European Psychiatry 20 (2005) 403408

http://france.elsevier.com/direct/EURPSY/

Original article

Effectiveness of clozapine, olanzapine, quetiapine, risperidone,

and haloperidol monotherapy in reducing hostile and aggressive behavior
in outpatients treated for schizophrenia:
a prospective naturalistic study (IC-SOHO)
Istvan Bitter a,*, Pal Czobor b,c,d, Martin Dossenbach e, Jan Volavka b,c
a

Department of Psychiatry and Psychotherapy, Semmelweis University, Balassa u. 6, 1083 Budapest, Hungary
b
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
c
New York University, New York, NY, USA
d
DOV Pharmaceutical, Inc., Hackensack, NJ, USA
e
Eli Lilly Ges.m.b.H., Vienna, Austria
Received 29 September 2004; accepted 25 January 2005
Available online 03 August 2005

Abstract
Objective. Antipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression.
Method. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic
treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this noninterventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N = 7655). The
presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and
prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment
groups (combined N = 3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had
complete data.
Results. Hostile/aggressive behavior was reduced during the treatment period. Olanzapine and risperidone were significantly superior to
haloperidol and to clozapine in this respect. These results remained essentially unchanged when adjusting for baseline imbalances in age,
gender, age of onset, and substance abuse.
Conclusions. As monotherapy, both olanzapine and risperidone were superior to haloperidol and clozapine in reducing aggression. The
relative lack of effectiveness of clozapine may be specific to this study population.
2005 Elsevier SAS. All rights reserved.
Keywords: Schizophrenia; Aggression; Antipsychotics

1. Introduction
Persons diagnosed with schizophrenia and other major
mental disorders are at a higher risk for committing aggressive acts than those without such diagnosis. This elevation of
risk has been confirmed in many epidemiological studies performed in the United States, Europe, and elsewhere [20].
Aggressive behavior is dangerous, it is a frequent reason for
* Corresponding author. Tel./fax: +36 1 303 6244.
E-mail address: bitter@psych.sote.hu (I. Bitter).
0924-9338/$ - see front matter 2005 Elsevier SAS. All rights reserved.
doi:10.1016/j.eurpsy.2005.01.009

admission to a psychiatric unit, interferes with discharge planning and reintegration of patients into the community, and
contributes to the stigmatization of the mentally ill. Even
though most of the aggressive behavior taking place in the
community is perpetrated by persons who have no major mental disorders, and the majority of the persons who do have
such disorders are not aggressive, aggressive behavior among
the mentally ill is a serious public health problem.
The long-term goal of treatment of aggressive patients is
to decrease the frequency and intensity of episodes of violent
behavior. This may be related to efficacious control of psy-

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I. Bitter et al. / European Psychiatry 20 (2005) 403408

chosis, decrease in impulsivity, relief of dysphoria, and

improvement in cognition. Choice of a first-line agent is
dependent upon the specific underlying disorder and expectation of a treatment response.
Atypical antipsychotics, especially clozapine, appear to
reduce hostility over time [4,8,1417,23], independent of their
effects in reducing hallucinations and delusions, or increasing sedation [2,22]. This was confirmed in a double blind
14-week randomized clinical trial comparing the specific
aggression-reducing effects of clozapine with those of olanzapine, risperidone, and haloperidol in 157 inpatients with
schizophrenia or schizoaffective disorder with a history of
sub-optimal treatment response to conventional antipsychotics [5]. Clozapine reduced hostility significantly more than
either haloperidol or risperidone. Failure of risperidone to
demonstrate superiority to haloperidol in these treatmentrefractory patients contrasts an earlier positive study with
treatment-responsive patients [6]. It may be that the effects
of risperidone on hostility differ for patients considered to be
treatment-resistant to typical antipsychotics.
Quetiapine may also preferentially reduce hostility and
aggression in treatment-responsive acute schizophrenia [3].
In another report, olanzapine-treated patients experienced a
significantly greater improvement in behavioral agitation than
did the haloperidol-treated patients [11]. An observational
study compared the effectiveness of long-term treatment with
olanzapine and risperidone in reducing aggressive behavior
among patients with schizophrenia in the community [18].
The subjects were followed for 3 years. Patients who remained
on olanzapine for 12 months or longer exhibited a statistically significant decrease of aggressive behavior in comparison with baseline, but the reduction in patients who remained
on risperidone did not reach the level of statistical significance. Direct statistical comparison between the two treatments in terms of decrease in aggressive behavior over time
was not reported. The authors concluded that olanzapine treatment conferred an advantage over risperidone in reducing
aggression. Treatment adherence mediated the association
between olanzapine-treatment and reduced aggressive behavior.
At this time, the weight of the evidence favors clozapine
as specific treatment for aggressive patients with schizophrenia, with demonstrated superiority to haloperidol and perhaps risperidone. Furthermore, atypical antipsychotics appear
superior to typical ones (such as haloperidol) in their effects
on aggression.
Studies of effects of various treatments on aggression were
usually conducted in seriously ill psychiatric inpatients. It is
not clear how these results will generalize to outpatients who
are less ill, but are exposed to the opportunities to use drugs
and alcohol as well as to general stresses of coping with independent life outside of institutions. We now present a large
observational study of aggressive behavior in outpatients diagnosed with schizophrenia.

