What is the use of Disulfiram (Antabuse) in the treatment of chronic alcoholism in adult patients?

Disulfiram Use in Chronic Alcoholism

Disulfiram is FDA-approved as an adjunctive treatment for motivated chronic alcoholics who desire enforced sobriety, but it should NOT be used in patients with alcoholic liver disease due to hepatotoxicity risk. 1, 2, 3, 4

Mechanism of Action

Disulfiram blocks acetaldehyde dehydrogenase, causing acetaldehyde accumulation (5-10 times normal levels) when alcohol is consumed, producing an intensely unpleasant reaction that serves as a deterrent to drinking. 4 The drug does not influence alcohol elimination rate but creates increasing sensitivity over time—the longer a patient takes disulfiram, the more sensitive they become to alcohol. 4

Clinical Indications and Patient Selection

Disulfiram is appropriate only for:

• Patients with chronic alcohol use disorder who are highly motivated to maintain abstinence 4
• Patients without liver disease (specifically, those without alcoholic liver disease or hepatic cirrhosis/insufficiency) 1, 4
• Patients who can participate in concurrent psychosocial treatment and structured supervision 4, 5
• Patients who are older, more socially stable, and well-motivated may benefit most 5

Disulfiram is NOT a cure for alcoholism and is ineffective when used alone without proper motivation and supportive therapy. 4

Absolute Contraindications

• Alcoholic liver disease or hepatic cirrhosis/insufficiency (the American Association for the Study of Liver Diseases explicitly excludes disulfiram from their treatment table and states it is not recommended for patients with ALD) 1
• Severe alcoholic liver disease due to possible hepatotoxicity 2, 3
• Current alcohol intoxication 4
• Diabetes mellitus, hypothyroidism, epilepsy, cerebral damage, chronic/acute nephritis 4

Dosing and Administration

• Standard dosing: 250-500 mg/day orally 5, 6
• Lower doses (25 mg/kg in animal models) can achieve aldehyde dehydrogenase inhibition without neurotoxic effects on brain catecholamines 6
• The drug must never be given without the patient's full knowledge and informed consent 4

Critical Patient Education Requirements

Patients must be warned about:

• The disulfiram-alcohol reaction can occur with even small amounts of alcohol (as little as 5-10 mg/100 mL blood alcohol) 4
• Reactions persist up to 14 days after the last disulfiram dose 4
• Hidden alcohol sources: sauces, vinegars, cough mixtures, aftershave lotions, back rubs 4
• Reaction symptoms: flushing, throbbing headache, respiratory difficulty, nausea, copious vomiting, chest pain, palpitations, hypotension, syncope, blurred vision, confusion 4
• Severe reactions: respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute heart failure, unconsciousness, convulsions, death 4

Expected Efficacy

• Probably effective in reducing frequency of alcohol consumption in compliant patients over short-term (approximately 6 months) 5
• Most effective when compliance is supervised 5
• No proven effect on long-term outcome of alcoholism 5
• In patients with severe mental illness, 64% achieved one-year remission and 30% achieved two-year remission during three-year follow-up 7

Preferred Alternatives for Patients with Liver Disease

For patients with alcoholic liver disease, use these alternatives instead:

• Baclofen 30-60 mg/day is the only medication specifically studied and proven safe in patients with compensated and decompensated cirrhosis 1, 2, 3
• Acamprosate 666 mg three times daily has no hepatic metabolism and no hepatotoxicity risk (NNT = 12) 1, 3
• Gabapentin 600-1,800 mg/day is safe in severe liver disease with no hepatotoxicity risk 2, 3

Essential Treatment Framework

Disulfiram must be combined with:

• Structured, supervised aftercare program 5
• Psychosocial interventions (cognitive-behavioral therapy, motivational interviewing, motivational enhancement therapy) 1, 2
• Regular clinical supervision and monitoring for efficacy and side effects 5
• Education and counseling 5

Prescription of disulfiram without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. 5

Psychiatric Considerations

At standard dosing (250 mg/day), disulfiram does not significantly increase risk of psychiatric complications or drug interactions, making it a reasonable option for patients with comorbid psychiatric disorders. 8 In patients with severe mental illness and alcoholism, significant psychiatric complications were not reported, though 21% experienced side effects. 7

Common Pitfall to Avoid

The most critical error is prescribing disulfiram to patients with any degree of alcoholic liver disease—this population requires baclofen, acamprosate, or gabapentin instead, as these medications lack hepatotoxicity risk and have been studied in liver disease populations. 1, 2, 3