• Article

Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients

CONTEXT: The COMBINE (Combined Pharmacotherapies and Behavioral Intervention) clinical trial recently evaluated the efficacy of medications, behavioral therapies, and their combinations for the outpatient treatment of alcohol dependence. The costs and cost-effectiveness of these combinations are unknown and of interest to clinicians and policy makers.

OBJECTIVE: To evaluate the costs and cost-effectiveness of the COMBINE Study interventions after 16 weeks of treatment.

DESIGN: A prospective cost and cost-effectiveness study of a randomized controlled clinical trial.

SETTING: Eleven US clinical sites.

PARTICIPANTS: One thousand three hundred eighty-three patients having a diagnosis of primary alcohol dependence.

INTERVENTIONS: The study included 9 treatment groups; 4 groups received medical management for 16 weeks with naltrexone, 100 mg/d, acamprosate, 3 g/d, or both, and/or placebo; 4 groups received the same therapy as mentioned earlier with combined behavioral intervention; and 1 group received combined behavioral intervention only.

MAIN OUTCOMES MEASURES: Incremental cost per percentage point increase in percentage of days abstinent, incremental cost per patient of avoiding heavy drinking, and incremental cost per patient of achieving a good clinical outcome.

RESULTS: On the basis of the mean values of cost and effectiveness, 3 interventions are cost-effective options relative to the other interventions for all 3 outcomes: medical management (MM) with placebo ($409 per patient), MM plus naltrexone therapy ($671 per patient), and MM plus combined naltrexone and acamprosate therapy ($1003 per patient).

CONCLUSIONS: To our knowledge, this is only the second prospective cost-effectiveness study with a randomized controlled clinical trial design that has been performed for the treatment of alcohol dependence. Focusing only on effectiveness, MM-naltrexone-acamprosate therapy is not significantly better than MM-naltrexone therapy. However, considering cost and cost-effectiveness, MM-naltrexone-acamprosate therapy may be a better choice, depending on whether the cost of the incremental increase in effectiveness is justified by the decision maker.


Zarkin, G. A., Bray, J. W., Aldridge, A., Mitra, D., Mills, M. J., Couper, D. J., ... COMBINE Cost-Effectiveness Research Group (2008). Cost and cost-effectiveness of the COMBINE study in alcohol-dependent patients. Archives of General Psychiatry, 65(10), 1214-1221. https://doi.org/10.1001/archpsyc.65.10.1214