The Effects of Clozapine on Aggression and Substance Abuse in Schizophrenic Patients

Aggressive behavior in schizophrenic patients, although infrequent, is a serious problem. It is, however, a relatively common reason for psychiatric admission and poses an increasing threat as more patients are cared for in the community. There is a strong association between substance abuse and violent behavior, and comorbid substance abuse in schizophrenia is also a major problem. The recent introduction of the atypical antipsychotics has brought hope for the pharmacologic management of this group of patients. These newer agents are thought to have antiaggressive effects and perhaps decrease cravings for illicit substances and alcohol. Data from a number of studies have demonstrated that clozapine has antiaggressive effects. A retrospective analysis of 331 schizophrenic patients assessed the effects of clozapine on hostility and aggression. At baseline, 31.4% of patients showed overt physical aggression, and after an average of 47 weeks of treatment with clozapine, this rate had fallen to 1.1%. The antiaggressive effects of clozapine were relatively specific and could not be explained by sedation or general antipsychotic effects. These effects were more pronounced than the effects on other symptoms and were also present in those patients who showed the highest pretreatment levels of hostility and aggression. Clozapine may also be of benefit in the treatment of schizophrenic patients with comorbid substance abuse. After 6 months of treatment with clozapine, substance abusers and nonabusers with schizophrenia or schizoaffective disorder showed similar improvements on measures of psychopathology and psychosocial functioning.