Disulfiram

• Alcohol Use Disorder
• Alcohol Dependence Treatment
• Aversion Therapy for Alcoholism
• Sobriety Maintenance

Disulfiram is an aldehyde dehydrogenase inhibitor used as an aversive agent in the management of alcohol use disorder. This medication creates an unpleasant reaction when alcohol is consumed, providing a deterrent to drinking and supporting abstinence in motivated patients undergoing treatment for alcohol dependence.

Mechanism of Action

Disulfiram irreversibly inhibits aldehyde dehydrogenase (ALDH), the enzyme responsible for metabolizing acetaldehyde to acetate in the liver. When a person taking disulfiram consumes alcohol, acetaldehyde accumulates in the blood, causing the disulfiram-ethanol reaction (DER). This reaction produces extremely unpleasant symptoms including flushing, throbbing headache, nausea, vomiting, sweating, thirst, chest pain, palpitations, dyspnea, hypotension, and confusion. The intensity of the reaction depends on the doses of both disulfiram and alcohol consumed. The aversive nature of this reaction is intended to deter alcohol consumption.

Available Formulations

Disulfiram is available as oral tablets in 250 mg and 500 mg strengths. The tablets are taken once daily, usually in the morning. The medication can be crushed and mixed with water, coffee, tea, or juice for patients who have difficulty swallowing tablets. Generic formulations are available.

Medical Uses

Disulfiram is FDA-approved as an aid in the management of selected chronic alcohol patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage. It is most effective in patients who are highly motivated to quit drinking and are participating in a comprehensive treatment program including counseling. The medication should not be used as the sole treatment but as part of a multimodal approach. Patients must abstain from alcohol for at least 12 hours before starting disulfiram.

Dosing Guidelines

The initial dose is 500 mg once daily for 1-2 weeks, followed by a maintenance dose of 250 mg daily (range: 125-500 mg daily). The maximum dose is 500 mg daily. Treatment should continue until the patient has established a basis for self-control. The duration of therapy is individualized and may range from months to years. Supervised administration (directly observed therapy) improves compliance. Patients should be informed that they must avoid all forms of alcohol (including hidden sources like mouthwash, sauces, vinegar, and over-the-counter medications).

Important Safety Information

Disulfiram should never be given to a patient who is intoxicated or without the patient's full knowledge and consent. The disulfiram-ethanol reaction can be severe and potentially fatal, especially in patients with cardiovascular disease. Severe reactions may cause respiratory depression, cardiovascular collapse, arrhythmias, MI, acute CHF, seizures, and death. Disulfiram should be used with extreme caution in patients with diabetes, hypothyroidism, epilepsy, cerebral damage, chronic or acute nephritis, or hepatic cirrhosis or insufficiency. Hepatotoxicity has been reported; liver function should be monitored.

Drug Interactions

Disulfiram inhibits the metabolism of many drugs. It increases the effects of warfarin, phenytoin, benzodiazepines, and caffeine. Concurrent use with metronidazole, isoniazid, or other drugs causing disulfiram-like reactions should be avoided. MAO inhibitors may cause hypertensive crisis. Disulfiram increases acetaldehyde levels from paraldehyde metabolism. Patients must avoid alcohol in any form, including hidden sources in foods, medications, and topical products.

Who Disulfiram Is Actually For

Disulfiram is not the first medication tried for alcohol use disorder, and the reason is mechanical rather than a judgment about severity. It does nothing for craving. It works only by making the consequence of drinking immediate and unpleasant, so its entire effect depends on the patient taking it on a morning when they have not yet decided whether to drink that evening. Naltrexone, which blunts the reward of drinking, and acamprosate, which helps with the restlessness and disturbed sleep of early abstinence, are usually tried first because neither asks for that daily act of commitment.

Disulfiram earns its place in a narrower situation: a patient whose goal is complete abstinence rather than reduced drinking, who wants an external barrier and understands what it does, and who has someone — a partner, a pharmacist, a clinic, sometimes an employer's program — willing to see the dose taken. Supervised administration changes outcomes more than any dose adjustment does. Where no supervision is available the tablet is easy to skip and the effect disappears with it. It is also the wrong choice when there is significant heart disease, advanced liver disease, psychosis, or continued heavy drinking at the time of the prescription.

The Conversation About Hidden Alcohol

Before the first tablet a patient needs a concrete list, not a general warning. Mouthwash, breath strips, cough and cold syrups, some liquid prescription medicines, vanilla and other flavoring extracts, wine or beer used in cooking where the dish is not fully cooked, kombucha, non-alcoholic beers that still contain a trace, certain vinegars, and sauces made with wine have all triggered reactions. So have some products applied to the skin, including alcohol-based aftershaves and heavy use of hand sanitizer in an enclosed space. The sensitivity does not end with the last tablet either: because the enzyme is blocked irreversibly and has to be replaced, a reaction remains possible for up to about two weeks after stopping, which matters when a patient plans to stop before a holiday or a wedding.

Liver enzymes are checked before starting and again during the early weeks, because the drug can injure the liver independently of any reaction with alcohol, and patients are told which symptoms — dark urine, yellowing of the eyes or skin, pain under the right ribs, unusual fatigue — mean a same-day call. Nobody should be given this medication covertly or while intoxicated. The MedlinePlus disulfiram monograph and the NIAAA guide to understanding alcohol use disorder set out the same points for patients, and our article on alcohol use disorder medications beyond AA compares the alternatives. Our psychiatric team is usually involved where mood or anxiety symptoms are driving the drinking.

Special Populations

Disulfiram is contraindicated during pregnancy; patients should use effective contraception during treatment. It is unknown whether disulfiram is excreted in breast milk; breastfeeding should be avoided. Safety and efficacy have not been established in pediatric patients. Elderly patients may be more sensitive to disulfiram effects. Disulfiram should be used with caution in patients with hepatic or renal impairment; hepatotoxicity can occur. Patients with psychosis or severe myocardial disease should not receive disulfiram.