Advances in the use of naltrexone: an integration of preclinical and clinical findings.

Both preclinical and clinical studies are critical in the development of effective pharmacotherapeutic approaches for treating alcoholism. Nowhere has this been more evident than in the development of naltrexone for treating alcohol relapse. As studies continue on the use of naltrexone for modifying alcohol intake, promising avenues for continued work on maximizing the efficacy of naltrexone for treating alcohol abuse and alcoholism are emerging. Recent research suggests that naltrexone can influence key components of alcohol dependence, including loss of control over the decision to drink and the amount of alcohol consumed. Although not uniformly positive, the majority of clinical trials supports the hypothesis that naltrexone can reduce the urge to drink, increase the number of days abstinent, and minimize the risk of relapse to heavy drinking. Human laboratory and preclinical paradigms that have investigated how naltrexone alters patterns of drinking suggest that naltrexone treatment results in earlier cessation of drinking within a session. In addition, preclinical data suggest that the amount of alcohol consumed declines during subsequent sessions in the presence of naltrexone. Based on this analysis, future clinical trials should consider using analytic approaches that evaluate patterns of drinking (e.g., multiple event analysis) rather than single events (e.g., survival analysis). Furthermore, behavioral interventions and instructions can also be developed to take advantage of this effect. Additional preclinical and clinical work is warranted to identify dosing strategies that ensure adequate drug levels while reducing the possibility of developing tolerance to naltrexone. Finally, studies designed to identify the characteristics of drinking populations that are responsive to naltrexone and studies investigating the potential advantage of combining naltrexone with agents that alter a number of neurotransmitter systems are exciting new avenues of research. Ultimately, these lines for research promise to provide critical information that can be used to maximize the efficacy of naltrexone for treating alcoholism.