Antipsychotic medication and the prevention of psychiatric emergencies in difficult-to-treat adolescent depression.

OBJECTIVES: It is unclear how antipsychotic medications affect acute healthcare use among adolescents with depression. We compared risk of psychiatric emergencies between adolescents with difficult-to-treat depression initiating new antipsychotic versus antidepressant medications. METHODS: This cohort study employed a target trial emulation framework using Optum's de-identified Clinformatics® Data Mart Database between 2009 and 2021. We compared risk of emergency visits or inpatient encounters with mental health diagnoses (i.e. psychiatric emergencies) following new atypical antipsychotic versus secondary antidepressant prescription fills among adolescents (10-19 years old) with depression. All adolescents had filled SSRI prescriptions within one year prior to initiating a secondary medication and had no FDA-approved indications for pediatric antipsychotic use. RESULTS: Among youth with depression and SSRI receipt, there were 3710 incident antipsychotic users (63.7% female) and 28,527 secondary antidepressant users (71.7% female). Within 1 year of initiation, antipsychotic medications were associated with a higher risk of psychiatric emergencies (propensity-score weighted HR = 1.59; 95% CI = 1.46, 1.72) compared with secondary antidepressant medications. The weighted cumulative incidence of psychiatric emergencies was 38.7% (95% CI = 34.8%, 42.7%) for antipsychotic and 24.5% (95% CI = 23.7%, 25.3%) for secondary antidepressant users. Comparable results were observed for emergencies involving suicidality and in a series of sensitivity analyses. CONCLUSIONS: Our findings do not provide support for a protective effect of atypical antipsychotic medications compared with secondary antidepressant medications for the prevention of psychiatric emergencies in youth with difficult-to-treat depression.