[Show abstract][Hide abstract] ABSTRACT: In recent years, the field of medication development aimed at treating alcoholism and drug dependence has benefited greatly from neuropsychopharmacologic research pertaining to glutamate antagonists. Acamprosate is the medication studied most extensively as pharmacotherapy for alcohol dependence. Although European studies have found acamprosate to be efficacious, studies in the United States have not. This discrepancy could be due to differences in the clinical picture of study participants. Important predictors of response to acamprosate treatment include prominent signs of physiologic dependence, negative family history, anxiety, later age of onset, and female gender. Other N-methyl-D-aspartate antagonists, including memantine, need to be studied further as potential pharmacotherapies for alcoholism. The novel compound topiramate, which is an antagonist at α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid and kainate glutamate receptors, has demonstrated efficacy in the treatment of alcoholism in an undifferentiated population. Further studies to establish this finding are ongoing. For drug addiction other than alcoholism, topiramate is the one glutamate antagonist that has shown the most promise in clinical populations to date, particularly for cocaine- and nicotine-dependent individuals. Results from these studies, however, are preliminary and need to be confirmed by additional research, which is currently under way.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Alcoholism and nicotine dependence share many neurobiological underpinnings; the presence of one drug can cause a person to crave the other. Depressive illness can complicate comorbid alcohol and nicotine dependence by exacerbating the negative affect encountered during attempts to abstain from one or both drugs. Given the morbidity and mortality associated with cigarette smoking, it is imperative to identify treatments to promote smoking cessation and address comorbid psychiatric conditions contemporaneously. Pharmacotherapeutic options demonstrating varying degrees of efficacy and promise in preclinical and clinical studies include nicotine replacement therapy (NRT), selective serotonin reuptake inhibitors (SSRIs), bupropion, varenicline, tricyclic antidepressants, and bupropion plus NRT. Topiramate has shown potential for promoting smoking cessation in alcoholics, although its safety in depressed patients has not been fully explored. The efficacy of medications for treating nicotine dependence is generally enhanced by the inclusion of behavioral interventions such as cognitive behavioral therapy. When group cohesion and social support are stressed, success rates increase among depressed smokers undergoing smoking cessation treatment. Additional treatment strategies targeting dually dependent individuals with comorbid psychiatric disorders, including special populations such as women and adolescents, await further investigation.
Alcohol research & health: the journal of the National Institute on Alcohol Abuse and Alcoholism 02/2006; 29(3):213-20. · 0.58 Impact Factor
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