A recent Finnish study found that pneumonia and severe gastrointestinal complications are more common with the most effective schizophrenia medication than previously thought. These side effects increase mortality, highlighting the need for better monitoring. Genetic testing could help identify high-risk patients.
About one-third of patients with schizophrenia do not respond to conventional medications, leaving them with one effective treatment option: clozapine. Clozapine's most serious side effect, a life-threatening drop in white blood cell levels, has been effectively controlled through strict monitoring. However, recent findings show that the drug has other serious side effects.
Pneumonia and Intestinal Blockage are Common Among Clozapine Users
Using data from the FinnGen study, the researchers found that clozapine-induced pneumonia and intestinal blockage, a severe form of gastrointestinal hypomotility, are much more common than previously reported. As many as 30% of schizophrenia patients on clozapine developed pneumonia, and 5% experienced intestinal blockage within 20 years of starting the medication. Both side effects were linked to an increased risk of death.
- The exceptionally long follow-up time in our study allowed us to assess clozapine's side effects more accurately. Previous studies have mainly identified side effects that occur shortly after starting the medication, explained Dr. Juulia Partanen, a research physician at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.
In addition to Finland's comprehensive long-term health data registries, the country is also a global leader in clozapine use, which facilitated the study.
Genetic Testing Could Help Identify High-Risk Patients
The study also suggests that genetic testing could help identify patients at high risk for clozapine-induced pneumonia. This association was observed in two genes involved in clozapine metabolism.
Variants in these genes that slow the breakdown of clozapine significantly increased the risk of pneumonia. For example, 15% of patients with the ultrarapid variant of the CYP2C19 gene developed pneumonia, compared to nearly 30% of those with the slow variant.
Call for Enhanced Monitoring and Prevention
Clozapine use has not been without complications. Fifty years ago, it was pulled from the market due fatal side effects, but was later reintroduced because of its superior efficacy.
The study confirms that the serious drop in white blood cell levels, which initially led to clozapine's withdrawal, has been successfully controlled through careful monitoring. However, other severe side effects, such as pneumonia and intestinal blockage, require more diligent monitoring and better preventive measures, including vaccinations.
- Clozapine-induced pneumonia and intestinal blockage should be taken as seriously as the white blood cell drop once was. With improved monitoring and reduced mortality, the use of this highly effective drug could become both safer and potentially also more widespread, says Dr. Jukka Koskela who led the study at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki.
The study was recently published in the American Journal of Psychiatry.
Original publication: Partanen J. et al. High Burden of Ileus and Pneumonia in Clozapine-Treated Individuals With Schizophrenia: A Finnish 25-Year Follow-Up Register Study, American Journal of Psychiatry, DOI: https://doi.org/10.1176/appi.ajp.20230744
