AbstractPurposeTo examine trends in off‐label antipsychotic use for youth with attention‐deficit/hyperactivity disorder with and without a comorbid disruptive behavior disorder.MethodThis cross‐sectional study of annual trends from 2007 through 2015 used the IQVIA PharMetrics® Plus for Academics data. We identified 165 794 commercially‐insured youth 3–18‐year‐old who had a diagnosis of attention‐deficit/hyperactivity disorder and classified them into subgroups with and without disruptive behavior disorders comorbidities. Antipsychotic use, with or without a stimulant, was the primary dependent outcome. Logistic regression estimated the odds of antipsychotic use associated with comorbid attention‐deficit/hyperactivity disorder and disruptive behavior disorders, adjusting for age, sex, study year, and other psychotropic use.ResultsOver 70% of the 165 794 youth with attention‐deficit/hyperactivity disorder were 5–14‐year‐old and male, and 12% had disruptive behavior disorders. Antipsychotic prevalence, with or without a stimulant, was 4.4% in 2007 and 3.4% in 2015. Stimulants with antipsychotics increased significantly from 2007 to 2015 for females (19.5%–28.7%) and youth 15–18‐year‐old (25.9%–32.7%). Adjusting for age, sex, study year, and other psychotropic use, youth with a comorbid disruptive behavior had a 2.5 (95% CI: 2.3, 2.7) higher likelihood of receiving an antipsychotic than youth with attention‐deficit/hyperactivity disorder and no comorbidities.ConclusionsAntipsychotic use was associated with comorbid disruptive behaviors in youth with attention‐deficit/hyperactivity disorder. Off‐label antipsychotic use has increased for females and older adolescents.