Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

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 potential appears to be the most widely established. In the USA, naltrexone was approved by the Food and Drug Administration in 1995 for the treatment of alcoholism; however, the results of some studies have been less encouraging. Naltrexone's reliance on high compliance rates for efficacy may, eventually, limit its potential in clinical settings offering generic treatment for alcoholism. The relative paucity of dose-response studies on naltrexone's effects in treating alcoholics is an important gap in the literature. Recent data from a large clinical trial suggests that ondansetron, a serotonin3 antagonist, offers new hope for the treatment of early onset alcoholics; a type of alcoholism most difficult to manage with psychosocial measures alone. Different subtypes of alcoholic may, therefore, have varying treatment responses to serotonergic agents. Matching subtypes of alcoholic to effective treatment medications based upon their different biologies remains an important therapeutic goal. Combinations of effective pharmacological agents need exploration as they may prove to be synergistic, and could shepherd in a new era of treatments aimed at multiple neurotransmitter targets associated with the alcoholism disease. The coming decade promises more powerful tools for characterizing drug effects on alcohol drinking, thereby closing the gap between animal models of addiction and the human condition.