2. Subjects and methods

The Intercontinental Schizophrenia Outpatient Health Outcomes project (IC-SOHO) is an ongoing, 3 years observational study of antipsychotic treatments of schizophrenia. The
study is being conducted in 27 countries in Africa, the Middle
East, Asia, Central and Eastern Europe, and Latin America.
Effectiveness and safety data are presently available for the
baseline and the 3 and 6 month time points. The sample baseline characteristics [13] and antipsychotic effectiveness results
at 3 and 6 months time points in the IC-SOHO studies have
been reported [7]. Sexual functioning of the patients participating in the IC-SOHO study has been described [1]. Separate reports on the SOHO results in the Central and Eastern
European regions have been published [12,19].
The clinical status is assessed primarily by the Clinical
Global ImpressionsSeverity of Illness rating scale (CGI-S)
[9]. The CGI-S was adapted [10] to include additional four
symptom domains (positive, negative, depressive, and cognitive symptoms). The subjects met the following entry criteria: 1) Clinical diagnosis of schizophrenia (ICD-10 or DSMIV). 2) Initiated or changed antipsychotic medication for the
treatment of schizophrenia. 4) Presented with the normal
course of care in an outpatient setting or in hospital when
admission was planned for the initiation or change of antipsychotic medication with discharge planned within 2 weeks.
5) At least 18 years old. 6) Not simultaneously participating
in an interventional study, the patients (or their legal representatives) were required to provide at least oral consent; written consent requirements were determined by local regulations in each participating country. Participating psychiatrists
enrolled patients, at their discretion, into one of two treatment arms: patients who initiated or changed their antipsychotic medication to olanzapine, and those who initiated or
changed to another antipsychotic. Enrollment proceeded by
alternating patients until a total of 10 (five patients in each
group) were entered. Psychiatrists were told to make their
treatment decisions based on standard clinical practice, independent of the study, and then evaluate whether patients were
eligible for inclusion based on the entry criteria and the alternating structure of enrollment.
A total of 7655 patients were enrolled (see Fig. 1). There
were 5018 patients who were initiated or changed to monotherapy with olanzapine, clozapine, risperidone quetiapine,
or haloperidol at baseline. A subset of these patients
(N = 3135) had data available at the baseline and at both 3and 6-month follow-up time points and maintained their
monotherapy. The patients in this subset were the subjects of
the current study.
The inclusion criterion of sustained monotherapy was
adopted primarily because long treatment periods are required
to evaluate effectiveness. In general, aggressive behavior
occurs at low frequency and thus long treatment periods are
needed to evaluate aggression-reducing effects. This and other
selection criteria displayed in Fig. 1 resulted in a reduced
subject sample in comparison with the numbers published by
Dossenbach et al. (2004).

I. Bitter et al. / European Psychiatry 20 (2005) 403408

405

This patient has suffered from diagnosed substance

dependency/abuse in the past. Analogous statements about
alcohol were presented. No formal diagnostic criteria were
employed. We created a single binary variable (called substance abuse). This variable was defined by presence or
absence of any degree of abuse or dependence on any substance or alcohol at any time in the patients history prior to
enrollment.
This information was obtained as a part of the patient interview; the investigators may have also obtained collateral information from other sources. To date, data are available for three
time points: baseline, 3- and 6-months follow-ups.
2.1. Statistical analyses

Fig. 1. Patient Accounting Diagram for ICR-SOHO.

