Neuropharmacological treatments for alcoholism: scientific basis and clinical findings

Preclinical studies have exploded our knowledge about the behavioral and bi ological underpinnings of alcoholism. These studies suggest that certain ne urotransmitters, particularly those interacting with the opioid, N-methyl-D -aspartate, and monoamine systems, may play a critical role in the expressi on of alcohol-drinking and other behaviors associated with its abuse liabil ity. Built upon this foundation, important advances have been made in the d evelopment of therapeutic medications for the treatment of alcoholism. Of t he medications reviewed, acamprosate's potential appears to be the most wid ely established. In the USA, naltrexone was approved by the Food and Drug A dministration 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 clini cal settings offering generic treatment for alcoholism. The relative paucit y of dose-response studies on naltrexone's effects in treating alcoholics i s an important gap in the literature. Recent data from a large clinical tri al suggests that ondansetron, a serotonin, antagonist, offers new hope for the treatment of early onset alcoholics; a type of alcoholism most difficul t to manage with psychosocial measures alone. Different subtypes of alcohol ic may, therefore, have varying treatment responses to serotonergic agents. Matching subtypes of alcoholic to effective treatment medications based up on their different biologies remains an important therapeutic goal. Combina tions of effective pharmacological agents need exploration as they may prov e 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 effe cts on alcohol drinking, thereby closing the gap be tween animal models of addiction and the human condition.