Association between tirzepatide use and risk of mortality, hospitalization, and suicidal behavior in patients with schizophrenia spectrum disorders: A one-year retrospective cohort study of 3618 patients.

This study aimed to evaluate the real-world effectiveness and psychiatric safety of tirzepatide among adults with schizophrenia spectrum disorders, focusing on the risks of mortality, hospitalization, and suicidal behavior. Based on the electronic health records from the TriNetX Global Collaborative Network, adults with schizophrenia spectrum disorders who initiated tirzepatide on or before June 1, 2024, were included. Tirzepatide users were propensity score-matched 1:1 to nonusers based on demographic and clinical variables. The primary outcome was a composite of all-cause mortality, hospitalization, and suicidal behavior evaluated between 30 and 365 days after the index date. Secondary outcomes included each component separately. Cox proportional hazards models and Kaplan-Meier estimators were used to estimate associations. Subgroup and sensitivity analyses were performed. Overall, a total of 1809 matched pairs were included. Tirzepatide use was associated with lower risk of the composite outcome (hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.55-0.79), as well as all-cause mortality (HR, 0.18; 95 % CI, 0.06-0.51), hospitalization (HR, 0.75; 95 % CI, 0.61-0.92), and suicidal behavior (HR, 0.43; 95 % CI, 0.27-0.70). Risk reduction was generally consistent across subgroups. Control outcome analyses supported internal validity. In conclusion, tirzepatide use in patients with schizophrenia spectrum disorders is associated with improved clinical outcomes, including reduced risks of mortality, hospitalization, and suicidal behavior. These findings support the integration of tirzepatide into metabolic management strategies for this high-risk population, offering benefits for glycemic control and potentially for psychiatric outcomes.