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Placebo Group Improvement in Trials of Pharmacotherapies for Alcohol Use Disorders: A Multivariate Meta-Analysis Examining Change Over Time

Del Re, A. C. PhD; Maisel, Natalya PhD; Blodgett, Janet C. MA; Wilbourne, Paula PhD; Finney, John W. PhD

Journal of Clinical Psychopharmacology: October 2013 - Volume 33 - Issue 5 - p 649–657
doi: 10.1097/JCP.0b013e3182983e73
Original Contributions

Objective Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement.

Method Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment.

Results Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time.

Conclusions Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.

Supplemental digital content is available in the text.

From the VA Palo Alto Health Care System, Menlo Park; and Stanford University Medical School, Stanford, CA.

Received April 18, 2012; accepted after revision November 28, 2012.

Reprints: A. C. Del Re, PhD, HSR&D Center for Health Care Evaluation, Stanford University Medical School, VA Palo Alto Health Care System (152MPD), 795 Willow Rd, Menlo Park, CA 94025 (e-mail:

Preparation of this manuscript was supported by the US National Institute on Alcohol Abuse and Alcoholism Grant AA008689 and the US Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service and Substance Use Disorder Quality Enhancement Research Initiative. The views expressed are those of the authors and do not necessarily represent the views of the National Institute on Alcohol Abuse and Alcoholism, the Department of Veterans Affairs, or any other US Government entity.

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© 2013 by Lippincott Williams & Wilkins.