In this report, we focus primarily on the data pertaining to

violence. At baseline, the participating investigators answered
the following question: Has the patient exhibited verbal or
physical hostility/aggression in the past 6 months? At the
follow-up time points, the same question was asked but the
time period covered was not the past 6 months; instead, it
read since the last data collection. This binary variable
(called hostility in subsequent text) was the principal dependent variable in our primary analyses. No additional questions regarding the severity or frequency of aggressive behavior were asked.
Thus, the hostility variable was a rudimentary, inadequately defined descriptor of hostile and aggressive behavior. To evaluate its validity, we determined whether this variable, assessed at baseline, was associated with its typical
correlates that are well described in the large existing literature [20], and that were available in this sample. The correlates were: male gender, younger age, earlier onset of illness,
and history of substance abuse (defined below).
Participating investigators were asked to endorse one of
the following statements: a) This patient never suffered from
diagnosed substance dependency/abuse in the past, or b)

The P = 0.05 level (two-sided) was adopted for all analyses for statistical significance. The principal statistical analysis tested the null-hypothesis of no difference among the five
treatment groups. Difference among the treatment groups in
the likelihood of hostility over time was investigated by the
generalized estimating equations method (GEE). This method
is an extension of traditional linear repeated measures models to handle non-normally distributed observations such as
binary and ordered categorical data, and counts of events
occurring during a given period of time. The binary variable
hostility (present/absent) defined for each of the two 6-months
study periods (pretreatment, post-treatment) was applied as
the dependent variable. Treatment group was used as the
between subject variable. Time served as the within subject
(repeated measures) factor. The time (overall change over
time) and the interaction effect between group and time (group
difference in change over time) constituted the main interest
in the analyses. If the interaction effect reached statistical significance, post-hoc pairwise analyses were conducted to
examine the individual group differences. In addition to the
GEE analyses, logistic regression analyses were conducted
to compare the five treatments with respect to the incidence
of hostility among those subjects who did not display hostility at baseline.
The effect size for change in hostility status over time was
estimated using the odds ratios (OR) computed from the GEE
for each pairwise drug comparison that reached statistical significance in the analyses described above.
Multiple logistic regression analysis was performed to
investigate whether male gender, younger age, earlier onset
of disease (age at first contact) and history of substance abuse
were associated with a greater likelihood of hostility
assessed at baseline. The time unit selected for analyzing the
age-related variables was 5 years. Published data suggest that
this interval is meaningful for assessing the effects of age on
aggressive behavior in mental illness ([20], pp. 160161).
3. Results
The demographic and clinical description of the subject
sample is displayed in Table 1. The treatment groups showed

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I. Bitter et al. / European Psychiatry 20 (2005) 403408

Table 1
Demographic and clinical characteristics of patients studied a
Treatment

Clozapine
Olanzapine
Quetiapine
Risperidone
Haloperidol

Number of patients
in treatment group

Age
Nb

Mean

S.D.

Age at first contactc

N
Mean S.D.

143
2118
104
650
120

131
2035
96
622
117

34.3
34.90
36.1
36.4
35.3

11.6
12.0
12.5
12.5
10.2

134
1942
98
597
112

23.9
26.6
27.9
26.8
26.1

7.9
9.3
8.4
9.5
9.1

Genderc
N
%
Males
141 67.4
2107 54.1
103 44.7
648 53.7
120 53.3

Number
of males
95
1140
46
348
64

Substance use history

N
% (with
Number
history)
with history
140
6.4
9
2085
3.0
63
104
4.8
5
643
3.6
23
120
5.8
7

Complete data not available for some patients enumerated in this table.
N = the total number of patients with complete data for any given variable depicted in the table.
c
Significant treatment group differences were detected for this variable (see text).

statistically significant differences in the age at first contact

with a helping agency (F = 3.6, df = 4; P < 0.007) and in the
gender distribution (chi-square = 13.7; d = 4; P < 0.008).
Post-hoc pairwise comparisons indicated that clozapine
patients were significantly (P < 0.05) younger at the age of
first contact than the patients on olanzapine, quetiapine, and
risperidone; no other significant group differences were
detected for this variable. The clozapine group also contained significantly (P < 0.05) higher proportion of males than
any other treatment group; no other difference reached statistical significance. The baseline levels of hostility are displayed in Table 2; the differences between treatment groups
at baseline were not statistically significant (chi-square = 6.05,
df = 4, P = 0.195).
The principal analysis was the Generalized Estimating
Equation for change of hostility over time. Since the question regarding hostility asked at enrollment pertained to the
period of preceding 6 months, we combined the information
collected at the two follow-up visits (at 3- and 6-months) into
one variable: if the patient was reported to exhibit hostile/
aggressive behavior at one or both of the two follow-up visits, hostility was rated as present. We then used the analysis
to compare hostility ratings in two 6-month periods (before
and during treatment).
The analysis showed a significant effect of treatments (chisquare = 18.39; df = 4; P < 0.001), time (chi-square = 98.98;
df = 1; P < 0.000), and a significant treatment x time interaction (chi-square = 11.81; df = 4; P < 0.019). This interaction
indicated that the treatments differed in their effects over time.
Post-hoc individual comparisons between each atypical drug
and haloperidol indicated significant superiority of olanzap-

