Combined pharmacotherapies and behavioral interventions for alcohol dependence (The COMBINE Study): examination of posttreatment drinking outcomes

J Stud Alcohol Drugs. 2008 Jan;69(1):5-13. doi: 10.15288/jsad.2008.69.5.


Objective: The aim of this study was to examine the efficacy of pharmacological and behavioral interventions across 1 year posttreatment in the COMBINE (Combining Medications and Behavioral Interventions) Study.

Method: Alcohol-dependent individuals (N = 1,383; 428 women) recruited at 11 outpatient academic alcoholism-treatment clinics across the United States participated in a randomized, double-blind, placebo-controlled trial. They received 16 weeks of naltrexone (Revia) or acamprosate (Campral) or both medications and/or placebos in combination with medical management (MM), with or without combined behavioral intervention (CBI); one group received CBI without pills or MM. Drinking behavior and clinical status were assessed at the end of treatment (Week 16) and at Weeks 26, 52, and 68.

Results: Prior treatment with active naltrexone, without active acamprosate or CBI or with active acamprosate plus CBI, and CBI with double placebo resulted in a significantly higher percentage of days abstinent than double placebos with no CBI (p < .05). Having received CBI was associated with positive clinical response posttreatment, compared with not having received CBI. Prior treatment with naltrexone increased the time to the first heavy-drinking day posttreatment (p = .03). No differences were found between patients who had received CBI without MM or pills and those having received MM and double placebo with or without CBI. No significant main effects for acamprosate were found on any of the outcome measures.

Conclusions: Previous treatment with MM and either CBI or naltrexone, or both, but not acamprosate, was associated with sustained efficacy beyond discontinuation. Reasons for the maintained treatment gains with naltrexone and/or CBI and potential methods to extend them are discussed.

Publication types

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

MeSH terms

  • Acamprosate
  • Adult
  • Aged
  • Alcohol Deterrents / therapeutic use*
  • Alcoholism / drug therapy
  • Alcoholism / therapy*
  • Cognitive Behavioral Therapy / methods*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Taurine / analogs & derivatives*
  • Taurine / therapeutic use
  • Treatment Outcome


  • Alcohol Deterrents
  • Taurine
  • Acamprosate