Antabuse
Antabuse, also known as disulfiram, is a medication used primarily to treat alcohol use disorder (AUD) by acting as an alcohol-aversive agent. Classified as an aldehyde dehydrogenase (ALDH) inhibitor, Antabuse causes unpleasant reactions when alcohol is consumed, including flushing, sweating, and nausea. These symptoms are triggered by the accumulation of acetaldehyde in the body, as the drug inhibits the enzyme responsible for its breakdown. Originally discovered in 1937 and FDA-approved in 1951, its initial high dosing led to severe side effects, but modern recommendations suggest starting doses of 500 mg that may be adjusted based on individual response.
While primarily indicated for alcohol dependence, research has explored its effects on other substance use disorders, such as cocaine and methamphetamine addiction, although it is not FDA-approved for these uses. Antabuse is estimated to be used by about 200,000 individuals in the U.S., a number significantly lower than those with alcohol dependence. Adherence to treatment can be challenging, as the medication must be taken with a clear understanding of its effects and the necessity to avoid alcohol for an extended period, even after discontinuation. Monitoring for liver function abnormalities is also recommended, especially since many individuals with AUD may have underlying liver issues.
Subject Terms
Antabuse
- ALSO KNOWN AS: Disulfiram
DEFINITION: Antabuse (disulfiram) is classified as an aldehyde dehydrogenase (ALDH) inhibitor and is considered an alcohol-aversive drug. Persons taking disulfiram while also ingesting alcohol will experience a disulfiram-ethanol reaction. This reaction involves many symptoms, including flushing, sweating, and nausea. Even small amounts of alcohol can produce this pharmacologic response. It is important to remind persons taking disulfiram that alcohol can be absorbed by the body, even from common substances such as mouthwash or topical toners. This absorption can lead to a disulfiram-ethanol reaction, known as acetaldehyde syndrome.
History of Use
Disulfiram was discovered in the United States (US) 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 (FDA) 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.
In the twenty-first century, dosing recommendations 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 solely in persons with alcohol dependence, disulfiram also showed potential benefit in persons addicted to cocaine. Multiple clinical trials on the use of disulfiram for the treatment of cocaine dependence and methamphetamine dependence were completed. However, disulfiram is not approved for the treatment of any type of substance abuse besides alcohol, and other anti-addiction medications, such as methylphenidate and topiramate, have shown more promise. Disulfiram is estimated to be used by about two hundred thousand alcoholics in the US. 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 US. It is one of three drugs approved by the FDA for the treatment of alcohol dependence.
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. It 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 to 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.
Disulfiram continues to be a popular choice for treating alcohol use disorder (AUD). Although it has not proven as successful in treating cocaine and methamphetamine addictions as once previously thought, disulfiram is being investigated for its role as a therapeutic agent for other conditions, such as improving vision in people with retinitis pigmentosa. In the mid-2020s, several different medications aimed at people with AUD rose in popularity. GLP-1 Agonists, which rose to prominence as highly successful weight loss and diabetes drugs, also showed promise in treating AUD. The use of small doses of the psychedelic compound psilocybin may reduce alcohol cravings when administered in conjunction with cognitive behavioral therapy.
Bibliography
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