Combining Medication With Specialist Behavioral Intervention for Alcoholism: the COMBINE Study

To study the effects of pharmacotherapy with behavioral intervention for alcohol dependence, researchers randomized 1383 recently abstinent patients with alcoholism to 1 of 9 treatments for 16 weeks: placebo; naltrexone (100 mg per day), acamprosate (3 g per day), or both; or combined behavioral intervention (CBI)* alone, with active pills, or with placebo. All but the CBI alone group also received “medical management” (MM).** Follow-up was 94% at 16 weeks and 82% a year later.

• Drinking outcomes improved substantially in all groups. For example, the range of mean percent days abstinent across groups was 23%–30% at baseline, 67%– 81% at 16 weeks, and 59%–69% a year later.
• Key findings at 16 weeks include the following:
  • Naltrexone/MM was more effective than placebo/MM at increasing percent days abstinent (81% versus 75%) and delaying a return to heavy drinking*** (hazard ratio 0.7). Combining naltrexone/MM with CBI did not further improve these outcomes.
  • CBI/MM with active or placebo pills was also more effective than placebo/MM at increasing percent days abstinent (e.g., 79% versus 75%). However, CBI alone (without MM or pills) was less effective than placebo/MM (67% versus 74%).
  • Acamprosate did not significantly affect drinking outcomes.
• One year after treatment, drinking outcomes did not significantly differ among groups.

Comments:

This large, rigorous, and complex study showed that (1) naltrexone and specialist counseling have similar modest efficacy when each is offered with medical management, and (2) specialist counseling alone has less efficacy than when combined with medical management. These findings support the use of naltrexone and intensive medical management in primary care settings as a potential alternative to specialized treatment. Delivering the type of medical management provided in this study, however, requires substantial training and a collaborative care model. This requirement and other concerns (e.g., need for chronic treatment; acamprosate’s perplexing lack of efficacy, which was also reported in another recent study) require further investigation.

Kevin L. Kraemer, MD, MSc

Reference:

Anton RF, O’Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence. The COMBINE Study: a randomized controlled trial. JAMA. 2006;295(17):2003–2017.