Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.
The Combined Pharmacotherapies and Behavioral Interventions (COMBINE) Study was designed to evaluate the efficacy of of medications, behavioral therapies, and their combination, for treating alcohol dependance. Naltrexone, behavioral therapy, and their combination were associated with better drinking outcomes. Acamprosate was not associated with improved outcomes. Meeting with a health care professional to receive placebo pills had a greater effect during treatment than behavioral therapy with no pills.
- N=1,383 recently alcohol-abstinent adults with DSM-IV diagnosis of primary alcohol dependence, randomized to one of nine groups.
- 4 groups received combined behavioral intervention (CBI) + medical management (MM) + medication:
- Acamprosate (n=151)
- Naltrexone (n=155)
- Acamprosate + Naltrexone (n=157)
- Placebo (n=156)
- 4 groups received medical management (MM) + medication (no CBI):
- Acamprosate (n=152)
- Naltrexone (n=154)
- Acamprosate + Naltrexone (n=148)
- Placebo (n=153)
- 1 group received CBI only (no pills) (n=157).
- Medical Management (MM) was performed by a licensed health care professional over 9 sessions, and was given to patients receiving placebo pill as well as active drug. Practitioners helped patients develop adherence plans and encouraged attending support groups in the community.
- Combined Behavioral Intervention (CBI) was performed by a licensed behavioral health specialist in up to twenty 50-minute sessions, integrating aspects of CBT, 12-step program, motivational interviewing, and support system involvement.
- Site: recruitment from 11 academic sites in the United States.
- Patients received 16 weeks of outpatient treatment, then were followed for up to one year after treatment.
- Primary outcomes: percent days abstinent from alcohol, and time to first heavy drinking day.
- Secondary outcome: good clinical outcome was a composite measure defined as abstinence or moderate drinking without problems (significant physical, social, or psychological consequences).
- Patients assessed 9 times during 16-week treatment, and at 26, 52, and 68 weeks after randomization.
- Drinking was substantially reduced in all groups.
- During treatment, 2-factor naltrexone X CBI interaction was significant (P=0.009).
- Naltrexone was associated with reduced risk of a heavy drinking day (Hazard Ratio: 0.72, 97.5% CI 0.53-0.98, P=0,02).
- Acamprosate was not associated with any significant effect on drinking compared with placebo, either by itself, or in combination with naltrexone, CBI, or both.
- Good clinical outcomes at the end of treatment (a composite measure) were seen in:
- 74% for naltrexone + MM + CBI
- 74% for naltrexone + MM
- 71% for placebo + MM + CBI
- 58% for placebo + MM
- For the 8 groups receiving pills, average percent days abstinent ranged from 73.8%-80.5%. Placebo pills plus medication management were associated with significant improvement in drinking (P<0.001) compared with CBI alone. Percent days abstinent:
- 66.6% for CBI alone
- 73.8% for placebo + MM
- 79.8% for placebo + MM + CBI
- Between-group effects were no longer significant one year after treatment.
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. doi:10.1001/jama.295.17.2003.