The rate of suicide among schizophrenics has been reported to be eight- to nine-times that of normal controls. Yet, no evidence has appeared that suggests that treatment with typical antipsychotics reduces the suicide rate in persons with schizophrenia. Nor is there strong evidence demonstrating reduction of suicide rate in association with treatment with antidepressants or mood stabilizers.

In contrast, some evidence suggests that the atypical antipsychotic clozapine may dramatically reduce rates of suicide attempt and completion. Dr. Meltzer and colleagues have reported marked reduction in the rate of suicide attempts in a sample of treatment-resistant schizophrenic patients during two years of treatment with clozapine: The rate of suicide attempts fell by 85 percent over two years of clozapine treatment, compared with that during the two years prior to treatment with clozapine. Moreover, some of the suicide attempts during clozapine treatment occurred during the first few months of treatment, possibly reflecting insufficient duration of clozapine treatment.

Consistently, the expected rate of suicide fell by 75 percent in a 1997 analysis of the U.S. registry of patients receiving clozapine. At that time, the registry included 50,000 patients treated for up to four years. Of 38 suicides reported, nearly 20 percent occurred during the first month of treatment. Overall mortality was 83 percent lower in clozapine-treated patients than in patients who discontinued treatment.

In May of 2001, however, Rosenheck and colleagues published a study in the American Journal of Psychiatry, reporting no difference in suicide completion rates between 1,415 patients treated with clozapine and twice as many matched controls not treated with clozapine.

That study was seriously flawed, according to Dr. Meltzer, who pointed to its use of controls poorly matched for suicide risk, depression, and treatment-resistance; its high proportion of patients treated with clozapine for less than six months; and its failure to specify continuity of clozapine treatment during the period when suicide rates were compared. Even with its serious flaws, that study showed a trend toward lower suicide rate in the two-thirds of patients treated with clozapine for at least one year (0.49% versus 1.1%, p = 0.07), perhaps suggesting that even brief treatment with clozapine may be associated with reduced suicidal behavior.

Other atypical antipsychotics may affect suicide rates similarly. Pharmaceutical company research suggests that olanzapine, quetiapine, risperidone and ziprasidone may have antidepressant effects and may reduce suicide rates, compared to typical neuroleptics. For example, a study of 2,700 patients showed 75- to 80-percent reductions in suicidal behavior during treatment with quetiapine and risperidone (compared with rates of suicidal behavior during haloperidol treatment) with no significant difference between the two atypicals.

Although more research is needed, Dr. Meltzer believes that atypical antipsychotics may reduce the risk of suicide in patients with schizophrenia.