Clozapine and Olanzapine Treatment of Aggression

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Clozapine
* Drug: Olanzapine
* Drug: Haloperidol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clozapine<br>During the first 6 weeks clozapine was gradually increased to 500 mg/day and then continued. For the next period, it could vary from 200-800 mg/day; | Drug: Clozapine<br>* 500 mg/day<br>* Other names: clozaryl;|
| Experimental: Olanzapine<br>During the first 6 weeks olanzapine was increased to 20 mg and remained fixed for until the end of six week. During the last 6 weeks olanzapine could vary from 10 to 30 mg/day | Drug: Olanzapine<br>* 20 mg/day<br>* Other names: zyprexa;|
| Active Comparator: Haloperidol<br>During the first 6 weeks haloperidol was increased to 20 mg and remained fixed for until the end of six week. During the last 6 weeks the dose could vary from 10 to 30 mg/day | Drug: Haloperidol<br>* 20 mg/day<br>* Other names: Haldol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of aggressive incidents | The Modified Overt Aggression scale (MOAS) was used to record all aggressive incidents. The primary measure was the total score on the MOAS as well as the score on the MOAS physical aggression subscale | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychiatric Symptoms | Psychiatric symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) weekly for the first 4 weeks and then bi-weekly for the remainder of the study | 12 weeks | 
| Side effects of medications | The side effects of the medications were measured with the ESRS on a weekly basis for the duration of the study | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, aggression, clozapine, olanzapine