Suicidal risk during treatment with clozapine: a meta-analysis

Suicide remains a major cause of premature mortality among patients with schizophrenia. Evidence of reduced suicidal risk with available psychiatric treatments is limited, but emerging data suggest such an effect of clozapine in chronically psychotic patients, leading us to compile the reported evidence.

We searched for published studies with contrasting rates of suicides or attempts by psychotic patients treated with clozapine vs. other agents.

Among six such studies, random-effects meta-analysis indicated a substantially lower overall risk of suicidal behaviors with clozapine vs. other treatments (risk-ratio 3.3; 95% confidence interval [CI] 1.7-6.3; p<0.0001). For completed suicides, the risk ratio (RR) was 2.9 ([CI 1.5-5.7]; p=0.002).

Long-term treatment with clozapine was associated with three-fold overall reduction of risk of suicidal behaviors. However, available findings are quantitatively inconsistent, well-designed studies remain rare, and the only randomized trial did not find reduced risk of completed suicide. Additional randomized comparisons among modern treatments for psychotic disorders are required to clarify their impact on mortality.