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Timothy E. Wilens, Stephen V. Faraone, Joseph Biederman, and Samantha Gunawardene

Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature
Pediatrics 111: 179-185.

Russell A. Barkley, Mariellen Fischer, Lori Smallish, and Kenneth Fletcher

Does the Treatment of Attention-Deficit/Hyperactivity Disorder With Stimulants Contribute to Drug Use/Abuse? A 13-Year Prospective Study
Pediatrics 111: 97-109.

Abstract 1 of 2

Does Stimulant Therapy of Attention-Deficit/Hyperactivity Disorder Beget Later Substance Abuse? A Meta-analytic Review of the Literature

Timothy E. Wilens, MD^*,, Stephen V. Faraone, PhD^*,, Joseph Biederman, MD^*,, Samantha Gunawardene, BS^*

^* Clinical Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Boston, Massachusetts
Harvard Medical School, Boston, Massachusetts

--> Objective.Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes.

Methods.A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates.

Results.Six studies—2 with follow-up in adolescence and 4 in young adulthood—were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1–3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias.

Conclusion.Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders.

Key Words: attention-deficit/hyperactivity disorder • substance use • pharmacotherapy

Abbreviations: ADHD, attention-deficit/hyperactivity disorder • SUD, substance use disorders • OR, odds ratio • POR, precision of the odds ratio • SN, standard normal deviate • CI, confidence interval

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Abstract 2 of 2

Does the Treatment of Attention-Deficit/Hyperactivity Disorder With Stimulants Contribute to Drug Use/Abuse? A 13-Year Prospective Study

Russell A. Barkley, PhD^*, Mariellen Fischer, PhD, Lori Smallish, MA, Kenneth Fletcher, PhD^*

^* Department of Psychiatry, University of Massachusetts Medical School, Worcester, Massachusetts
Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin

--> Objective. To examine the impact of stimulant treatment during childhood and high school on risk for substance use, dependence, and abuse by young adulthood.

Methods. A total of 147 clinic-referred hyperactive children were followed approximately 13 years into adulthood (mean: 21 years old; range: 19–25). At adolescent (age 15) and adult follow-up, probands were interviewed about their use of various substances and duration of stimulant treatment.

Results. Duration of stimulant treatment was not significantly associated with frequency of any form of drug use by young adulthood. Stimulant-treated children had no greater risk of ever trying drugs by adolescence or any significantly greater frequency of drug use by young adulthood. Stimulant treatment in high school also did not influence drug use in adulthood except for greater use of cocaine. This difference was no longer significant after controlling for severity of attention-deficit/hyperactivity disorder and conduct disorder in childhood, adolescence, and adulthood. Stimulant treatment in either childhood or high school was not associated with any greater risk for any formal Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised drug dependence or abuse disorders by adulthood. Treatment with stimulants did not increase the risk of ever having tried most illegal substances by adulthood except for cocaine. Subsequent analyses showed that this elevated risk was primarily mediated by severity of conduct disorder by young adulthood and not by stimulant treatment in childhood.

Conclusion. This study concurs with 11 previous studies in finding no compelling evidence that stimulant treatment of children with attention-deficit/hyperactivity disorder leads to an increased risk for substance experimentation, use, dependence, or abuse by adulthood.

Key Words: hyperactivity • attention-deficit/hyperactivity disorder • stimulants • illicit drug use • drug abuse • conduct disorder

Abbreviations: ADHD, attention-deficit/hyperactivity disorder • CD, conduct disorder • SD, standard deviation • DSM, Diagnostic and Statistical Manual of Mental Disorders • CPRS-R, Conners Parent Rating Scale Revised • WWPARS, Werry-Weiss-Peters Activity Rating Scale • OR, odds ratio • SE, standard error

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