To study the effects of pharmacotherapy with behavioral intervention for alcohol dependence, researchers randomized 1,383 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 percent at 16 weeks and 82 percent a year later.

• Drinking outcomes improved substantially in all groups. For example, the range of mean percent days abstinent across groups was 23 to 30 percent at baseline, 67 to 81 percent at 16 weeks, and 59 to 69 percent 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 percent versus 75 percent) 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 percent versus 75 percent). However, CBI alone (without MM or pills) was less effective than placebo/MM (67 percent versus 74 percent).
• Acamprosate did not significantly affect drinking outcomes.
• One year after treatment, drinking outcomes did not significantly differ among groups.

Comments by Kevin L. Kraemer, MD, MSc:

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. 

*CBI was offered by a specialist and included elements of cognitive behavioral therapy, motivational interviewing, and 12-step facilitation in up to 20 50-minute sessions.

**MM included 9 counseling and education sessions (45-minute initial session and approximately 20-minute follow-up sessions) that were provided by a generalist healthcare professional and focused on medication side effects, adherence, and alcohol abstinence.

***Defined as up to 5 standard drinks per day for men, up to 4 for women

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.