Combined Pharmacotherapies for the Management of Alcoholism: Rationale and Evidence to Date

Mary R. Lee, Lorenzo Leggio

Pharmacotherapies for alcohol use disorders (AUDs) have limited efficacy. One approach to improving treatment outcomes for AUDs is to combine pharmacotherapies that have shown some efficacy as individual agents. The rationale for combining medications rests on the following principles: a combination of medications can target more than one neurotransmitter system that is dysfunctional in AUDs, can target different drinking behaviors (i.e., positive and negative reinforcement), can treat co-morbid psychiatric and medical disorders, and can minimize side effects, improving adherence to treatment by using lower doses of each drug in combination. Combined pharmacotherapy strategies may produce additive or even synergistic effects to decrease alcohol craving and consumption. Here, we reviewed the literature investigating the effect on alcohol-related outcomes of combinations of medications that have shown efficacy as single agents to reduce drinking in animal studies and clinical trials. We focused on 17 clinical studies investigating the combination of medications in AUDs, 11 of which were randomized, double-blind, and placebo-controlled. Ten of the 11 studies showed the combination to be superior to placebo, but only three showed an advantage of the combination compared with the single agent. Overall, these studies used diverse methodologies, assessments of severity, outcome measures, and adjunctive psychosocial treatments. Limitations of the current published studies and possible future directions for new combinations are discussed.