This was a double-blind randomized study with three treatment arms: clozapine, olanzapine and haloperidol. We compared these three medications in the treatment of aggressive behavior over a 12 week period.

Objective: The purpose of our study was the investigation of the effect of atypical antipsychotic agents on interpersonal violence and aggression.

We compared the efficacy of two atypical antipsychotic agents, clozapine and olanzapine with one another and with haloperidol in the treatment of physical assaults and other assaultive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.

Method: The subjects were 110 physically assaultive inpatients diagnosed with schizophrenia or schizoaffective disorder.

They were randomly assigned to treatment with clozapine (N=37), olanzapine (N=37) or haloperidol (N=36) in a 12-week, double-blind trial. Incidents of overt aggression were recorded and their severity was scored with the Modified Overt Aggression Scale (MOAS). Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). We also assessed various side effects and monitored vital signs and drew bloods.

Inclusion Criteria:

• Age: 18 to 60 years.
• Diagnosis of schizophrenia or schizoaffective disorder.
• Aggression: One episode of physical assault directed at another person in the hospital and persistence of violence/hostility for two weeks, as evidenced by the presence of some other physical, verbal or property assault or hostility, which would result in a score of 4 or more on the Positive and Negative Syndrome Scale (PANSS) Hostility Item.

Exclusion Criteria:

• Patients who were hospitalized for more than a year
• Patients who had a history of nonresponse to clozapine, olanzapine or haloperidol (defined as a lack of improvement despite a contiguous adequate trial of medication)
• Patients who had a history of clozapine, olanzapine, or haloperidol intolerance
• Patients who had medical conditions that would be adversely affected by any of these three medications.
• Patients who received a depot antipsychotic within 30 days before randomization.