Metabolic adverse events associated with antipsychotic polypharmacy versus monotherapy among new pediatric users

Purpose: Limited information is available on antipsychotic polypharmacy and associated metabolic adverse events in a pediatric population.This study sought to determine the risk of metabolic adverse events associated with antipsychotic polypharmacy compared to antipsychotic monotherapy use among commercially insured pediatric antipsychotic users.Methods: This was a retrospective cohort study of commercial health plans claims data.New users of antipsychotic medication(s) aged 1-17 years on the date of the first antipsychotic prescription were selected and followed for up to one year after antipsychotic initiation.Patients with preexisting metabolic conditions were excluded.Antipsychotic polypharmacy was defined as concurrent use of two or more chemically distinctive antipsychotic agents.Metabolic adverse events were captured using diagnosis or medication use during the one-year post-index period.Survival analyses using Cox regression models with time-varying exposure variables (any antipsychotic use, antipsychotic dose, antipsychotic exposure-dose combination and antipsychotic type) were conducted adjusting for baseline patient demographic and clinical characteristics.Results: The study included 3,038 pediatric patients with antipsychotic use and 11.06% of them received antipsychotic polypharmacy during the one-year follow-up period.Compared to monotherapy, no statistically significant effect of antipsychotic polypharmacy was found for metabolic adverse events However, high total daily dose of antipsychotics was found to be significantly associated with metabolic adverse events (HR: 2.42 CI: 1.35-4.32). Conclusion:Although no clear increase in risk of metabolic adverse events were detected for antipsychotic polypharmacy use compared to monotherapy, high daily dose of total antipsychotic use was associated with elevated risk for metabolic adverse events in pediatric patients.