Effects on Suicidal Risk: Comparison of Clozapine to Other Second-Generation Antipsychotics

Ross J. Baldessarini, MD

Massachusetts General Hospital, McLean Hospital
Effects on Suicidal Risk: Comparison of Clozapine to Other Second-Generation Antipsychotics

Scientific Abstract

Background: Clozapine is the only treatment with regulatory-recognition of lowering suicidal risk, at least in schizophrenia patients. It remains uncertain whether such effects extend to other second- generation antipsychotic drugs (SGAs) or other diagnoses.

Methods: We searched for reports on rates of suicidal behavior during treatment with clozapine and other SGAs compared to other treatment options, and analyzed the contrasts by random- effects meta-analysis to obtain pooled Odds Ratios (ORs) with 95% confidence intervals (CIs). Results: We identified 35 paired comparisons of SGAs vs. other treatments. Overall, there was moderate superiority of all SGAs over alternatives (OR=0.52, p=0.004; Table 1). This effect was large and consistent with clozapine in 7/7 trials (OR=0.23, p<0.0001), but not with other SGAs in 28 other trials (OR=0.94, p=0.450; Fig. 1, Table 2). Efficacy of specific other SGAs ranked: risperidone ≥ olanzapine ≥ aripiprazole; suicidal risk was somewhat greater with ziprasidone and quetiapine than their comparators, but comparisons among non-clozapine SGAs were not significant.

Conclusions: The ability of clozapine to reduce risk of suicides and attempts in schizophrenia patients appears to be a unique effect not shared with other modern antipsychotic drugs, and remains untested in other disorders.

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Authors

Ross J. Baldessarini, MD