Association Between Stimulant Treatment and Substance Use Through Adolescence Into Early Adulthood.

Importance: Possible associations between stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) and subsequent substance use remain debated and clinically relevant. Objective: To assess the association of stimulant treatment of ADHD with subsequent substance use using the Multimodal Treatment Study of ADHD (MTA), which provides a unique opportunity to test this association while addressing methodologic complexities (principally, multiple dynamic confounding variables). Design, Setting, and Participants: MTA was a multisite study initiated at 6 sites in the US and 1 in Canada as a 14-month randomized clinical trial of medication and behavior therapy for ADHD but transitioned to a longitudinal observational study. Participants were recruited between 1994 and 1996. Multi-informant assessments included comprehensively assessed demographic, clinical (including substance use), and treatment (including stimulant treatment) variables. Children aged 7 to 9 years with rigorously diagnosed DSM-IV combined-type ADHD were repeatedly assessed until a mean age of 25 years. Analysis took place between April 2018 and February 2023. Exposure: Stimulant treatment of ADHD was measured prospectively from baseline for 16 years (10 assessments) initially using parent report followed by young adult report. Main Outcomes and Measures: Frequency of heavy drinking, marijuana use, daily cigarette smoking, and other substance use were confidentially self-reported with a standardized substance use questionnaire. Results: A total of 579 children (mean [SD] age at baseline, 8.5 [0.8] years; 465 [80%] male) were analyzed. Generalized multilevel linear models showed no evidence that current (B [SE] range, -0.62 [0.55] to 0.34 [0.47]) or prior stimulant treatment (B [SE] range, -0.06 [0.26] to 0.70 [0.37]) or their interaction (B [SE] range, -0.49 [0.70] to 0.86 [0.68]) were associated with substance use after adjusting for developmental trends in substance use and age. Marginal structural models adjusting for dynamic confounding by demographic, clinical, and familial factors revealed no evidence that more years of stimulant treatment (B [SE] range, -0.003 [0.01] to 0.04 [0.02]) or continuous, uninterrupted stimulant treatment (B [SE] range, -0.25 [0.33] to -0.03 [0.10]) were associated with adulthood substance use. Findings were the same for substance use disorder as outcome. Conclusions and Relevance: This study found no evidence that stimulant treatment was associated with increased or decreased risk for later frequent use of alcohol, marijuana, cigarette smoking, or other substances used for adolescents and young adults with childhood ADHD. These findings do not appear to result from other factors that might drive treatment over time and findings held even after considering opposing age-related trends in stimulant treatment and substance use.

Adult substance use as a function of growth in peer use across adolescence and young adulthood in the context of ADHD: Findings from the MTA.

Peer substance use strongly predicts adolescent and young adult substance use, but its role in ADHD-related risk for substance use, especially in adulthood, is unclear. In a sample with (n = 516) and without (n = 249) childhood ADHD from the Multimodal Treatment Study of ADHD, we compared associations between change over time in peer substance use and personal substance use (alcohol, cigarettes, marijuana, illicit drugs) from age 14-26 by ADHD status. Developmentally typical peer substance use trajectories across adolescence and young adulthood coincided with similar changes in personal use - but less so for those with ADHD histories. Concurrent associations between peer and personal use in adolescence and young adulthood were weaker for those with ADHD histories than without for commonly used substances (alcohol, marijuana). Prospectively, escalating peer use during adolescence forecasted adulthood declines for commonly used substances, yet persistently high substance use at age 25, regardless of ADHD history. In the reverse direction, growth in adolescent substance use predicted developmentally normative young adult declines in peer use - but for the ADHD group, adolescent heavy drinking predicted increases in young adult peer use. Findings suggest that individuals with ADHD may have difficulty emulating their peers' developmentally normative declines in substance use, highlighting the importance of social factors when treating young adults affected by ADHD and substance abuse.