Background: Differences in survival between patients treated with antipsychotic monotherapy vs. polytherapy are debated. This study aimed to examine the association of antipsychotic polytherapy with 2-year all-cause mortality in a population-based cohort. Methods: Data were retrieved from healthcare databases of four local health units of Lombardy, Italy. Subjects aged 18-79 years who received continuous antipsychotic prescriptions in 2018 were identified. Overall survival among patients with antipsychotic monotherapy vs. polytherapy was compared. A multivariate Cox PH model was used to estimate the association between antipsychotic therapy, or antipsychotic use (continuous vs. non-continuous), and all-cause mortality. Adjustments were made for the presence of metabolic disturbances, total antipsychotic dosage amount (olanzapine equivalent doses), age, and sex. Results: A total of 49,875 subjects receiving at least one prescription of antipsychotics during 2018 were identified. Among the 33,221 patients receiving continuative antipsychotic prescriptions, 1958 (5.9%) experienced death from any cause at two years. Patients with continuous antipsychotic use had a 1.13-point increased mortality risk compared with non-continuous users. Patients treated with antipsychotic polytherapy showed an adjusted mortality risk increased by 17% (95% CI: 2%, 33%) compared to monotherapy. Conclusions: The study highlights the potential risks associated with antipsychotic polypharmacy, emphasizing the importance of optimizing drug prescriptions to improve patient safety and reduce mortality rates in individuals receiving antipsychotic therapy.
Keywords: all-cause mortality; antipsychotic monotherapy; antipsychotic polytherapy; drug safety; drug utilization research; metabolic side effects; pharmacoepidemiology.