that was prescribed
during inpatient treatment. We also
found that having a job at discharge
was protective against relapse during
follow-up. The association between
employment status and relapse has
been previously noted. In an analysis
of three years of data for 6,516 pa-
tients with schizophrenia, Haro and
colleagues (14) found that social func-
tioning, as measured primarily by
having paid employment, was one of
the most important predictors of the
course of illness. The authors con-
cluded that the association between
paid employment and a more favor-
able course was due not only to the
positive influence of work itself but
also to other factors such as social
support and patient competencies.
90
This finding is somewhat in line with
our finding that independent living
status at discharge was protective
against relapse.
A strength of this study is the inclu-
sion of treatment outcome at hospital
discharge in the prediction model,
which also applied standardized defi-
nitions of outcome. Also, the natura-
listic study design is closer to a real-
world setting than a randomized con-
trolled trial. However, the naturalistic
design lacked sufficient control for
the effect of pharmacological treat-
ments. Rehospitalization was includ-
ed in the definition of relapse, but re-
hospitalization may not reflect exac-
erbation of the illness, which should
be considered in interpreting these
results. In addition, the study was
conducted in a single European
country, and the generalizability of
the results may thus be limited. An-
other limitation is that substance
abuse, a well-known factor in relapse,
could not be examined because pa-
tients with comorbid substance use
disorders were not included in the
study.
Conclusions
In this study, 52% of patients with
schizophrenia experienced a relapse
within the first year of hospital dis-
charge. Patients without a job, with a
higher HAMD-17 score, more medica-
tion side effects, and a poorer attitude
about treatment at the time of dis-
charge were more likely to have a re-
lapse 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 employ-
ment after discharge should also be
considered in treatment approaches.
Acknowledgments and disclosures
The study was performed within the frame-
work 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.
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