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Menahem I. Krakowski, MD, PhD; Pal Czobor, PhD; Leslie Citrome, MD, MPh; Nigel Bark, MD; Thomas B. Cooper, MA

Arch Gen Psychiatry. 2006;63:622-629.

Context  Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.

Objective  To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.

Design and Setting  Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).

Main Outcome Measures  Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).

Results  Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.

Conclusions  Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.

Author Affiliations: Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Drs Krakowski, Czobor, and Citrome and Mr Cooper); New York University School of Medicine, New York (Drs Krakowski and Citrome); Albert Einstein College of Medicine, Bronx, NY (Dr Bark); Dov Pharmaceuticals, Hackensack, NJ (Dr Czobor); and Columbia University College of Physicians and Surgeons, New York (Mr Cooper).

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