Clozapine and Solid Cancer Risk in Lithuania: A Population-Based Cohort Study

Background: People with schizophrenia may experience altered cancer risk because of lifestyle-, healthcare access-, and treatment-related factors. Evidence on the solid cancer risk associated with clozapine remains limited. We aimed to assess solid cancer incidence among clozapine users in Lithuania between 2013 and 2021. Methods: We conducted a retrospective population-based cohort study linking National Health Insurance Fund records with the Lithuanian Cancer Registry. Patients with schizophrenia treated with clozapine during 2013-2021 were followed from the first recorded clozapine prescription until death, emigration, or 31 December 2021. Standardized incidence ratios (SIR) for cancers were calculated as the ratio of observed cancer cases in the clozapine user cohort to the expected number of cancers in the general Lithuanian population. Results: The cohort included 3473 clozapine users and 91 incident cancers. Overall cancer incidence was lower than expected in males. Among men with at least 3 years of clozapine exposure, prostate cancer incidence was reduced (SIR 0.47, 95% CI 0.22-0.98). Among women with at least 3 years of exposure, corpus uteri cancer incidence was increased (SIR 2.42, 95% CI 1.21-4.83). Conclusions: Current evidence on solid cancer incidence among clozapine users remains limited. Prolonged exposure may be associated with cancer-specific rather than uniform changes in risk. These exploratory findings should be interpreted cautiously and support continued attention to cancer surveillance and further large-scale pharmacoepidemiological studies with longer follow-up.