The Protective Effect of Clozapine on Suicide

Brian J. Lee, MD, PhD, shares his insights on original research published in The Journal of Clinical Psychiatry, “The Protective Effect of Clozapine on Suicide: A Population Mortality Study of Statewide Autopsy Records in Maryland.” Clozapine is the oldest and most effective of the second-generation antipsychotics. It is the only antipsychotic with FDA indication for treatment-resistant schizophrenia and reduction of suicidal behavior in schizophrenia patients. As Dr Lee explains, previous studies, such as the InterSePT study, showed that clozapine reduces suicide-related outcomes like suicidal ideation or attempts, but most studies do not have enough power to show whether it impacts the actual number of suicide deaths. This impact is an important distinction, as most people who die by suicide do not have a history of suicide ideation or attempts. By studying blood serum levels of clozapine and olanzapine collected from statewide autopsy records, Dr Lee and colleagues found that individuals who had been prescribed clozapine were half as likely to die by suicide as those prescribed olanzapine. What constitutes the chemical or biological cause of this protective effect is largely unknown. Possibilities include clozapine’s superior efficacy in reducing psychotic symptoms; its binding to dopamine, serotonin, histamine, and anticholinergic receptors; its effect on gene expression changes; and its effect on antioxidant processes, inflammation, and stress pathways. Ultimately, while clozapine is the most efficacious antipsychotic medication, its mechanism of action is still poorly understood.
Visit Psychiatrist.com to read the full study: bit.ly/478Ch73
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Presented by The Journal of Clinical Psychiatry
Brian J. Lee, MD, PhD, is a psychiatry resident in the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

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