Attention-Deficit/Hyperactivity Disorder Treatment Patterns and Association With Clinical Outcomes in Adolescents and Young Adults with Co-Occurring Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder: A Retrospective Analysis

Objective: This study evaluated the impact of co-occurring substance use disorder (SUD) on attention-deficit/hyperactivity disorder (ADHD) treatment patterns and examined clinical outcomes associated with ADHD treatment in adolescents and young adults with both ADHD and SUD. Method: This retrospective cohort study used TriNetX US Collaborative Network data on 1.23 million individuals 15 to 25 years of age who were diagnosed with ADHD from 2007 to 2024. About 23% (n = 288,159) had co-occurring SUD. Prescription patterns for ADHD medications and associated clinical outcomes were analyzed over 1 year. Relative risks (RRs), hazard ratios (HRs), and 95% CIs were calculated using propensity score matching and Cox proportional hazards models to adjust for confounders. Results: Central nervous system (CNS) stimulant prescriptions were less frequent in the ADHD with SUD cohort (RR = 0.63, 95% CI = 0.62-0.63), whereas new bupropion prescriptions were slightly more frequent (RR = 1.05, 95% CI = 1.02-1.08) compared with ADHD without SUD. In ADHD with SUD, ADHD treatment (including prescriptions for CNS stimulants and nonstimulants) was associated with fewer hospitalizations, reduced emergency care, lower risk of suicidal ideation/attempts (range of RRs = 0.74-0.82), and continuous use of psychiatric services (RR = 1.23), but fewer methadone prescriptions (RR = 0.74). Compared with nonstimulants, stimulant treatment was associated with fewer hospitalizations, accidental overdoses, and suicidal ideation/attempts (range of RRs = 0.63-0.79). Overall, ADHD treatment was associated with a 30% lower risk of mortality (aHR = 0.70, 95% CI = 0.65-0.75). Conclusion: Clinicians appear to be hesitant to prescribe CNS stimulants in the context of SUD; however, these findings align with clinical trials suggesting potential benefits of ADHD medication for individuals with co-occurring SUD. Bridging the gap between clinical practice and the evidence base will require ongoing research, clinician education, and policy change. Plain language summary: This study examined how treatment patterns and outcomes for adolescents and young adults co-occurring attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD). The authors conducted a retrospective cohort study using TriNetX US Collaborative Network data (N = 288,159 youths with ADHD and a co-occurring SUD). Adolescents and young adults with both conditions were less likely to receive ADHD medication, particularly stimulants. However, ADHD treatment was associated with fewer hospitalizations, lower risk of intubation, and reduced mortality. Across multiple outcomes, stimulant medications demonstrated more favorable clinical outcomes than nonstimulants, suggesting potential benefits of certain ADHD medications for individuals with co-occurring SUD.