Disulfiram
Aldehyde dehydrogenase inhibitor for alcohol relapse prevention
Disulfiram is an oral inhibitor of aldehyde dehydrogenase (ALDH) and is used for relapse prophylaxis after detoxification in alcohol dependence. The substance was launched in 1951 under the brand name Antabuse and is one of the oldest medicines for addiction treatment. The effect does not rely on a biological blockade of alcohol's action, but on an aversive reaction when alcohol is consumed. Alcohol consumption is thus psychologically burdened and hopefully avoided.
In Germany Antabuse has not been regularly marketed since 2011, but the substance can be obtained via international pharmacies or as a pharmacy compounded preparation. In other European countries and worldwide disulfiram remains more widely used. The drug is controversial: some experts see the aversive conditioning as an effective motivational tool, while others regard modern addiction medicine practice with naltrexone, acamprosate and nalmefene together with psychotherapeutic interventions as more appropriate and safer.
Mechanism of Action
Alcohol is broken down in the body in two main steps: first by alcohol dehydrogenase (ADH) to acetaldehyde, then by aldehyde dehydrogenase (ALDH) to acetate. Acetaldehyde is the intermediate responsible for many of the complaints caused by alcohol such as hangover symptoms. Normally it is broken down rapidly by ALDH so it does not accumulate.
Disulfiram and its active metabolites irreversibly inhibit mitochondrial ALDH. With alcohol intake acetaldehyde accumulates within minutes to 5 to 10 times normal values. The result is a pronounced disulfiram alcohol reaction with flush, heat sensation, tachycardia, hypotension, headache, nausea, vomiting, sweating and dyspnoea. The reaction starts 5 to 15 minutes after alcohol intake and can last several hours.
The half life of disulfiram itself is 60 to 120 hours; the metabolites bind ALDH for 1 to 2 weeks after discontinuation. A patient who takes disulfiram and drinks alcohol within this window experiences the aversive reaction even after stopping therapy. This psychological safety barrier is used therapeutically, but also represents a relevant risk in the case of accidental alcohol exposure.
Indications
- Relapse prophylaxis after qualified alcohol detoxification in motivated patients
- Support of abstinence within a comprehensive addiction therapy programme (psychotherapy, self help groups, social integration)
- Combination with other addiction medicine approaches in individual cases
Disulfiram is not a monotherapy but part of a multimodal treatment concept. Patients must be thoroughly informed, start therapy voluntarily and be aware of the reaction triggered by alcohol consumption. Disulfiram is not approved for opioid dependence or other substance use disorders.
Dosage and Administration
Initial phase: 400 mg once daily for 1 to 3 days to fully inhibit aldehyde dehydrogenase. Maintenance dose: 200 to 400 mg once daily, adjusted individually. The tablet is taken in the morning with or without a meal and swallowed with sufficient liquid.
Therapy should be started no earlier than 24 to 48 hours after the last alcohol intake. Full aldehyde dehydrogenase inhibition is reached after 12 to 24 hours. A disulfiram alcohol reaction can occur with very small amounts of alcohol, including alcohol from mouthwashes, disinfectants, some medicines or fermented foods.
Treatment duration depends on individual motivation, relapse risk and therapeutic setting. Several months up to a year with regular medical and psychotherapeutic support are common. Renal impairment: no dose adjustment. Hepatic impairment: contraindicated in severe impairment. Elderly patients: caution, because the disulfiram alcohol reaction can be more severe in older people.
Side Effects
Without alcohol, common: metallic taste or garlic like breath odour, fatigue, headache, dizziness, nausea, diarrhoea, skin rash, reduced libido, reduced potency.
Without alcohol, uncommon to rare: peripheral neuropathy (usually reversible after discontinuation), hepatotoxicity with potentially fulminant liver failure, psychiatric changes (depression, psychosis, confusion in older patients), optic neuritis, allergic skin reactions, blood count changes.
Disulfiram alcohol reaction: flushing, intense heat waves, tachycardia, hypotension, severe headache, nausea, vomiting, shortness of breath, dyspnoea, anxiety, dizziness. In severe cases circulatory collapse, myocardial infarction, stroke or respiratory depression, particularly in patients with pre existing cardiovascular disease. The reaction usually lasts several hours and often requires emergency medical monitoring.
