REDUCTION OF SUICIDALITY DURING CLOZAPINE TREATMENT OF NEUROLEPTIC-RESISTANT SCHIZOPHRENIA - IMPACT ON RISK-BENEFIT ASSESSMENT

Objective: Suicide has been reported to occur in 9%-13% of schizophren ic patients. It has been suggested that neuroleptic-resistant or neuro leptic-intolerant schizophrenic patients,are at higher risk for suicid e than neuroleptic-responsive patients. Clozapine is the treatment of choice for neuroleptic-resistant patients, but its use has been greatl y limited because of its ability to cause potentially fatal agranulocy tosis. The purpose of this study was to compare the suicidality of neu roleptic-resistant and neuroleptic-responsive patients and to determin e if clozapine treatment decreased suicidality in the former group. Me thod: Prior episodes of suicidality were assessed in a total of 237 ne uroleptic-responsive and 184 neuroleptic-resistant patients with schiz ophrenia or schizoaffective disorder. Eighty-eight of the neuroleptic- resistant patients were treated with clozapine and prospectively evalu ated for suicidality for periods of 6 months to 7 years. Results: Ther e was no significant difference in prior suicidal episodes between neu roleptic-responsive and neuroleptic-resistant patients. Clozapine trea tment of the neuroleptic-resistant patients during the follow-up perio d resulted in markedly less suicidality. The number of suicide attempt s with a high-probability of success decreased from five to zero. This decrease in suicidality was associated with improvement in depression and hopelessness. Conclusions: These results suggest a basis for reev aluation of the risk-benefit assessment of clozapine, i.e., that the o verall morbidity and mortality of patients with neuroleptic-resistant schizophrenia are less with clozapine treatment than with typical neur oleptic drugs because of less suicidality. This conclusion also has im plications for increasing the use of clozapine with neuroleptic-respon sive patients.