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Adolescent Substance Use in the Multimodal Treatment Study of Attention-Deficit/Hyperactivity Disorder (ADHD) (MTA) as a Function of Childhood ADHD, Random Assignment to Childhood Treatments, and Subsequent Medication

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Objective

To determine long-term effects on substance use and substance use disorder (SUD), up to 8 years after childhood enrollment, of the randomly assigned 14-month treatments in the multisite Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA; n = 436); to test whether medication at follow-up, cumulative psychostimulant treatment over time, or both relate to substance use/SUD; and to compare substance use/SUD in the ADHD sample to the non-ADHD childhood classmate comparison group (n = 261).

Method

Mixed-effects regression models with planned contrasts were used for all tests except the important cumulative stimulant treatment question, for which propensity score matching analysis was used.

Results

The originally randomized treatment groups did not differ significantly on substance use/SUD by the 8-year follow-up or earlier (mean age = 17 years). Neither medication at follow-up (mostly stimulants) nor cumulative stimulant treatment was associated with adolescent substance use/SUD. Substance use at all time points, including use of two or more substances and SUD, were each greater in the ADHD than in the non-ADHD samples, regardless of sex.

Conclusions

Medication for ADHD did not protect from, or contribute to, visible risk of substance use or SUD by adolescence, whether analyzed as randomized treatment assignment in childhood, as medication at follow-up, or as cumulative stimulant treatment over an 8-year follow-up from childhood. These results suggest the need to identify alternative or adjunctive adolescent-focused approaches to substance abuse prevention and treatment for boys and girls with ADHD, especially given their increased risk for use and abuse of multiple substances that is not improved with stimulant medication.

Clinical trial registration information—Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA); http://clinical trials.gov/; NCT00000388.

Section snippets

Participants

The participants with ADHD in the MTA were 579 children with DSM-IV ADHD combined type. Each of the six participating sites randomized 95 to 98 children to one of four treatment groups: Medication Management (MedMgt), Behavior Therapy (Beh), Combined MedMgt plus Beh (Comb), and Community Comparison (CC). At baseline (pretreatment), participants were 7.0 to 9.9 years of age (mean = 8.5 years, SD = 0.8 years). The MTA recruitment strategy, procedures for diagnosing ADHD, treatment specifics, and

Medication Use Over Time

To explicate the medication variable, we first examined medication use over time. As previously reported, proportion of days medicated in the past year declined over time to mean = 0.31(SD = 0.42) by the 8-year follow-up. In contrast, at 14 months, when study-delivered treatment ended, the mean (SD) was 0.71 (0.22) for Comb; 0.71 (0.24) for MedMgt; 0.54 (0.41) for CC; and 0.16 (0.28) for Beh. At the 8-year follow-up, only 32.5% (132/406 with complete medication data) were medicated more than

Discussion

The current study first tested the hypothesis that children with combined type ADHD have increased risk of substance use and SUD in adolescence. We found a significantly higher prevalence of substance use by adolescents with, versus former classmates without, ADHD histories. Overall group differences for any SUD (DSM-IV abuse or dependence) were also observed, but these occurred at comparatively lower rates and only at certain ages—for marijuana and nicotine only—highlighting the importance of

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    • Cited by (0)

    The work reported was supported by cooperative agreement grants and contracts from NIMH and the National Institute on Drug Abuse (NIDA) to the following: University of California–Berkeley: U01 MH50461, N01MH12009, and HHSN271200800005-C; DA-8-5550; Duke University: U01 MH50477, N01MH12012, and HHSN271200800009-C; DA-8-5554; University of California–Irvine: U01 MH50440, N01MH 12011, and HHSN271200800006-C; DA-8-5551; Research Foundation for Mental Hygiene (New York State Psychiatric Institute/Columbia University): U01 MH50467, N01 MH12007, and HHSN271200800007-C; DA-8-5552; Long Island–Jewish Medical Center U01 MH50453; New York University: N01MH 12004, and HHSN271200800004-C; DA-8-5549; University of Pittsburgh: U01 MH50467, N01 MH 12010, and HHSN 271200800008C; DA-8-5553; and McGill University N01MH12008, and HHSN271200800003-C; DA-8-5548. The Office of Special Education Programs of the U.S. Department of Education, the Office of Juvenile Justice and Delinquency Prevention of the Justice Department, and NIDA also participated in funding.

