What is antabuse?

History of Use

Disulfiram was discovered in the United States in 1937 by E. E. Williams when employees for the chemical plant Williams worked at were exposed to disulfiram and later experienced physical discomfort upon ingesting alcohol. One of the first medications specifically indicated for alcohol abuse, disulfiram was approved by the US Food and Drug Administration in 1951. Disulfiram was first used in high doses, up to 3,000 milligrams (mg), and was regularly used in the treatment of persons with alcohol dependence or abuse. These high dosages often led to undesired, adverse effects and, on rare occasions, deaths.

Dosing recommendations now are much more conservative. Patients should start with 500 mg as a single daily dose. After one to two weeks, depending on response, the dose may be decreased to a range of 125 to 250 mg daily. Therapy should continue until the patient and the patient’s caregiver decide that a full recovery has been achieved; this may take up to a few years in some patients. These dosing requirements represent the minimum drug concentration necessary to achieve the amount of physical discomfort targeted, should the patient ingest alcohol.

Initially used in persons with alcohol dependence, disulfiram also has shown potential benefit in persons addicted to cocaine. Multiple clinical trials on the use of disulfiram for the treatment of cocaine dependence and methamphetamine dependence are in various stages of completion. Disulfiram is estimated to be used by about two hundred thousand alcoholics in the United States. The number of persons treated with disulfiram is far fewer than the estimated seventeen million or more persons with alcohol dependence or abuse in the United States.

Effects and Potential Risks

Disulfiram inhibits aldehyde dehydrogenase (ALDH), the enzyme that converts acetaldehyde to acetate in the liver during the metabolism of alcohol. In the absence of disulfiram, acetaldehyde is quickly converted to acetate. Acetaldehyde levels are increased because of the inhibition of ALDH, which leads to the constellation of adverse effects. The adverse effects occur immediately and can include, at a mild level, headache, facial flushing, and sweating. Effects experienced in a moderate reaction can include nausea, tachycardia, hyperventilation, hypotension, and respiratory difficulties. In the most severe reactions, persons can experience serious cardiovascular decomposition, which could lead to death. The severity of the reaction depends on both the dose of disulfiram and the amount of alcohol ingested.

This medication should not be given to anyone without their knowledge and should not be given less than twelve hours after alcohol ingestion because of the risk of an unintended disulfiram-ethanol reaction. Even upon discontinuation of disulfiram treatment, the drug can remain in circulation for up to fourteen days, and alcohol must be avoided during this whole period.

Adherence is another hurdle to success with disulfiram. Studies have shown that supervised medication ingestion or other incentives to take the medication may result in higher rates of adherence. Side effects that occur even without ingestion of alcohol, although generally mild, include drowsiness, headache, and taste disturbances and can lead patients to stop taking the medication.

Disulfiram is available in tablet form and may be crushed and mixed with liquids. Disulfiram use can increase liver function tests into abnormal values and should be monitored before therapy initiation and again a few weeks after beginning therapy. Often, patients with alcohol dependence have underlying liver dysfunction.

Bibliography

Pani, P. P., et al. “Disulfiram for the Treatment of Cocaine Dependence.” Cochrane Database of Systematic Reviews 20.1 (2010): CD007024. Web. 8 Feb. 2012.

Soghoian, Samara, Sage W. Wiener, and Jose Eric Diaz-Alcala. “Toxicity, Disulfiram.” WebMD. Aug. 2008. Web. 9 Mar. 2011.

Suh, Jesse J., et al. “The Status of Disulfiram: A Half of a Century Later.” Journal of Clinical Psychopharmacology 26 (2006): 290–302. Print. .

Wright, Curtis, and Richard D. Moore. “Disulfiram Treatment of Alcoholism.” American Journal of Medicine 88 (1990): 647–55. Print.