ine (chi-square = 7.64; P < 0.006) and risperidone (chisquare = 7.74; df = 1; P < 0.005) over the typical antipsychotic in decreasing the likelihood of hostility from baseline
to endpoint. These results are displayed in Table 2. Post-hoc
pairwise comparisons of all atypicals with each other revealed
significant superiority of risperidone (chi-square = 4.55;
df = 1; P < 0.033) and olanzapine (chi-square = 4.05; df = 1;
P < 0.044) over clozapine.
The effect size (OR with 95% confidence limits [CL]) of
improvement in hostility status over time was 1.92 (1.21
3.01) for olanzapine over haloperidol; 2.09 (1.243.52) for
risperidone over haloperidol; 1.83 (1.053.20) for risperidone over clozapine; 1.67 (1.012.75) for olanzapine over
clozapine.
Younger age, male gender, early age of onset, and comorbid substance use disorders are well known to elevate the risk
for aggressive behavior [1]. The analyses described above,
were therefore, repeated using these four variables as covariates. The inclusion of these covariates has not resulted in substantial changes.
However, as expected, each of these four variables was
significantly associated with hostility assessed at baseline.
Younger age: OR(95%CL) = 1.049 (1.0181.080), chisquare = 10.06, P = 0.002; male gender: OR(95%CL) = 1.170
(1.0401.316), chi-square = 6.80, P = 0.009; earlier age of
onset: OR(95%CL) = 1.072 (1.0321.113), chi-square =
13.00, P = 0.0003; substance use: OR(95%CL) = 2.015
(1.4842.736), chi-square = 20.18, P < 0.0001.
To assess the effects of treatments on the incidence of hostile and aggressive behavior, we studied the subset of subjects (N = 2069) who showed no evidence of such behavior

Table 2
Proportions of patients demonstrating hostile/aggressive behavior at baseline and at 6 months
Medication

Clozapine
Olanzapine
Quetiapine
Risperidone
Haloperidol

N (total
treated)
143
2118
104
650
120

Baseline (6 months)
Number of patients
Proportiona
with hostile behavior
48
0.336
724
0.342
35
0.337
207
0.319
52
0.433

Treatment (6 months)
Standard error Number of patients
Proportiona
with hostile behavior
0.040
24
0.168
0.010
231
0.111b
0.046
16
0.154
0.018
60
0.092b
0.045
31
0.258

Standard error
0.031
0.007
0.035
0.011
0.040

a
Proportions of patients showing hostility/aggression during 6 months prior to enrollment (baseline) and during 6 months of treatment with one of four
atypical drugs or haloperidol.
b
P < 0.05 vs. haloperidol and clozapine.

I. Bitter et al. / European Psychiatry 20 (2005) 403408

during the 6-month baseline period. Logistic regression used

hostility during the 6-month treatment as the dependent variable. The overall treatment effect was statistically significant
(chi-square = 10.40, df = 4; P < 0.034). Olanzapine treatment was associated with significantly fewer cases of emerging hostility in comparison with haloperidol (chisquare = 8.87; df = 1; P = 0.003). No other statistically
significant pairwise treatment differences with haloperidol
were detected. These results were similar after adjusting for
age, male gender and comorbid substance use disorders.
The relationship between drug type, polypharmacy, and
hostility was examined in a series of descriptive statistics and
chi-square analyses. The likelihood of remaining on monotherapy at 3 and 6 months was unrelated to the baseline hostility status. Drug type was related to the likelihood of maintaining monotherapy for both time periods (3 months: Chisquare = 24.4, df = 4, P < 0.0001; 6 months: Chi-square =
55.4, df = 4, P < 0.0001). The proportion of subjects with
maintained montoherapy for 3 months was 70.7% (181/256)
for haloperidol, 78.8% (186/236) for clozapine, 79.9%
(2575/3221) for olanzapine, 72.5% (137/189) for quetiapine
and 75% (837/1116) for risperidone. For the 6-months period
the analogous proportions were the following: 47.3%
(121/256) for haloperidol, 61.9% (146/236) for clozapine,
66.2% (2132/3221) for olanzapine, 55.0% (104/189) for quetiapine and 58.7% (655/1116) for risperidone.

