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Pharmacological Treatments for Heavy Drinking

by henry r. kranzler, m.d.

Drinking patterns vary considerably among individuals. However, medical and psychosocial problems increase as average drinking exceeds low levels and the frequency of intoxication increases. Although individuals with an alcohol use disorder (AUD) are often the focus of treatment efforts, heavy drinkers (who may not meet criteria for an AUD) are more numerous and a growing public health concern. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has identified low-risk drinking as weekly consumption of less than 8 drinks for women and 15 drinks for men, with no heavy drinking (i.e., for women, no more than 3 drinks in a day and, for men, no more than 4 drinks in a day). The clinically important adverse effects of heavy drinking suggest that interventions, including pharmacotherapy, are warranted for individuals who regularly exceed the NIAAA guidelines.

The major pharmacological approaches to treat heavy drinking are deterrent medications (e.g., disulfiram), which produce adverse effects when alcohol is consumed, and medications that modify the activity of one or more of the neurotransmitter systems mediating alcohol reinforcement (e.g., opioid antagonists). Disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) to treat alcoholism, which occurred prior to the implementation of the rigorous requirements for efficacy that now exist. When combined with alcohol, disulfiram produces a characteristic set of unpleasant signs and symptoms, which are thought to deter drinking. However, in the largest controlled study of disulfiram, its beneficial effects were modest, though it may be more useful among alcoholics with whom special efforts are made to ensure compliance.

The opioid antagonists naltrexone and nalmefene have been approved to treat alcohol dependence in the United States and the European Union, respectively. In 1994, the FDA approved oral naltrexone, based on the results of two single-site studies, which showed it to be efficacious in the prevention of relapse to heavy drinking. The most recent meta-analysis of naltrexone showed that it reduced the risk of any heavy drinking by about 17% relative to placebo and significantly reduced the number of heavy drinking days. Two alternatives to daily naltrexone treatment include a long-acting injectable formulation of naltrexone, which the FDA approved in 2006, and the “targeted” use of the oral medication to high-risk drinking situations. This as-needed approach was the basis for the recent approval of nalmefene by the European Medicines Agency to reduce heavy drinking in alcohol-dependent individuals.

Acamprosate is an amino acid derivative, the safety and efficacy of which have been well demonstrated in Europe. In 2004, the FDA approved acamprosate for clinical use in the United States. A subsequent meta-analysis showed that acamprosate significantly reduced the risk of any drinking and increased the cumulative duration of abstinence. However, placebo-controlled, multicenter trials in the United States, Europe and Australia failed to detect beneficial effects of acamprosate in the treatment of alcohol dependence.

The anticonvulsant topiramate, although not approved to treat alcohol dependence, shows considerable promise in single-site and multi-center trials to reduce heavy drinking. The active medication resulted in significant reductions in drinks/day, drinks/drinking day, drinking days, and heavy drinking days. Although apparently more efficacious than other treatments for heavy drinking, topiramate treatment is associated with a variety of adverse events, which can limit its clinical utility.

In summary, a growing number of medications have been approved to treat alcohol dependence. It appears that these medications also can be used to reduce heavy drinking in individuals whose goal is not to stop drinking completely. This creates a new opportunity for primary care practitioners and psychiatrists to intervene pharmacologically with heavy drinkers. Further research that considers how best to assist heavy drinkers in reducing their drinking is needed to diminish the substantial medical and psychosocial risks associated with this behavior.

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Henry R. Kranzler, M.D., is a professor of psychiatry at the Perelman School of Medicine of the University of Pennsylvania. He is the co-editor of Clinical Manual of Addiction Psychopharmacology, published by American Psychiatric Publishing. APA members may purchase the book at a discount here.

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