Novel Pharmacotherapies for Alcohol Dependence

Novel Pharmacotherapies for Alcohol Dependence

Rosenthal Richard N

US Psychiatry 2007;1:24-8

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Alcohol dependence is a highly prevalent disorder; however, despite the availability of evidence-based medical and psychosocial treatments it is infrequently diagnosed and generally undertreated. More than 8 million people over 18 years of age have alcohol dependence in any year, yet only 8% receive treatment in a specialty setting and fewer than 10% receive alcohol-specific pharmacotherapy.1Psychosocial treatments affect some components of alcohol dependence,2 while pharmacotherapy affects other aspects.3

For example, cognitive and behavioral skills for changing drinking behavior are facilitated by cognitive behavioral therapy (CBT), and readiness to change drinking behavior is improved by motivational interviewing.2 In contrast, specific neurotransmitters involved in the rewarding effects of alcohol or dysphoric states related to alcohol withdrawal or abstinence are the target of newer medications for alcohol dependence.4 These medications promote abstinence and reduce relapse to heavy drinking when a slip occurs. Adherence to medications is improved by integrating psychotherapy with the pharmacological treatment of alcohol-dependent patients.5,6 Because non-adherence to medications reduces their efficacy, psychosocial treatments that enhance medication adherence and treatment retention lead to better outcomes.7,8Psychosocial treatments should at least incorporate motivational enhancement, including patient feedback, emotional support, and medication monitoring.
Three medications are approved by the US Food and Drug Administration (FDA) for the treatment of alcohol dependence: disulfiram, oral and injectable naltrexone, and acamprosate. This paper will present these currently approved medications and also describe a few of the classes of medications that are being investigated for the treatment of alcohol dependence.

Medications for Alcohol Dependence Approved by the US Food and Drug Administration
Disulfiram
Disulfiram is FDA-approved as an aversive therapy for treating alcohol dependence. Disulfiram inhibits aldehyde dehydrogenase and blocks the oxidation of beverage alcohol, leading to a build-up of acetaldehyde; this produces aversive symptoms such as tachycardia, hypotension, diaphoresis, flushing, dyspnea, nausea, and vomiting. Patients taking disulfiram know what the aversive reaction will be and so are motivated to avoid alcohol ingestion.9 The typical oral dose of disulfiram is 250mg daily, with a maximum of 500mg daily. To avoid a reaction, it is not administered until the blood alcohol concentration is zero or until the patient has abstained from alcohol for 12 hours or more. Disulfiram is often used to treat patients who have previously failed one or more trials of psychosocial treatment7 and who are motivated to achieve complete abstinence.10In order to avoid experiencing a disulfiram–alcohol reaction, patients must avoid exposure to alcohol in any form, including mouthwashes, colognes, foods, etc. In addition, its use is contraindicated in ischemic heart disease and pregnancy. Serious adverse events associated with disulfiram use are cholestatic and fulminant hepatitis, hepatotoxicity, optic neuritis, peripheral neuritis, polyneuritis, and—with high doses—psychosis.11 Because disulfiram inhibits the induction of hepatic enzymes, it may impede the metabolism of concomitant drugs.

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