Use of a "psychotherapy with no pills" treatment condition as part of a combined pharmacotherapy-psychotherapy research study of alcohol dependence.

Objective: The purpose of this article is to review issues related to the use of placebo medication in a study examining combined pharmacotherapy and psychotherapy for alcohol dependence.

Method: Little is known about the strength of the placebo effect in alcohol-dependent patients. One way to study this is to compare placebo to no pharmacological treatment. The multisite National Institute on Alcohol Abuse and Alcoholism COMBINE Study is examining optimal combinations of two medications (acamprosate and naltrexone) and two behavioral treatments (a moderate-intensity treatment called Combined Behavioral Intervention [CBI] and a low-intensity treatment called Medical Management [MM]) for alcohol-dependent patients. The study initially included a 2 x 2 x 2 eight-cell design. This article relates our experience adding a ninth treatment condition (Cell 9), consisting of CBI alone, with no pills or MM. By comparing patients receiving CBI alone to patients receiving two placebos, MM and CBI, we can examine the strength of the placebo effect for these two medications in alcohol-dependent patients. Moreover, we can study CBI in the context in which it is frequently delivered clinically, that is, in the absence of pharmacotherapy and certainly in the absence of placebo medication.

Results: This article explains the background and rationale behind the decision to include Cell 9 in COMBINE. Recruitment challenges faced as a result of adding this condition are reviewed, as is the experience implementing this condition in a pilot feasibility study.

Conclusions: The use of a "psychotherapy with no pills" treatment condition as part of a combined pharmacotherapy-psychotherapy study of alcohol dependence is feasible and can help enrich the results of this research.