Pediatric Off-label Antipsychotic Use for Attention-Deficit/Hyperactivity Disorder.

Purpose: Off-label antipsychotic use for behavioral symptoms in pediatric attention-deficit/hyperactivity disorder (ADHD) poses safety concerns, and evidence to support such use is limited. This study aims to investigate the risk of off-label antipsychotic use associated with comorbid disruptive behavior disorder (DBD) among a cohort of youth with ADHD.

Methods: A cohort study was conducted using IQVIA PharMetrics Plus for Academics data from 2007 to 2020. Youth 5 to 15 years of age at the index ADHD visit were included in the cohort. The index ADHD visit meets at least 1 of the following criteria: (1) 1 inpatient ADHD visit, (2) 2 outpatient ADHD visits within 90 days, or (3) an ADHD medication prescription fill within 30 days of an outpatient ADHD visit. We excluded youth who had a diagnosis of DBD or a US Food and Drug Administration (FDA)-approved indication for antipsychotics at baseline. Youth were followed up until antipsychotic initiation or were censored at a loss of coverage, receipt of an FDA-indicated diagnosis, or end of the study. A Cox proportional hazards regression model with DBD as a time-varying covariate estimated the hazard of antipsychotic use after the index ADHD visit.

Findings: Of 41,098 youth with ADHD who met the study criteria, 4557 were diagnosed with DBD during follow-up. The incidence of antipsychotic initiation was 19.6 (95% CI, 18.7- 20.5) per 1000 person-years. After adjustment for baseline covariates, the hazard ratio of antipsychotic initiation associated with DBD was 4.64 (95% CI, 4.15-5.18).

Implications: Antipsychotic use among youth with ADHD is more likely in the presence of DBD, suggesting that an off-label use is for behavior problems.