Pharmacotherapy of alcoholism: gaps in knowledge and opportunities for research.

During the past decade, renewed interest in medications to prevent relapse in alcoholics has yielded a number of promising candidates. Although two of these medications, naltrexone and acamprosate, are currently in clinical use in a number of countries, overall, their effectiveness appears to be limited. Disulfiram, the deterrent medication that was approved 50 years ago for the treatment of alcoholism, has not consistently been shown to be efficacious. However, since inadequate dosing and other modifiable factors may limit its deterrent effects, the identification of a more potent metabolite of disulfiram appears to warrant further evaluation. Studies of serotonergic agonists for treatment of alcoholism have also yielded inconsistent results. There is evidence, however, that subgroups of alcoholics may respond well to such medications, suggesting that treatment matching may enhance their efficacy. In addition, nalmefene, a compound with effects similar to naltrexone, as well as a sustained release formulation of naltrexone, may enhance the beneficial effects of opioid antagonist therapy. Despite these developments, much remains to be learned about the pharmacotherapy of alcoholism. The ongoing development and evaluation of novel medications should be given a high priority. However, such basic issues as the optimal dosing strategy and duration of treatment for existing therapies are not known. Similarly, combination therapy, involving either multiple medications or the combination of medication with specific psychotherapies, has not been well studied. The utility of specific pharmacotherapies in women, different ethnic/racial groups, adolescent and geriatric patients, and individuals with co-morbid alcohol and drug use disorders (including nicotine dependence) is also largely unknown, as is the appropriateness of medication therapy for treatment of early problem drinkers. The ultimate aim of these efforts is the development of algorithms for the pharmacological treatment of heavy drinking, which incorporate the characteristics of the patient and of pharmacological and psychosocial treatments with demonstrated efficacy. Although a general framework for such an effort currently exists, much detail is needed before it will be of widespread clinical value.