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Randomized Controlled Trial
. 2023 Sep 1;80(9):933-941.
doi: 10.1001/jamapsychiatry.2023.2157.

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

Brooke S G Molina  1 , Traci M Kennedy  2 , Andrea L Howard  3 , James M Swanson  4 , L Eugene Arnold  5 , John T Mitchell  6 , Annamarie Stehli  4 , Edward H Kennedy  7 , Jeffery N Epstein  8 , Lily T Hechtman  9 , Stephen P Hinshaw  10 , Benedetto Vitiello  11
Affiliations
Randomized Controlled Trial

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

Brooke S G Molina et al. JAMA Psychiatry. .

Erratum in

  • Error in Key Points.
    [No authors listed] [No authors listed] JAMA Psychiatry. 2023 Sep 1;80(9):972. doi: 10.1001/jamapsychiatry.2023.3120. JAMA Psychiatry. 2023. PMID: 37672045 Free PMC article. No abstract available.

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Molina reported grants from the National Institute of Mental Health and National Institute on Drug Abuse during the conduct of the study. Dr Howard reported grants from National Institute on Drug Abuse during the conduct of the study. Dr Swanson reported honoraria, consulting fees, and support for travel to and presentations at professional meetings by Medice, NLS, and Takeda; a patent for Pixel Averages for Auxological Assessment (PIXA); a patent pending for Prevention of Accumulated Tolerance for Stimulant Medication for Treatment of ADHD (PATSMTA); and previous but not current or recent support from grants and contracts for studies of treatment of attention-deficit/hyperactivity disorder. Dr Arnold reported grants from Axial, Yamo, Myndlift, Maplight, and Foundation for MH Research and personal fees from CHADD outside the submitted work. Dr Mitchell reported royalties from Guilford Press; sponsored research from Lumos Labs Industry; consulting for Akili Interactive and Keller Postman LLC; and grants from Templeton Foundation, and Duke Children’s Health and Discovery Initiative/Duke Clinical and Translational Science Institute outside the submitted work. Dr Epstein reported grants from Akili Interactive Labs, National Institutes of Health, and Agency for Healthcare and Research Quality and personal fees from Multi-Health Systems and American Psychological Association outside the submitted work. Dr Vitiello reported consultant fees or honoraria from Medice Pharmaceuticals, Alkermes Pharmaceuticals, Menarini Pharmaceuticals, and Angelini Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Rates of Stimulant and Substance Use at the 2-Year Through 16-Year Follow-up Assessments of the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder
See this image and copyright information in PMC

References

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