Reduction of suicidality during clozapine treatment of neuroleptic- resistant schizophrenia: impact on risk-benefit assessment

TLDR

Suicide occurs in 9–13 % of schizophrenic patients, with neuroleptic‑resistant or intolerant individuals at higher risk, and clozapine—though effective—has been limited by its potential for fatal agranulocytosis. The study aimed to compare suicidality in neuroleptic‑resistant versus responsive patients and to assess whether clozapine treatment reduces suicidality in the resistant group. A cohort of 237 responsive and 184 resistant schizophrenia or schizoaffective patients was examined, with 88 resistant patients receiving clozapine and followed prospectively for 6 months to 7 years, while prior suicidal episodes were similar across groups. Clozapine treatment led to a marked reduction in suicidality, eliminating high‑probability suicide attempts and improving depression and hopelessness, thereby supporting a reassessment of clozapine’s risk‑benefit profile and encouraging its broader use.

Abstract

Suicide has been reported to occur in 9%-13% of schizophrenic patients. It has been suggested that neuroleptic-resistant or neuroleptic-intolerant schizophrenic patients are at higher risk for suicide than neuroleptic-responsive patients. Clozapine is the treatment of choice for neuroleptic-resistant patients, but its use has been greatly limited because of its ability to cause potentially fatal agranulocytosis. The purpose of this study was to compare the suicidality of neuroleptic-resistant and neuroleptic-responsive patients and to determine if clozapine treatment decreased suicidality in the former group.Prior episodes of suicidality were assessed in a total of 237 neuroleptic-responsive and 184 neuroleptic-resistant patients with schizophrenia or schizoaffective disorder. Eighty-eight of the neuroleptic-resistant patients were treated with clozapine and prospectively evaluated for suicidality for periods of 6 months to 7 years.There was no significant difference in prior suicidal episodes between neuroleptic-responsive and neuroleptic-resistant patients. Clozapine treatment of the neuroleptic-resistant patients during the follow-up period resulted in markedly less suicidality. The number of suicide attempts with a high-probability of success decreased from five to zero. This decrease in suicidality was associated with improvement in depression and hopelessness.These results suggest a basis for reevaluation of the risk-benefit assessment of clozapine, i.e., that the overall morbidity and mortality of patients with neuroleptic-resistant schizophrenia are less with clozapine treatment than with typical neuroleptic drugs because of less suicidality. This conclusion also has implications for increasing the use of clozapine with neuroleptic-responsive patients.