Tuesday, March 29, 2022

Long-Term Clozapine Use May Slightly Increase Risk of Some Blood Cancers

People who take the antipsychotic clozapine for more than five years may be at a slightly increased risk of developing blood cancers such as leukemia or lymphoma compared with people who take other antipsychotics, a report in The Lancet Psychiatry has found.

“To ensure a wider access to clozapine therapy, which is the most effective antipsychotic drug, our results suggest that patients and caregivers should be informed about early signs of hematological malignancies, just as they are currently encouraged to monitor early signs of agranulocytosis,” wrote Jari Tiihonen, M.D., of the Karolinska Institutet and colleagues. (Agranulocytosis is a rare but serious condition that occurs when there is an extremely low number of white blood cells called granulocytes.)

The findings were based on data from a national register collected from 61,889 people treated for schizophrenia in inpatient settings in Finland between 1972 and 2014. From this group, Tiihonen and colleagues identified 375 patients aged 18 to 85 years with a first-time diagnosis of lymphoid and hematopoietic tissue malignancy between 2000 and 2017 following their schizophrenia diagnosis; these patients were matched with 3,734 patients with schizophrenia who did not have a cancer diagnosis.

The researchers found that patients who used clozapine for less than one year or for one to four years did not have any increased risk of a hematological malignancy; however, patients who used clozapine for five years or more were about three times as likely as patients who had never used clozapine to be diagnosed with a hematological malignancy. The researchers also found that the risk of malignancy increased in a dose-response manner: a patient who took clozapine daily for a total number of doses between 1,000 and 2,999 had 1.79 increased odds of a hematological malignancy, whereas a patient who took clozapine daily for a total number of doses of 5,000 or more had 3.35 increased odds of a hematological malignancy (there was no increased risk of hematological malignancy among people who took clozapine daily for a total number of doses of 999 or fewer). Exposure to other antipsychotics was not associated with increased odds of these malignancies.

During the 17-year follow-up, 37 deaths were due to hematological malignancy among patients exposed to clozapine versus three deaths from agranulocytosis, the authors noted.

“Long-term clozapine use has a higher effect on mortality due to lymphoma and leukemia than due to agranulocytosis,” Tiihonen and colleagues wrote. “However, acknowledging that the absolute risk is small compared with the previously observed absolute risk reduction in all-cause mortality is important. … [M]ental health clinicians should be vigilant for signs and symptoms of hematological malignancy in patients treated with clozapine.”

In a commentary accompanying the article, Dan Siskind, M.B.B.S., M.P.H., of the University of Queensland and colleagues wrote, “[T]he findings by Tiihonen and colleagues are a signal of an uncommon but important adverse outcome. … They merit further investigation but should not be interpreted as a reason to deny a marginalized group access to potentially transformative and lifesaving treatment, to which there are few alternatives.”

For related information, see the American Journal of Psychiatry article “Clozapine, Long-Acting Injectables (and Polypharmacy?) Superior in U.S. and International Registries.”

(Image: iStock/Oleg Elkov)

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