Correlates of alcohol use in adults with ADHD and comorbid alcohol use disorders: exploratory analysis of a placebo-controlled trial of atomoxetine

Abstract

Background:

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorder are often comorbid in adults. The effects of ADHD treatment on comorbid alcohol use disorder have not been extensively studied.

Objective:

To assess correlates of ADHD and alcohol use outcomes in ADHD with comorbid alcohol use disorders, via a post-hoc exploratory subgroup analysis of a previously conducted, randomized, double-blind, placebo-controlled study of recently abstinent adults.

Methods:

Adults who had ADHD and alcohol use disorders and were abstinent for 4–30 days were randomized to daily atomoxetine 25–100 mg (mean final dose = 89.9 mg) or placebo for 12 weeks. Changes in ADHD symptoms from baseline to endpoint were assessed using the ADHD Investigator Symptom Rating Scale (AISRS) total score, alcohol use by the timeline followback method, and alcohol cravings by the Obsessive Compulsive Drinking Scale.

Results:

Of 147 subjects receiving atomoxetine (n = 72) or placebo (n = 75) in the primary study, 80 (54%) completed 12 weeks (n = 32 atomoxetine; n = 48 placebo). Improvements in ADHD symptoms on the AISRS correlated significantly with decreases in alcohol cravings (Pearson’s r = 0.28; 95% confidence interval [CI] = 0.11–0.43; p = 0.002), and the correlation was most notable with atomoxetine (r = 0.29; CI [0.04 – 0.51]; p = 0.023) rather than with placebo (r = 0.24; CI [0.00–0.46]; p = 0.055). On-treatment drinking levels correlated with AISRS scores (r = 0.12; CI [0.05 –0.19]; p = 0.001). Relapse to alcohol abuse significantly correlated with worse ADHD symptoms on 15 of 18 items of the AISRS in the placebo group (p < 0.05 for each).

Conclusions:

No baseline predictor (other than degree of sobriety) of alcohol use or ADHD outcomes emerged. ADHD symptom improvements correlated significantly with reductions in alcohol cravings, and relapse to alcohol abuse correlated significantly with worsening of most ADHD symptoms in the placebo group, but not in the atomoxetine group. This post-hoc subgroup analysis is of a hypothesis-generating nature, and the generalizability of the findings may be limited by exclusion of adults with common ADHD comorbidities from the base study. Further, prospective clinical trials in larger and more heterogeneous patient populations are warranted to confirm or reject these preliminary associations.

Trial registration: ClinicalTrials.gov identifier: NCT00190957.

Key words::

• Adult
• Alcohol
• Atomoxetine
• Attention-deficit/hyperactivity disorder
• Drug therapy
• Treatment outcomes

Transparency

Declaration of funding

This study and the present communication were supported by Eli Lilly and Co. (Indianapolis, IN, USA) and a National Institute on Drug Abuse grant to T.E.W. (#K24 DA016264).

Declaration of financial/other relationships

T.E.W. has disclosed that he receives or has received grant support from the following sources: Abbott, McNeil, Lilly, Nextwave, National Institutes of Health/National Institute of Drug Addiction (NIH/NIDA), Merck, and Shire; has been a speaker for Lilly, McNeil, Novartis, and Shire; and is or has been a consultant for Abbott, AstraZeneca, McNeil, Lilly, Nextwave, NIH, Novartis, Merck, and Shire. T.E.W. has a published book with Guilford Press: Straight Talk About Psychiatric Medications for Kids. L.A.A. has disclosed that, in the past 3 years, he has received grant/research support from Abbott, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Shire, Lilly, Ortho-McNeil/Janssen/Johnson & Johnson, New River Pharmaceuticals, Cephalon, NIDA, Chelsea Therapeutics, and Organon; served on advisory boards and as a consultant to Abbott, Cortex Pharmaceuticals, Novartis, Pfizer, Shire, Lilly, Ortho McNeil/Janssen/Johnson & Johnson, Merck, Organon, sanofi-aventis, Psychogenics, Mindsite (uncompensated), AstraZeneca, Major League Baseball, and i3 Research; and has served as a consultant to Epi-Q, INC Research, United BioSource, Otsuka, and the Major League Baseball Players Association. L.A.A. has served on speakers bureaus for Shire, Ortho-McNeil/Janssen/Johnson & Johnson, and Lilly (but does not currently serve on any speakers bureaus) and has received royalty payments (as inventor) from NYU for license of adult ADHD scales and training materials. He has no stock ownership. Y.T. and H.P.U. are employees of and shareholders in Lilly. F.X. and D.N.D. are paid consultants to Lilly and/or its affiliates. When the study was conducted and early drafts of the manuscript prepared, D.N.D. was an employee of, and minor shareholder in, the study sponsor. S.W.G. is a paid consultant to Lilly (and its affiliates) and BioBehavioral Diagnostics (Westford, MA, and Plymouth Meeting, PA, USA).

Acknowledgments

Editorial assistance was provided by Ann C. Sherwood, PhD, and Lauren Baker, PhD, Rete Biomedical Communications Corp. (Wyckoff, NJ), with financial support from Eli Lilly and Co.

Author contributions – category 1 (a) conception and design: T.E.W, L.A.A., H.P.U. (b) Acquisition of data: T.E.W., L.A.A., and other clinical investigators. (c) Analysis and interpretation of data: all authors. Category 2 (a) drafting the article: T.E.W. drafted the initial outline and manuscript. S.W.G. further revised the manuscript draft and provided further editorial assistance along with Ann C. Sherwood, PhD, and Lauren Baker, PhD (Rete Biomedical Communications Corp., Wyckoff, NJ, USA). (b) Revising it for intellectual content: all authors. Category 3 (a) final approval of the completed article: All authors.

Study guarantor: T.E.W. had been involved in the design and training of the original trial, has had access to all data, drafted and edited the manuscript, and takes responsibility for the study.

Previous presentation: selected findings were presented at the 57th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, New York, NY, October 26–31, 2010.