4. Discussion
Medications had different effects on the prevalence of hostility during the 6-month treatment period. The superiority of
risperidone and olanzapine to haloperidol was expected, but
the superiority over clozapine was not. We hypothesized that
the relatively poor outcome with clozapine was related to the
fact that clozapine patients had an earlier onset of symptoms,
were more likely to be male, were younger, and had more
comorbid substance use disorders. However, the outcome
results remained essentially unchanged when we accounted
for all these potentially confounding factors. The baseline levels of hostility in patients given clozapine, risperidone, or olanzapine were similar. Nevertheless, it is possible that the psychiatrists were more likely to prescribe clozapine for patients
who were perceived as treatment resistant. Such selection bias
might explain the relatively poor performance of clozapine.
Furthermore, the apparent lack of the expected effect of clozapine on aggression, may have been caused by the relatively
low number of patients given this treatment, and a consequent lack of power to detect an effect.
The study has several additional limitations. It was open,
and the expectations of the patients and the investigators may
have affected the results. The project was not primarily
designed to study aggression, and the data on this behavior
are, therefore, rudimentary. There is no information on the
severity or frequency of aggressive behavior, and the data on
verbal and physical aggression are commingled. Neverthe-

407

less, the aggressive behavior assessed by our simple method

was significantly associated with its expected correlates:
younger age, male gender, earlier onset of illness, and history
of substance use disorder. These associations suggest that the
assessment of aggressive behavior had some validity.
A further limitation is that patients who received a combination of two or more antipsychotic drugs or were switched
to another antipsychotic drug during the 6 months of the study
period were not included in the study. Furthermore, it is not
clear whether the results observed in this study will generalize to Western societies; violent behavior in schizophrenia
patients in the developing countries shows certain differences in comparison with the developed countries [21].

5. Conclusions
This report presents analyses of aggression-reducing
effects of clozapine, olanzapine, quetiapine, risperidone, and
haloperidol during the first 6 months of a large multicenter
prospective observational study of schizophrenia outpatients. Antipsychotics differed in their effectiveness against
hostile and aggressive behavior. Olanzapine and risperidone
were superior to haloperidol and, surprisingly, to clozapine
in reducing hostility and aggression. This apparent superiority to clozapine may have been an artifact due to non-random
assignment or other limitations of the study design. The study
was not originally designed to study aggression, and the information on aggressive behavior, is therefore, limited. However, the reported aggressive behavior was associated with its
usual correlates in this sample; these associations support the
validity of the aggression reports.
This study is based on a large number of patients and,
despite limitations, it provides an important comparison of
effectiveness of several antipsychotics under the real world
conditions.

Acknowledgements
The IC-SOHO study was supported by a research grant
from Eli Lilly and Company, Indianapolis, Ind., USA. The
idea for this ancillary study of aggression emerged in discussions between Drs Bitter and Volavka. Data analyses for this
report were designed and implemented by Drs Czobor and
Volavka at the Nathan S. Kline Institute for Psychiatric
Research, Orangeburg, NY, USA, Eli Lilly and Company provided the Nathan S. Kline Institute scientists access to the
IC-SOHO database, but no funding for the write up. In the
initial stages of the present ancillary study of aggressive
behavior Dr. Bitter was employee of Eli Lilly and Company.

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References
[1]

