Chronic violence and hostility in schizophrenic patients represent a serious problem which impacts on the perpetrators, other patients and caregivers. In preliminary studies, we have identified a group of schizophrenic patients who evidence persistent violence and hostility linked to specific schizophrenic symptoms. These patients are responsible for a high percentage of all inpatient assaults. The literature suggests that clozapine (CLO) has specific anti- aggressive effects and it improves psychotic symptoms and cognitive impairments similar to those which we identified in these patients. Olanzapine's (OLZ) without the latter's potentially serious side effects suggests that it may have an important place in the treatment of these patients. We will examine the examine the comparative efficacy of CLO, OLZ and standard agent haloperidol (HAL) in the treatment of persistent. We will also how underlying symptoms and deficits are associated with persistent violence and how they improve with each of these three treatments. Violent patients (N=212) will enter a 12-week clinical trial in which they will be randomized to either CLO, OLZ or HAL under double-bind conditions. Outcomes measures include the Modified Overt Aggression Scale, the Buss-HAL under double-blind conditions. Outcomes measured include the Modified Overt Aggression Scale, the Buss-Durkee Hostility inventory, and the NOSIE. Patients' reduction in psychotic symptoms will be assessed by PANSS and CGI. Reduction in cognitive impairment will be assessed by the Wisconsin Card Sorting Test, in impulsivity by the Barrat Impulsiveness scale. It is hypothesized that: 1) the effects of CLO on physical assaults, hostility and social functioning will be superior to those of OLZ, which, in turn, will be superior to HAL's. 2) Improvement in the outcome variables-violence, hostility and social functioning-will be related to improvement in underlying symptoms, i.e. ability to utilize environmental feedback, impulsivity, and psychosis. Similar to the outcome measures, these symptoms will improve more with CLO than OLZ and more with OLZ than HAL.
