The use of clozapine in the treatment of aggressive schizophrenia

Can J Psychiatry. 1998 Jun;43(5):466-72. doi: 10.1177/070674379804300503.


The atypical antipsychotic drug clozapine was introduced to clinical practice in 1972. It is a dibenzodiazepine derivative with, among other known receptor site activities, a relatively high D1/D2 receptor affinity ratio. The serious side effects of bone marrow suppression and agranulocytosis delayed the acceptance of clozapine into common clinical practice but scrupulous application of a monitoring protocol led to adequate protection from these side effects. There is now a broad consensus about the benefits of clozapine which supports the use of clozapine as a first-line treatment of schizophrenia. There is good evidence that relapse and rehospitalization drop to 22% of the incidence in preclozapine treatment patients. The majority of responders are identified within 4 months of treatment. Clozapine has been demonstrated to be an effective treatment for neuroleptic refractory patients. Forty percent of clozapine-treated patients show significant improvement, with 11% of treated patients showing no residual psychosis. This review also describes the results of clozapine on aggressive and violent assault in a patient population characterized by severe functional deficits, typically chronic schizophrenia with severe impairment, chronic brain syndromes, and developmental handicap. Prior to the introduction of clozapine therapy, in a chronically disrupted milieu that precluded adequate psychosocial programming, seriously assaultive behaviour resulting in peer and staff injury was a common occurrence. Evidence suggests that clozapine is an effective medical treatment for the target symptoms of hostile agitation, threatening, and assaultive violence.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Administration, Oral
  • Aggression / drug effects*
  • Aggression / psychology
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacokinetics
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / adverse effects
  • Clozapine / pharmacokinetics
  • Clozapine / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Forensic Psychiatry
  • Humans
  • Lithium Carbonate / therapeutic use
  • Ontario
  • Restraint, Physical
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Social Isolation


  • Antipsychotic Agents
  • Lithium Carbonate
  • Clozapine