The present application seeks two years of funding to complete COMBINE and its ancillary cost-effectiveness and genetic predictors of treatment response studies. The COMBINE study was initiated in 1997 to answer questions about the benefits of combining behavioral and pharmacological interventions. Two medications, naltrexone and acamprosate, have shown promise in reducing relapse to heavy drinking and improving abstinence in a number of U.S. and European clinical trials. The two behavioral treatments, Medical Management (MM) and Combined Behavioral Intervention (CBI), have potential to be valuable adjuncts to pharmacotherapy. MM appears to be cost-effective and suitable for delivery in primary care or managed care settings by non-specialists. The primary hypothesis is that combining the two medications (naltrexone and acamprosate) with a moderate intensity behavioral treatment (CBI) will yield better outcomes than less intensive approaches (e.g., placebo and MM; acamprosate or naltrexone and MM) for alcohol dependent patients. A total of 1375 subjects from 11 clinical sites comprise the targeted sample. Individuals meeting study criteria have been randomly assigned to one of nine pharmacological (naltrexone and acamprosate) and behavioral treatment (MM and CBI) combinations to form a complete 2X2X2 factorial design. A ninth cell was later included to test the efficacy of CBI without """"""""pills"""""""". Much has been accomplished since COMBINE's initiation. Over 70% of the intended sample has been randomized to the study treatments reflecting gender, ethnic, geographic, and clinical diversity. Drinking assessment interviews have been completed for 84% clients at the 16-week follow-up. Two major pilot studies were successfully completed and the findings have been disseminated at conferences and in publications. The requested two-year extension will allow for the recruitment, treatment, and follow-up of the remaining participants, and allow sufficient time for data analysis and manuscript preparation. Results from the COMBINE study are expected to have a major impact on the alcohol treatment delivery system. A common protocol across each of the study sites is submitted. This reflects the cooperative process that has guided the study's efforts across the first five years of operation. However, each study site has provided site-specific information on the budget, budget justifications, listing of key personnel, consultant/consortium agreements, and human subjects .

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
Application #
Study Section
Special Emphasis Panel (ZAA1-BB (10))
Program Officer
Litten, Raye Z
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Biostatistics & Other Math Sci
Schools of Public Health
Chapel Hill
United States
Zip Code
Doyle, Suzanne R; Donovan, Dennis M; Simpson, Tracy L (2011) Validation of a nine-dimensional measure of drinking motives for use in clinical applications: the desired effects of drinking scale. Addict Behav 36:1052-60
Oroszi, Gabor; Anton, Raymond F; O'Malley, Stephanie et al. (2009) OPRM1 Asn40Asp predicts response to naltrexone treatment: a haplotype-based approach. Alcohol Clin Exp Res 33:383-93
Doyle, Suzanne R; Donovan, Dennis M (2009) A validation study of the alcohol dependence scale. J Stud Alcohol Drugs 70:689-99
Ray, Lara A; Oslin, David W (2009) Naltrexone for the treatment of alcohol dependence among African Americans: results from the COMBINE Study. Drug Alcohol Depend 105:256-8
DiClemente, Carlo C; Doyle, Suzanne R; Donovan, Dennis (2009) Predicting treatment seekers' readiness to change their drinking behavior in the COMBINE Study. Alcohol Clin Exp Res 33:879-92
Anton, Raymond F; Oroszi, Gabor; O'Malley, Stephanie et al. (2008) An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry 65:135-44
Ernst, Denise B; Pettinati, Helen M; Weiss, Roger D et al. (2008) An intervention for treating alcohol dependence: relating elements of Medical Management to patient outcomes with implications for primary care. Ann Fam Med 6:435-40
Weiss, Roger D; O'malley, Stephanie S; Hosking, James D et al. (2008) Do patients with alcohol dependence respond to placebo? Results from the COMBINE Study. J Stud Alcohol Drugs 69:878-84
Donovan, Dennis M; Anton, Raymond F; Miller, William R et al. (2008) Combined pharmacotherapies and behavioral interventions for alcohol dependence (The COMBINE Study): examination of posttreatment drinking outcomes. J Stud Alcohol Drugs 69:5-13
Doyle, Suzanne R; Donovan, Dennis M; Kivlahan, Daniel R (2007) The factor structure of the Alcohol Use Disorders Identification Test (AUDIT). J Stud Alcohol Drugs 68:474-9

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