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Efficacy of Drug Therapies for Alcohol Dependence
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Am Fam Physician. 1999 Oct 15;60(6):1827-1828.
Forty to 70 percent of patients who undergo treatment of alcohol dependence relapse within one year. Interest in drug therapy to help persons abstain from drinking has heightened as our understanding of addictive disorders has increased. In a review article, Swift discusses the use of drug therapy for alcohol dependence.
In the United States, only two drugs—disulfiram and naltrexone—are approved for the treatment of alcohol dependence. Although disulfiram is reported to be effective as an aversive drug, placebo-controlled clinical trials have been inconclusive. One study of 605 alcohol-dependent men found no difference in the rates of abstinence and time to a first drink at one year in the men who received 1 mg of disulfiram, 250 mg of disulfiram or a placebo. Despite the lack of proven efficacy, some patients and physicians believe the drug serves as a psychologic deterrent. It is prescribed in a dosage ranging from 125 to 1,000 mg daily, but the usual dosage is 250 mg daily.
Disulfiram inhibits the metabolism of anticoagulant drugs, phenytoin and isoniazid. This drug should be used cautiously in patients with liver disease and is contraindicated during pregnancy and inpatients with ischemic heart disease. Disulfiram can cause hepatitis; monitoring of liver function studies is essential.
The second drug approved for use in the treatment of alcohol dependence is the opioid antagonist naltrexone. Naltrexone is believed to reduce consumption of alcohol and increase abstinence by reducing the craving for alcohol. A 12-week, placebo-controlled clinical trial of naltrexone in a dosage of 50 mg daily revealed that patients who received naltrexone had significantly fewer drinking days than those who received the placebo. Compared with the placebo group, fewer patients in the naltrexone group resumed heavy drinking. However, other studies have not demonstrated efficacy. Naltrexone did not reduce drinking in a study of 108 patients who received the placebo or naltrexone in a dosage of 50 or 100 mg daily. No differences were observed in a study of 175 patients with alcoholism. Similarly, a study of 64 patients with combined alcohol and cocaine dependence showed no more benefit with naltrexone than with the placebo. The author notes that compliance may have been an issue in the negative studies.
The author states that the rate of relapse is highest within 90 days of abstinence, and it is during this time that naltrexone may be beneficial. Daily dosages may range from 25 to 100 mg. Side effects include nausea, headache, anxiety and sedation. Naltrexone can be hepatotoxic at higher dosages and should be used with caution in patients with chronic liver disease.
Several selective serotonin reuptake inhibitors (SSRIs), including fluoxetine and sertraline, have been found to decrease alcohol intake by 15 to 20 percent in heavy drinkers without a history of depression. However, in other trials of SSRIs in patients with alcohol dependence these agents were found to be no more effective than a placebo. An exception is patients with alcohol dependence and major depression, in whom fluoxetine improved depression and was associated with a 50 percent decrease in the amount of alcohol consumed during a 12-week, placebo-controlled trial of 51 patients.
The author concludes that naltrexone and the as-yet unlabeled drug acamprosate show the strongest evidence of efficacy. However, the optimal dosage and duration of therapy remain to be determined. His enthusiasm for disulfiram and calcium carbimide (an agent available in Canada) is minimal because of the lack of proven efficacy. The author also emphasizes that any drug therapy should be combined with psychotherapy or group therapy to help address the social and psychologic aspects of alcohol dependence. He states that patients with psychiatric disorders such as depression and anxiety should be treated with drugs that are effective for the psychiatric condition.
Swift RM. Drug therapy for alcohol dependence. N Engl J Med. May 13, 1999;340:1482–90.
Copyright © 1999 by the American Academy of Family Physicians.
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