Suicide and schizophrenia: clozapine and the InterSePT study. International Clozaril/Leponex Suicide Prevention Trial.

Suicide is one of the most serious of schizophrenic symptoms and claims the life of 9% to 13% of patients. The annual rate of suicide in schizophrenic patients is reported to be in the range of 0.4% to 0.8%, a rate that has remained constant despite the introduction of antipsychotic therapy and attendant case-management systems. The risk of suicide is not significantly different in neuroleptic-resistant or -responsive schizophrenic patients. A study of 421 schizophrenic patients reported no significant difference in the incidence of lifetime and current episodes of suicidality in treatment-resistant and -responsive patients. A number of studies with clozapine, an atypical antipsychotic, have demonstrated an 80% to 85% reduction in suicide in neuroleptic-resistant patients. This is accompanied by a decrease in depression and psychopathology and improved cognition. Clozapine's modulation of serotonergic, noradrenergic, cholinergic, and dopamine function may be the biological basis for the reduction in suicide. Weekly contact with patients, for white blood cell monitoring, has also been put forward as one explanation. To further confirm suicide risk reduction as a benefit of clozapine therapy, the International Clozaril/Leponex Suicide Prevention Trial (InterSePT) is currently being conducted. This large, prospective treatment study will compare the rate of suicide attempts and completions in schizophrenic patients at high risk of suicide randomly assigned to receive clozapine or olanzapine. The bias of weekly visits will be excluded. Results should be available in 2001.