Pharmacotherapy for Alcoholism and Some Related Psychiatric and Addictive Disorders: Scientific Basis and Clinical Findings

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration has approved naltrexone and a derivative depot formulation (Vivitrol®) for the treatment of alcohol dependence, but their therapeutic effect sizes are small. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. The Food and Drug Administration also has approved acamprosate for the treatment of alcohol dependence based on the results of these European trials. Notably, however, studies in the United States have not found efficacy for acamprosate. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study, but this was not confirmed in a multi-site study in the United States. Another Food and Drug Administration–approved medication for the treatment of alcohol dependence, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Promising medications continue to be developed for the treatment of alcohol dependence. Of these, topiramate has demonstrated a medium therapeutic effect size in large clinical trials. Another promising medication, baclofen, has shown efficacy in small trials, and might be particularly useful to treat alcohol-dependent individuals with liver cirrhosis. Serotonergic agents such as selective serotonin reuptake inhibitors appear to be efficacious only among certain subtypes of alcoholic. Exciting new research has shown the utility of the serotonin-3 receptor antagonist, ondansetron, as a pharmacogenetic treatment for alcohol dependence. There has been renewed interest in developing gamma-hydroxybutyric acid for treating alcoholism; however, novel dosage formulations will be needed to reduce its potential for addiction. Many comorbid psychiatric and addictive disorders have been associated commonly with alcohol dependence. Nevertheless, only those areas in which systematic pharmacotherapy studies have been done to identify efficacious medicines to treat these conditions have been selected for a brief discussion. Among psychiatric disorders, alcohol dependence is most commonly associated with affective disorders—particularly bipolar disorder and depression—and anxiety-related disorders, including social phobia. Valproic acid and topiramate are being investigated currently as promising treatments for alcohol dependence in those with bipolar disorder. Despite the lack of approved medicines for these indications, experimental treatment with a selective serotonin reuptake inhibitor both with and without naltrexone might be useful for treating comorbid alcohol dependence and depression. Ondansetron and the selective serotonin reuptake inhibitor paroxetine have both shown utility for the treatment of alcohol-dependent individuals with social phobia. Another selective serotonin reuptake inhibitor, sertraline, may have utility in treating individuals with comorbid post-traumatic stress disorder and alcohol dependence. There are no specific treatments for alcohol dependence complicated by general anxiety disorder. Alcohol dependence among smokers is, perhaps, the most studied in pharmacotherapy trials. Of the medications studied, the most promising appear to be topiramate and varenicline.