Tuesday, April 30, 2024

Risks of Clozapine Decline Sharply After Six Months, May Warrant Reduced Monitoring

While clozapine increases an individual’s risk of agranulocytosis (a drop in a type of white blood cell that can be life threatening) more than other antipsychotics, the risk of a serious adverse event is minimal and drops steeply after the first year of use, according to a study published yesterday in Lancet Psychiatry. This study, which tracked nearly 62,000 people in Finland for up to 22 years, also found that the fatality rate among individuals who develop agranulocytosis is very low.

“More than half of the agranulocytosis events in patients treated with clozapine occurred during the initial 6 months,” wrote Jose M. Rubio, M.D., of the Feinstein Institutes for Medical Research in Manhasset, N.Y., and colleagues. “Notably, although purposeful, lifetime blood monitoring might be a deterrent to use clozapine for some patients and therefore lifting it from being mandatory after a cautionary period could facilitate the uptake of this underused drug.”

Rubio and colleagues studied 61,679 people who were diagnosed with schizophrenia or schizoaffective disorder in Finland, which has the highest rate of clozapine prescription worldwide. About one-quarter the individuals took clozapine, and three-quarters took other antipsychotics.

The researchers noted that antipsychotics as a class appear to be associated with an elevated risk of agranulocytosis during the initial six months of treatment. In fact, 231 individuals treated with clozapine developed the condition (1.37%) as well as 167 individuals treated with other antipsychotics (0.13%). However, the risk of agranulocytosis appeared to abate after six months among those taking other antipsychotics, while the risk of developing clozapine-induced agranulocytosis decreased steeply over time but remained elevated.

The researchers found an increased risk of agranulocytosis for those treated with higher than standard doses of clozapine, those taking it in combination with other psychotropic medication, and those with medical comorbidities. For every 3,559 individuals who initiated clozapine, only one person died due to agranulocytosis.

“Rubio and colleagues make a sensible, and cautious, call for a reduction in the frequency of blood monitoring for those on clozapine and to stop after 3 years of treatment,” according to an accompanying editorial by Jack B. Fanshawe and Belinda R. Lennox, D.M., of the University of Oxford. However, given the homogeneity of the Finnish population, “[f]urther studies in more diverse clinical cohorts are crucial to ensure any flexibility in haematological monitoring can be safely applied to these populations,” they wrote.

For related information, please see the Psychiatric News story, “FDA Reviewing Clozapine REMS to Determine if Monitoring Requirements Can Be Modified.”


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