Photo Credit: Wildpixel

The following is a summary of “Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case-control study in Finland,” published in the April 2024 issue of Psychiatry by Rubio et al.

Clozapine, the only approved drug for treating schizophrenia, has been known to develop a severe side effect, agranulocytosis. 

Researchers conducted a retrospective study analyzing the risk of clozapine in inducing agranulocytosis. 

They studied all individuals in Finland diagnosed with schizophrenia or schizoaffective disorder from 1972 to 2014. The Kaplan-Meier model of time was used to track agranulocytosis diagnosis over 22 years (1996-2017). Later, a nested case-control model was developed by matching age, sex, and time since diagnosis and being in an incident cohort on a 1 to 5 ratio, comparing clozapine vs. non-clozapine treatment. 

The results found 61,769 people with schizophrenia or schizoaffective disorder (14,037 on clozapine, 47,732 on non–clozapine). The mean age of patients was 46.67 years (IQR 34.44-57.61), where 30,721 (49.7%) were female and 31,048 (50.3%) were male. Among those patients, 398 were diagnosed with agranulocytosis (231 were treated with clozapine, and 167 were treated with non-clozapine). Agranulocytosis incidence was 1.37% for clozapine (95% CI 0.58-3.16) vs. 0.13% for non-clozapine (0.04-0.23). The risk of clozapine-induced agranulocytosis decreased with more prolonged use (aOR 36.01 [16.79-77.22]  at less than 6 months to 4.38 [1.86-10.34] after 54 months). One clozapine-related agranulocytosis death occurred out of 3,559 individuals starting clozapine.

Investigators concluded that the risk of agranulocytosis with clozapine decreases over time but remains slightly higher than that with other antipsychotics. This risk is small compared to clozapine’s significant benefits, like improved life expectancy. Relaxing monitoring could boost clozapine’s benefits.

Source: thelancet.com/journals/lanpsy/article/PIIS2215-0366(24)00097-X/abstract#%20