Combining treatments for alcoholism: why and how?

Treatment of alcohol disorders through the use of combinations of pharmacological and behavioral modalities may more effectively address the multicomponent nature of the disorder than single-modality approaches. Interdisciplinary models of the biological, psychological and social components of alcohol disorders are emerging rapidly from basic research, and treatment researchers have begun to test various strategies to combine medications and behavioral treatments. In addition to behavioral and pharmacological combinations, effective treatment pairs can be composed of two medications whose mechanisms of action are believed to be compatible and potentially additive, or even synergistic. Combining Medications and Behavioral Interventions (COMBINE) is a large multisite clinical trial sponsored by the National Institute on Alcohol Abuse and Alcoholism. Its goal is to determine if improvements in treatment outcome for alcohol dependence can be achieved by combining pharmacotherapy and behavioral interventions. Under evaluation is the efficacy of two promising medications (naltrexone and acamprosate), both singly and together, when used in conjunction with two behavioral treatments of differing intensities. This supplement describes in detail the methods and rationale for the approach taken in COMBINE. This first article in the supplement has three objectives: (1) to review strategies for conducting combination treatment studies as illustrated with selected examples from the literature, (2) to summarize the main design features of COMBINE as background for the articles in this supplement and (3) to comment on future directions for combination treatment research as the field moves beyond COMBINE.