    Drs. Gibbons, Howard, Hur, Lu, and Marcus served as the statistical experts for this research.

    This article is discussed in an editorial by Dr. Benjamin I. Goldstein on page 225.

    The Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD) (MTA) was an NIMH cooperative agreement randomized clinical trial involving six clinical sites. Collaborators from NIMH: Peter S. Jensen, M.D., of the Mayo Clinic; L. Eugene Arnold, M.D., M.Ed., of Ohio State University; Joanne B. Severe, M.S., of the Clinical Trials Operations and Biostatistics Unit, Division of Services and Intervention Research; Benedetto Vitiello, M.D., of the Child and Adolescent Treatment and Preventive Interventions Research Branch; Kimberly Hoagwood, Ph.D., of Columbia University; previous contributors from NIMH to the early phase: John Richters, Ph.D., of the National Institute of Nursing Research; and Donald Vereen, M.D., of NIDA. Principal investigators and co-investigators from the clinical sites are: University of California–Berkeley/San Francisco: Stephen P. Hinshaw, Ph.D., of Berkeley; and Glen R. Elliott, Ph.D., M.D., of San Francisco; Duke University: C. Keith Conners, Ph.D.; Karen C. Wells, Ph.D.; John March, M.D., M.P.H.; and Jeffery Epstein, Ph.D.; University of California–Irvine/Los Angeles: James Swanson, Ph.D., of Irvine; Dennis P. Cantwell, M.D., deceased, of Los Angeles; and Timothy Wigal, Ph.D., of Irvine; Long Island Jewish Medical Center/Montreal Children's Hospital: Howard B. Abikoff, Ph.D., of New York University School of Medicine; and Lily Hechtman, M.D., McGill University; New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center: Laurence L. Greenhill, M.D., of Columbia University; and Jeffrey H. Newcorn, M.D., of Mount Sinai School of Medicine; University of Pittsburgh: William E. Pelham, Ph.D., of Florida International University; Betsy Hoza, Ph.D., of the University of Vermont; and Brooke Molina, Ph.D. Original statistical and trial design consultant: Helena C. Kraemer, Ph.D., of Stanford University. Follow-up phase statistical collaborators: Robert D. Gibbons, Ph.D., of the University of Illinois–Chicago; Sue Marcus, Ph.D., of Mt. Sinai College of Medicine; and Kwan Hur, Ph.D., of the University of Illinois–Chicago. Collaborator from the Office of Special Education Programs/US Department of Education: Thomas Hanley, Ed.D. Collaborator from Office of Juvenile Justice and Delinquency Prevention/Department of Justice: Karen Stern, Ph.D.

    The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health (NIH), or NIMH.

    Disclosure: Dr. Hinshaw has received an honorarium from the American Psychological Association for his editorship of Psychological Bulletin. Dr. Arnold has received research funding from Curemark, Eli Lilly and Co., and Shire; advisory board honoraria from Biomarin, Noven, Seaside Therapeutics, and Shire; and travel support from Noven. Dr. Swanson has served on the advisory board of Noven Pharmaceuticals, and has received travel support from Shire and Jannsen to attend separate, professional meetings. Dr. Pelham has received a research grant from and has served on the advisory board of Noven Pharmaceuticals. Dr. Hechtman has received research funds from and has served on the advisory boards and speakers’ bureaus for Eli Lilly and Co., Janssen, Ortho, Purdue, and Shire. Dr. Wigal has received research support and consulting honoraria from, and has served on the speakers’ bureau for Eli Lilly and Co., Noven, Rhodes, Otsuka, and Shire. Dr. Abikoff has received royalties from Multi-Health Systems regarding the Children’s Organizational Skills Scale. Dr. Greenhill has received grant support from Shire and Rhodes, and has served as a member of the Scientific Advisory Board of BioBDX LLC. Dr. Jensen has received honoraria for three keynote addresses given at European conferences on attention-deficit/hyperactivity disorder treatment outcomes (two from Shire and one from Janssen-Cilag), and has received a charitable donation from Shire. Dr. Wells has received royalties from Multi-Health Systems, the publisher of Conners’ Rating Scales. Drs. Molina, Hoza, Epstein, Vitiello, Gibbons, Howard, Hur, Lu, and Marcus, and Ms. Houck report no biomedical financial interests or potential conflicts of interest.

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