Are the 8 Finnish Deaths Explained by Agranulocytosis More Important than the Thousands of Suicide Deaths Associated with the Lack of Use of Clozapine? Reflections on Clozaphobia

06/07/2026

AI Summary

Clozapine markedly reduces suicide in schizophrenia, potentially preventing up to 80% of deaths and saving hundreds of thousands worldwide.
Agranulocytosis mortality is tiny compared with benefits; per 10,000 extra prescriptions, 400 suicides prevented versus 3 agranulocytosis deaths.
Regulatory caution and clozaphobia have limited clozapine use; recent FDA changes eased monitoring, yet prescriber reluctance risks thousands of avoidable suicides.

J Clin Psychopharmacol. 2026 Jul 6. doi: 10.1097/JCP.0000000000002218. Online ahead of print.

ABSTRACT

PURPOSE/BACKGROUND: In 1975 clozapine was associated with 8 agranulocytosis deaths in Finland, leading to clozaphobia. In 1989 clozapine was approved in the United States (US) by the Food and Drug Administration (FDA) for treatment-resistant schizophrenia and in 2003 for suicide prevention. The FDA contributed to clozaphobia by focusing on the risk of agranulocytosis while ignoring other risks. On November 19, 2024, an FDA clozapine meeting reported 140,000 annual prescriptions and 0.03% mortality from agranulocytosis, and allowed patients’ advocates to argue that the restrictions were costing millions of lives. In June 2025 the package insert eliminated the centralized database and hematological monitoring became “recommended”.

METHODS: Four 2025 clozapine articles from this journal are used to initiate a rational discussion on suicide prevention and agranulocytosis risk. Suicide takes 5% of patients with schizophrenia, while long-term treatment with clozapine may prevent up to 80% of these deaths.

FINDINGS/RESULTS: US prescribers not willing to use clozapine need to consider long-acting injectable antipsychotics unless they want to contribute to the future 194,000 suicide deaths in patients with schizophrenia. For every future increase of 10,000 long-term clozapine prescriptions in schizophrenia, 400 US lives will be saved from suicide, costing 3 from agranulocytosis.

IMPLICATIONS/CONCLUSIONS: More widespread clozapine usage may save an unknown number of lives among other treatment-resistant US psychiatric patients and in other countries. Worldwide, 4 million people with schizophrenia will kill themselves in the coming years; every 10% increase in clozapine usage may lead to saving 320,000 lives at a cost of 2,400 deaths from agranulocytosis.

PMID:42403189 | DOI:10.1097/JCP.0000000000002218

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