Pharmacological Adjuncts in the Treatment of Alcohol Dependence. Lecture Summary

Acamprosate
Preclinical studies have exploded our knowledge about the behavioral and biological underpinnings of alcoholism. These studies suggest that certain neurotransmitters, particularly those interacting with the opioid, N-Methyl-D-Aspartate, and monoamine systems may play a critical role in the expression of alcohol-drinking and other behaviors associated with its abuse liability. Built upon this foundation, important advances have been made in the development of therapeutic medications for the treatment of alcoholism. Of the medications reviewed, acamprosate's efficacy is the most widely established.

Naltrexone
In the U.S., naltrexone has been licensed by the Food and Drug Administration for the treatment of alcoholism; however, high compliance rates may be critical for efficacy. Elucidation of naltrexone's dose-response characteristics, and demonstration of its utility in large-scale clinical trials are still needed.

Combination Strategies
Combinative medication strategies offer the potential for synergism at improving drinking outcomes by targeting multiple neurotransmitters. Presently, NIAAA is testing the relative efficacy of independent vs. concomitant use of naltrexone and acamprosate for alcoholism treatment; however, other logical combinations exist.

Ondansetron
Recent data from a large clinical trial suggests that ondansetron, a serotonin3 antagonist, offers new hope for the treatment of early onset alcoholics; just the type of alcoholic most difficult to manage with psychosocial measures alone. Different subtypes of alcoholic may, therefore, have varying treatment responses to serotonergic agents. These findings emphasize the need for more mechanism-based clinical trials in the alcoholism field, and may shepherd in a new era in which alcoholics are matched to treatment based upon their biological or genetic differences. Future development and integration of pharmacologic, neuroimaging, and molecular genetic tools for characterizing drug effects on alcohol drinking may help to close the gap between our understanding of animal models of addiction and the human condition.