Clozapine-treated patients with schizophrenia at risk for ileus, pneumonia

Ileus and pneumonia occur more frequently than previously reported among individuals with schizophrenia treated with clozapine, reveals a recent study, noting that such conditions also contribute to increased mortality. 

In total, 2,659 participants in the FinnGen biobank project were diagnosed with schizophrenia and had clozapine prescriptions, with longitudinal electronic health record follow-up for up to 25 years following clozapine initiation. 

The authors then identified diseases and health-related events occurring during clozapine use, with adjustments for disease severity. They also examined the incidence and recurrence of adverse drug events over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics.  

Over a median follow-up of 12.7 years after clozapine initiation, 27 out of 2,157 diseases and health-related events were enriched during clozapine use. These events were categorized as follows: seizures, tachycardia, gastrointestinal hypomotility, pneumonia, and other acute respiratory tract infections, along with a heterogeneous group, including neutropenia and type 2 diabetes, among others. 

Twenty years after clozapine initiation, the cumulative incidence estimates were 5.3 percent for ileus (severe gastrointestinal hypomotility) and 29.5 percent for pneumonia. Both events significantly correlated with a higher incidence of mortality among users of clozapine (ileus: odds ratio, 4.5; pneumonia: odds ratio, 2.8). 

Additionally, two CYP genes contributed to the risk of pneumonia. Specifically, decreased genotype-predicted CYP2C19 and CYP1A2 activities correlated with an increased pneumonia risk. 

"Pneumonia and ileus call for improved utilization of available preventive measures,” the authors said.