Testing combined pharmacotherapies and behavioral interventions for alcohol dependence (the COMBINE study): a pilot feasibility study

Alcohol Clin Exp Res. 2003 Jul;27(7):1123-31. doi: 10.1097/01.ALC.0000078020.92938.0B.

Abstract

Background: Medications (such as naltrexone and acamprosate) as well as behavioral therapies have been previously reported to be effective in the reduction of alcohol intake and to prevent relapse drinking. However, the efficacy of using several medications alone or together in combination with behavioral therapies has not been widely investigated. The purpose of this study was to evaluate the feasibility of this combined therapy approach to apply it to a larger scale multisite clinical trial. Outcome focused on recruitment, retention, adherence to study parameters and medication, physical complaints, and physiologic toxicity.

Methods: At 11 sites, 108 individuals with alcohol dependence were randomized in a double blind fashion to receive placebo, naltrexone, or acamprosate alone or in combination. In addition, some individuals were randomized to receive Medical Management (MM) provided by a health care practitioner alone or in combination with an enhanced behavioral intervention, Combined Behavioral Intervention (CBI), delivered by a trained therapist. A final group received CBI alone without pills. All participants were treated and assessed for a maximum of 16 weeks.

Results: The attendance at therapy and research visits, and medication adherence and tolerability were good with no statistical differences between the medication or behavioral intervention groups. Over 75% of participants completed the week-16, end of study, assessment and the average medication adherence (percent of total pills taken) was about 65%. The level and types of physical complaints were not unexpected and similar among the medication and placebo groups. There were no group differences in liver or kidney toxicity. Importantly, the combination of naltrexone and acamprosate did not present significantly more physical complaints than either alone.

Conclusions: Sufficient numbers of alcohol dependent participants can be recruited and retained in a relatively sophisticated outpatient trial combining medications and behavioral interventions. Participant adherence to the trial protocol including medication regimens was at acceptable levels. Physical complaints and organ toxicity were within expected and acceptable levels. Based on these results a larger scale study utilizing these methodologies appears feasible.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acamprosate
  • Adult
  • Alcoholism / drug therapy*
  • Alcoholism / epidemiology*
  • Alcoholism / therapy
  • Behavior Therapy / methods*
  • Behavior Therapy / statistics & numerical data
  • Double-Blind Method
  • Drug Therapy, Combination
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naltrexone / adverse effects
  • Naltrexone / therapeutic use
  • Pilot Projects
  • Taurine / adverse effects
  • Taurine / analogs & derivatives*
  • Taurine / therapeutic use

Substances

  • Taurine
  • Naltrexone
  • Acamprosate