Interactions
- Alcohol: severe disulfiram alcohol reaction, avoidance is mandatory
- Alcohol containing medicines and tinctures: reaction possible, even in small amounts
- Alcohol containing mouthwashes, disinfectants, cosmetics: reaction possible due to absorption through skin or mucous membranes
- Metronidazole, cefotetan, tinidazole: own disulfiram like effect, avoid combination
- Phenytoin, carbamazepine: delayed metabolism, toxicity risk
- Warfarin, phenprocoumon: enhanced anticoagulant effect, check INR
- Benzodiazepines, tricyclic antidepressants: slowed elimination, enhanced effect
- Isoniazid, amitriptyline: intensified central nervous system side effects
- Paraldehyde, theophylline: also increased toxicity
Special Notes
Contraindications: severe cardiovascular disease (coronary artery disease, heart failure, previous myocardial infarction), severe hepatic impairment, severe renal impairment, severe psychiatric illness such as psychosis or severe depression, pregnancy, breastfeeding, hyperthyroidism, active alcohol use at the start of therapy, known hypersensitivity.
Informed consent: patients must be comprehensively informed about the disulfiram alcohol reaction and consent voluntarily to therapy. The patient should carry a medication card or emergency card so that in an emergency treating doctors are aware of ongoing disulfiram therapy.
Multimodal therapy: disulfiram only works if the medication is actually taken. Efficacy is greatest in supervised settings (observed intake by relatives, pharmacy or therapist). Taken alone and without psychotherapeutic support, the effect is limited. Modern alternatives such as naltrexone (mu opioid antagonist), acamprosate (NMDA and GABA modulation), nalmefene (on demand opioid antagonist) and context oriented psychotherapy are now often the preferred first line.
Pregnancy and breastfeeding: contraindicated because of teratogenic and toxic effects. If pregnancy is planned, switch therapy in good time and provide multidisciplinary support.
Monitoring: liver values before therapy, after 14 days, after 6 weeks, then every 3 months. If hepatotoxicity is suspected (jaundice, dark urine, fatigue, nausea) stop therapy immediately and investigate clinically. Neurological examination if neuropathy or psychosis is suspected.
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Frequently Asked Questions
What happens if I drink alcohol while on disulfiram?
Aldehyde dehydrogenase inhibition leads within 10 to 15 minutes to a disulfiram alcohol reaction with heat sensation, headache, tachycardia, hypotension, nausea and shortness of breath. The reaction lasts several hours and can become life threatening with high alcohol amounts or pre existing cardiac disease. In severe symptoms call the emergency number 112.
How long does the effect last after discontinuation?
Aldehyde dehydrogenase inhibition persists for 1 to 2 weeks after the last dose. Anyone who consumes alcohol during this window experiences the aversive reaction. This long after effect is therapeutically intended, but must be considered in planned pauses or at the end of therapy.
Is disulfiram still available in Germany?
Antabuse has not been regularly marketed in Germany since 2011. The substance can be imported via international pharmacies or prepared as a pharmacy compounded formulation. Modern addiction medicine, however, more often uses alternatives such as naltrexone, acamprosate or nalmefene.
Are small amounts of alcohol enough for a reaction?
Yes. Even the smallest amounts of alcohol from mouthwashes, disinfectants, hair tonics, tinctures, cough syrups and fermented foods can trigger a reaction. Patients must check all products for alcohol content and avoid them where possible. Doctors should check all concomitant medicines for alcohol as an excipient.
Sources
- EMA, European Medicines Agency
- AWMF, S3 Guideline Alcohol Related Disorders
- Gelbe Liste, Disulfiram active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
Legal Notice and Disclaimer
The information provided on this page is for general informational purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace consultation with a licensed physician or pharmacist. Medicines should only be taken on medical prescription or via a pharmacy. All information is based on product information and recognised scientific sources published at the time of creation; the manufacturer's current summary of product characteristics is always authoritative. Sanoliste assumes no liability for the completeness, timeliness or accuracy of the information presented. In a medical emergency, call the emergency number 112 (Europe).