Bitter I, Basson BR, Dossenbach MR. Antipsychotic treatment and

sexual functioning in first-time neuroleptic-treated schizophrenic
patients. Int Clin Psychopharmacol 2005;20(1):1921.
[2] Buckley P, Bartell J, Donenwirth K, Lee S, Torigoe F, Schulz SC.
Violence and schizophrenia: clozapine as a specific antiaggressive
agent. Bull Am Acad Psychiatry Law 1995;23:60711.
[3] Chengappa KN, Goldstein JM, Greenwood M, John V, Levine J. A
post hoc analysis of the impact on hostility and agitation of quetiapine
and haloperidol among patients with schizophrenia. Clin Ther 2003;
25(2):53041.
[4] Chiles JA, Davidson P, McBride D. Effects of clozapine on use of
seclusion and restraint at a state hospital. Hosp Community Psychiatry 1994;45:26971.
[5] Citrome L, Volavka J, Czobor P, Sheitman B, Lindenmayer J-P,
McEvoy J, et al. Effects of clozapine, olanzapine, risperidone, and
haloperidol on hostility in treatment-resistant patients with schizophrenia and schizoaffective disorder. Psychiatr Serv 2001;52:15104.
[6] Czobor P, Volavka J, Meibach RC. Effect of risperidone on hostility in
schizophrenia. J Clin Psychopharmacol 1995;15:2439.
[7] Dossenbach M, Erol A, el Mahfoud KM, Shaheen MO, Sunbol MM,
Boland J, et al. Effectiveness of antipsychotic treatments for
schizophrenia: interim 6-month analysis from a prospective observational study (IC-SOHO) comparing olanzapine, quetiapine, risperidone, and haloperidol. J Clin Psychiatry 2004;65(3):31221.
[8] Ebrahim GM, Gibler B, Gacono CB, Hayes G. Patient response to
clozapine in a forensic psychiatric hospital. Hosp Community Psychiatry 1994;45:2713.
[9] Guy W. ECDEU Assessment Manual for Psychopharmacology.
Rockville: National Institute of Mental Health; 1976.
[10] Haro JM, Kamath SA, Ochoa S, Novick D, Rele K, Fargas A, et al.
The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.
Acta Psychiatr Scand 2003;416(Suppl):1623.
[11] Kinon BJ, Roychowdhury SM, Milton DR, Hill AL. Effective resolution with olanzapine of acute presentation of behavioral agitation and
positive psychotic symptoms in schizophrenia. J Clin Psychiatry
2001;62(Suppl 2):1721.

[12] Korb FA, Trzebiatowska I, Janikova E, Winkler-Skaza V, Ilies D,

Peciukaitiene D, et al. The Intercontinental Schizophrenia Outpatient
Health Outcomes (IC-SOHO) study: Baseline clinical and functional
characteristics and antipsychotic use of patterns in the Central and
Eastern Europe (CEE) region. Psychiatria Danubina 2003;15:16374.
[13] Korb FA, Yenilmez C, Belaid A, Ghazi M, Omar A-E, Bitter I. The
intercontinental schizophrenia outpatient health outcomes (ic-soho)
study: baseline clinical and functional characteristics and antipsychotic use patterns in the North Africa and Middle Eastern (amea)
region. South African Psychiatry Review 2004;7:2734.
[14] Maier GJ. The impact of clozapine on 25 forensic patients. Bull Am
Acad Psychiatry Law 1992;20:297307.
[15] Mallya AR, Roos PD, Roebuck-Colgan K. Restraint, seclusion, and
clozapine. J Clin Psychiatry 1992;53:3957.
[16] Ratey JJ, Leveroni C, Kilmer D, Gutheil C, Swartz B. The effects of
clozapine on severely aggressive psychiatric inpatients in a state
hospital. J Clin Psychiatry 1993;54:21923.
[17] Spivak B, Roitman S, Vered Y, Mester R, Graff E, Talmon Y, et al.
Diminished suicidal and aggressive behavior, high plasma norepinephrine levels, and serum triglyceride levels in chronic neurolepticresistant schizophrenic patients maintained on clozapine. Clin Neuropharmacol 1998;21(4):24550.
[18] Swanson JW, Swartz MS, Elbogen EB, Van Dorn RA. Reducing
violence risk in persons with schizophrenia: olanzapine versus risperidone. J Clin Psychiatry 2004;65(12):166673.
[19] Treuer T, Dossenbach M, Meder J, Herman E, Pecenak J, Tavar R,
et al. Observational study of schizophrenia outpatients in Central and
Eastern Europe: 3- and 6-month efficacy and safety results. Socialna
Psihijatria 2004;32:4957.
[20] Volavka J. Neurobiology of Violence. 2 ed. Washington, DC: American Psychiatric Publishing, Inc.; 2002.
[21] Volavka J, Laska E, Baker S, Meisner M, Czobor P, Krivelevich I.
History of violent behaviour and schizophrenia in different cultures.
Analyses based on the WHO study on determinants of outcome of
severe mental disorders. Br J Psychiatry 1997;171:914.
[22] Volavka J, Zito JM, Vitrai J, Czobor P. Clozapine effects on hostility
and aggression in schizophrenia. J Clin Psychopharmacol 1993;13:
2879.
[23] Wilson WH, Claussen AM. 18-month outcome of clozapine treatment
for 100 patients in a state psychiatric hospital. Psychiatr Serv
1995;46:3869.