After reading this article, you will be familiar with:
• Identifying the typical daily doses of FDA-approved medications for the treatment of alcohol dependence.
• Describing the significance of medication adherence on treatment outcomes in patients with alcohol dependence.
• Detailng strategies for recognizing, probing and improving medication nonadherence in patients who are prescribed a medication for a chronic illness like alcohol dependence.
• Describing novel options that might enhance medication adherence.

Alcoholism is a chronic and serious disorder with often devastating consequences. One out of three families in the United States is negatively impacted by a family member's excessive drinking and painful drinking-related problems.¹ Sadly, alcohol disorders are largely undertreated. The National Institute of Alcohol Abuse and Alcoholism (NIAAA) estimates that of the approximately 7.9 million people in the United States who suffer from alcohol dependence, only approximately 2.2 million people seek treatment.²

For decades, the standard in the United States for treating alcohol dependence, following detoxification, has been addiction-specialty counseling and regular attendance at mutual support groups like Alcoholics Anonymous. (Only a percentage of patients with alcohol dependence seek medical treatment for their disorder.³ This is highlighted by the fact that pharmacologic agents for the treatment of alcohol dependence have been available for over 10 years. However, historically, only a small fraction of patients are ever prescribed a pharmacologic agent—Ed.) Successful treatment recovery rates, while notable, still leave a large proportion of people who continue to drink heavily even in treatment or who rapidly relapse following treatment. Analysis of data from the NIAAA 2001-2002 U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) found that among alcohol-dependent patients who have received treatment, 54.5% relapsed soon after completing treatment. ² Initiating pharmacotherapy with counseling, in a number of cases, has been shown to be a valuable tool toward reducing relapse rates and increasing abstinence in alcohol-dependent patients. The NIAAA advises clinicians to consider initiating medications that have been approved by the U.S. Food and Drug Administration in patients who are still drinking or are abstinent but continue to experience slips or intense cravings for alcohol.⁴

In addition, however, it is recognized that the success of pharmacotherapy is largely dependent on an individual's adherence to taking the medication as prescribed. Daily pill-taking over an extended period of time can often be problematic, not just for patients with addictions, but for anyone suffering from a chronic disorder. Higher levels of medication nonadherence have been associated with patients suffering from psychiatric disorders, including addictive disorders.⁵ This article briefly describes the FDA-approved medications for the treatment of alcohol dependence and discusses strategies to address treatment challenges like medication nonadherence.

Initiating pharmacotherapy
In the last decade, as more knowledge has been discovered about the neurobiology of addiction and the effects of alcohol on the brain, clinical studies have been completed on initiating medications with counseling (types of counseling have ranged from medical management and advice to addiction-specialty therapies). These studies have been systematically conducted for the purpose of evaluating the advantage of pharmacotherapy in improving early and long-term outcomes. Essentially, medications are evaluated as to whether or not they provide an incremental advantage to counseling, or whether or not they can be paired with a relatively modest type of medical management counseling as an alternative to more intensive and specialized addiction therapy. To date, the FDA has approved four medications for the treatment of alcohol dependence; they are listed in the Table with other relevant information.

Disulfiram's (Antabuse) mechanism of action is different from the other subsequent medications that have been approved by the FDA for alcoholism. Disulfiram blocks aldehyde dehydrogenase, an enzyme needed to convert acetaldehyde to acetate for the body to fully metabolize alcohol.⁶ When someone taking disulfiram consumes alcohol, its enzyme-blocking action creates disagreeable physical symptoms, primarily nausea and vomiting. The usual daily dose of disulfiram prescribed today is 250 mg/day, but the unpleasant symptoms are dose dependent. That is, the aversive reaction escalates with a higher daily dose of disulfiram and/or with greater quantities of alcohol. Severe ethanol-disulfiram reactions, even death, have been reported, but were almost always associated with much higher daily doses (e.g., 1000 mg/day to 3000 mg/day).

While usually the unpleasant feelings will cause most people to stop drinking, disulfiram prescribers primarily believe that it is the psychological threat of discomfort that deters a disulfiramtreated patient from drinking any alcohol, which, in turn, removes the patient's chances of actually experiencing aversive symptoms.⁶ When patients are highly motivated or are supervised in their taking of disulfiram, it has been reported that drinking is avoided and thus aversive symptoms are not experienced. Treatment regimens including incentivedriven interventions or disulfiram supervision by physicians have shown beneficial treatment outcomes, such as decreases in drinking and increases in the rate of abstinence.⁵ However, in many primarily unsupervised situations, patients essentially have not accepted this medication, and, rather than discontinuing their alcohol intake, they stop taking disulfiram. Fuller and colleagues⁷ reported an astoundingly high nonadherence rate of 80% in a large multisite study of alcohol-dependent patients who were asked to take 250 mg/day of disulfiram or placebo. See Suh et al.⁶ for more information on disulfiram.