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

Abstract

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol use disorder. The US Food and Drug Administration (FDA) has approved naltrexone and a derivative depot formulation (Vivitrol) for the treatment of alcohol use disorder, but their therapeutic effect sizes are small. Nalmefene, like naltrexone, also an opioid antagonist, has been approved in Europe for the treatment of alcohol use disorder; however, the effect size appears small. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. The FDA 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 individuals with alcohol use disorder 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 multisite study in the United States. Another FDA-approved medication for the treatment of alcohol use disorder, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram appears to be 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 use disorder. Of these, topiramate has demonstrated a medium therapeutic effect size in large clinical trials. Another promising medication, gabapentin, has shown efficacy in human laboratory and single-site large clinical trial and may be a suitable medication for those with sleep problems. The results of a multicenter clinical trial are, however, awaited. Baclofen, licensed only in France for the treatment of alcohol use disorder, has shown efficacy in relatively small European trials, and observational studies, and might be useful to treat individuals with alcohol use disorder and liver cirrhosis. Clinical studies in the United States have, however, not generally confirmed baclofen’s efficacy in treating alcohol use disorder. Serotonergic agents such as selective serotonin reuptake inhibitors appear to be efficacious only among certain subtypes of individuals with alcohol use disorder. Exciting new research has shown the utility of the serotonin-3 receptor antagonist, ondansetron, as a pharmacogenetic treatment for alcohol use disorder. There has been renewed interest in developing γ-hydroxybutyrate for treating alcohol use disorder; however, the evidence for efficacy is not compelling, and 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 use disorder 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 use disorder 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 use disorder and depression. Ondansetron and the selective serotonin reuptake inhibitor paroxetine have both shown utility for the treatment of individuals with alcohol use disorder and social phobia. Another selective serotonin reuptake inhibitor, sertraline, may have utility in treating individuals with comorbid posttraumatic 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 cosubstance use pharmacotherapy trials. Of the medications studied, the most promising appear to be topiramate and varenicline.