How antipsychotic drugs like clozapine affect blood cancer risk: Latest findings to know when treating schizophrenia

By Scott Cunningham, MD, PhD
Published June 23, 2022

Key Takeaways

  • Long-term treatment of schizophrenia with clozapine increases the risk of hematologic malignancies (lymphoma and leukemia).

Putting It Into Practice

Clozapine is an atypical anti-psychotic with superior clinical efficacy, but does not block dopamine D2 receptors, thus avoiding the extrapyramidal side effects. Approximately 30% of patients with schizophrenia are resistant to treatment with anti-psychotics; however, it has been estimated that < 20% of clozapine-eligible patients are prescribed clozapine.

Clozapine can be safely used in select patient with schizophrenia with careful monitoring and adherence to treatment guidelines.

Why this study matters

Despite the superior clinical efficacy of clozapine in patients with treatment-resistant schizophrenia, patients must be informed about the untoward effects, including agranulocytosis, weight gain, diabetes, myocarditis, seizures, and the newly-described hematologic malignancies.

Study design

A nationwide case-control study involving patients with schizophrenia (18-85 years of age) was conducted using data obtained from the Finnish national registers.

The study cohort consisted of 375 patients with schizophrenia diagnosed with a hematologic malignancy who were age-, gender-, and time since diagnosis of schizophrenia-matched with approximately 10 patients with schizophrenia without a hematologic malignancy (n=3734).

Results and conclusion

During a mean follow-up of 12.3 years, the incidence of hematologic malignancies among patients with schizophrenia who were prescribed clozapine was 0.7% (event rate = 61/100,000 person-years). The types of malignancies were as follows: lymphomas (n=305); leukemia (n=42); myelomas (n=22); and other (n=6).

During a mean follow-up of 12.9 years, the incidence of hematologic malignancies among patients with schizophrenia who were prescribed anti-psychotics other than clozapine was 0.5% (event rate = 41/100,000 person-years).

The adjusted odds ratio for a hematologic malignancy in clozapine-users compared to users of other anti-psychotics was 3.35.

Original Source

Tiihonen J, Tanskanen A, Bell JS, et al. Long-term treatment with clozapine and other antipsychotic drugs and the risk of haematological malignancies in people with schizophrenia: A nationwide case-control and cohort study in Finland. The Lancet Psychiatry. DOI:

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