Do patients with alcohol dependence respond to placebo? Results from the COMBINE Study

J Stud Alcohol Drugs. 2008 Nov;69(6):878-84. doi: 10.15288/jsad.2008.69.878.


Objective: The purpose of this study was to examine the nature of the effect of placebo medication plus accompanying medical management in the treatment of alcohol dependence.

Method: The National Institute on Alcohol Abuse and Alcoholism COMBINE (Combining Medications and Behavioral Interventions) study, a randomized controlled double-blind trial of 1,383 alcohol-dependent patients, compared combinations of medications (acamprosate [Campral] and naltrexone [ReVia]) and behavioral therapy (medical management and specialist-delivered behavioral therapy) for alcohol dependence. This report focuses on a subset of that study population (n = 466) receiving (1) specialized behavioral therapy alone (without pills), (2) specialized behavioral therapy + placebo medication + medical management, or (3) placebo + medical management.

Results: During 16 weeks of treatment, participants receiving behavioral therapy alone had a lower percentage of days abstinent (66.6%) than did the participants receiving placebo and medical management (73.1%) or those receiving specialized behavioral therapy + placebo + medical management (79.4%). The group receiving behavioral therapy alone relapsed to heavy drinking more often (79.0%) than those receiving behavioral therapy + placebo + medical management (71.2%). This report focuses on potential explanations for this finding. The two groups of participants receiving placebo + medical management were more likely to attend Alcoholics Anonymous meetings during treatment (32.7% and 32.0% vs 20.4%) and were less likely to withdraw from treatment (14.1% and 22.9% vs 29.3%).

Conclusions: There appeared to be a significant "placebo effect" in the COMBINE Study, consisting of pill taking and seeing a health care professional. Contributing factors to the placebo response may have included pill taking itself, the benefits of meeting with a medical professional, repeated advice to attend Alcoholics Anonymous, and optimism about a medication effect.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acamprosate
  • Adult
  • Alcohol Deterrents / therapeutic use*
  • Alcoholics Anonymous
  • Alcoholism / psychology
  • Alcoholism / rehabilitation
  • Alcoholism / therapy*
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Naltrexone / therapeutic use
  • Narcotic Antagonists / therapeutic use
  • Negativism
  • Placebo Effect
  • Secondary Prevention
  • Taurine / analogs & derivatives
  • Taurine / therapeutic use
  • Temperance / psychology
  • Treatment Outcome


  • Alcohol Deterrents
  • Narcotic Antagonists
  • Taurine
  • Naltrexone
  • Acamprosate