Disulfiram: A Proven Pharmacological Adjunct for Alcohol Use Disorder
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Synonyms | |||
Disulfiram is an aversive pharmacological agent indicated as an adjunct in the management of chronic alcohol use disorder. Its primary mechanism of action is the inhibition of aldehyde dehydrogenase (ALDH), an enzyme critical in the metabolism of ethanol. By disrupting the normal metabolic pathway, disulfiram produces a highly unpleasant physiological reaction upon alcohol consumption, thereby acting as a psychological deterrent. This product card provides a comprehensive, evidence-based overview for healthcare professionals to support informed clinical decision-making and patient counseling.
Features
- Active Pharmaceutical Ingredient: Disulfiram.
- Standard Tablet Strengths: 250 mg and 500 mg.
- Mechanism of Action: Irreversible inhibition of the mitochondrial enzyme aldehyde dehydrogenase (ALDH1A1).
- Pharmacokinetics: Rapidly absorbed from the GI tract; undergoes complex metabolism and is reduced to its active form, diethyldithiocarbamate.
- Duration of Pharmacological Effect: The ALDH inhibition effect can persist for up to 14 days following discontinuation of therapy due to the time required for enzyme regeneration.
- Formulation: Oral tablets.
Benefits
- Creates a powerful psychological deterrent to alcohol consumption by establishing a direct, negative association between drinking and adverse physical effects.
- Supports long-term abstinence goals by providing a tangible pharmacological barrier during the critical period of behavioral therapy and counseling.
- Empowers patients within a structured treatment plan, offering a sense of control and a concrete tool to resist cravings and social pressures.
- Facilitates the development of new, sober habits and coping mechanisms by reducing the frequency of impulsive drinking episodes.
Common use
Disulfiram is exclusively indicated as an adjunct to comprehensive psychosocial therapy for the maintenance of abstinence in patients seeking treatment for chronic alcohol dependence. It is not indicated for the treatment of acute alcohol intoxication or alcohol withdrawal syndrome. Its use is predicated on the patient’s full, informed consent and a clear understanding of the consequences of alcohol ingestion while the drug is in their system. Ideal candidates are highly motivated individuals committed to sobriety and engaged in a supervised treatment program.
Dosage and direction
Initialization: Treatment should only be initiated after the patient has abstained from alcohol for at least 12 hours and a baseline transaminase level has been established to rule out pre-existing hepatic impairment. A common initial dosage is 500 mg daily for one to two weeks. Maintenance: The dosage should be individually titrated to the lowest effective level. A typical maintenance dose ranges from 125 mg to 500 mg daily. Doses exceeding 500 mg daily are not recommended due to an increased risk of adverse events without a proportional increase in efficacy. Administration: The tablet should be taken orally once daily, preferably in the morning. It can be crushed and mixed with liquid if necessary. The duration of therapy is individualized and may continue for months or even years, contingent upon the patient’s progress within their overall treatment plan.
Precautions
- Hepatic Monitoring: Baseline and periodic (e.g., every 3-6 months) monitoring of liver function tests (transaminases, bilirubin) is mandatory due to the risk of disulfiram-induced hepatitis, which can be fatal.
- Neuropathy: Patients should be advised to report any symptoms of peripheral neuropathy, such as tingling or weakness in the extremities, promptly. This may necessitate discontinuation.
- Psychiatric Effects: Can rarely cause psychotic reactions, mood disturbances, and confusion. Patients with a history of psychosis or severe psychiatric disorders should be monitored closely.
- Informed Consent: The patient must be fully educated on the disulfiram-ethanol reaction (DER), its risks, and the necessity of avoiding all sources of alcohol, including hidden sources in foods, medications (e.g., elixirs, mouthwashes), and toiletries.
- Pregnancy and Lactation: Disulfiram is contraindicated in pregnancy (Pregnancy Category C). It is not recommended for use in nursing mothers.
Contraindications
- Severe myocardial disease or coronary occlusion.
- Psychosis or severe intellectual impairment where the patient cannot comprehend the therapy’s consequences.
- Hypersensitivity to disulfiram or other thiuram derivatives used in pesticides or rubber vulcanization.
- Concurrent or recent (within 12 hours) use of alcohol or alcohol-containing products.
- Concomitant therapy with metronidazole, paraldehyde, or any drug that can produce a disulfiram-like reaction.
Possible side effect
Common:
- Drowsiness, fatigue, headache, and metallic or garlic-like aftertaste are frequently reported, especially during the initial weeks of therapy. These often subside with continued use.
- Acneiform eruptions and mild allergic dermatitis. Serious (require immediate medical evaluation):
- Signs of hepatitis: jaundice, dark urine, clay-colored stools, right upper quadrant pain.
- Symptoms of peripheral neuropathy: paresthesia, weakness, or motor paralysis.
- Optic neuritis: blurred vision or changes in visual acuity.
- Psychiatric effects: depression, paranoia, manic episodes, or confusion.
Drug interaction
Disulfiram inhibits several hepatic microsomal enzymes, notably CYP2E1 and CYP2C9, and can alter the metabolism of numerous concomitant medications, potentially leading to increased serum levels and toxicity.
- Warfarin: Potentiates anticoagulant effect; prothrombin time must be monitored closely and warfarin dosage reduced.
- Phenytoin: Significantly increases phenytoin levels, increasing the risk of phenytoin toxicity (nystagmus, ataxia, drowsiness).
- Benzodiazepines: Metabolism of certain benzodiazepines (e.g., chlordiazepoxide, diazepam) may be impaired.
- Tricyclic Antidepressants: Metabolism may be inhibited, potentially leading to increased anticholinergic and sedative effects.
- Isoniazid: Increased risk of neurotoxic side effects and dizziness.
- Theophylline: May decrease theophylline clearance, increasing the risk of toxicity.
Missed dose
If a dose is missed, it should be taken as soon as remembered on the same day. If it is not remembered until the next day, the patient should skip the missed dose and resume the regular dosing schedule. The patient must never double the dose to make up for a missed one. The protective effect against alcohol diminishes approximately 14 days after the last dose.
Overdose
Overdose is rare but can be severe. Symptoms may include nausea, vomiting, dizziness, ataxia, lethargy, seizures, and neuropsychiatric disturbances. In severe cases, cardiovascular collapse, respiratory depression, and coma may occur. Management is primarily supportive and symptomatic. There is no specific antidote. Gastric lavage may be considered if presentation is early. Support of respiratory and cardiovascular function is paramount.
Storage
Store at controlled room temperature (20°C to 25°C or 68°F to 77°F), in a tight, light-resistant container. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging.
Disclaimer
This information is intended for educational purposes for healthcare professionals and is not a substitute for professional clinical judgment. The prescriber must reference the full manufacturer’s prescribing information before initiating therapy. Dosage and treatment decisions are the sole responsibility of the prescribing physician, based on the individual patient’s clinical status and treatment goals.
Reviews
“Disulfiram remains a cornerstone agent in our addiction medicine toolkit. Its efficacy is almost entirely dependent on patient adherence and the context of a robust therapeutic alliance. For the motivated patient, it is an unparalleled deterrent. The key to its safe use is rigorous patient selection, exhaustive education, and diligent monitoring for hepatic and neurological sequelae.” – Addiction Psychiatrist, 15 years of experience.
“In my practice, disulfiram is most effective when used as a ‘contract’ between the patient and their support system. The fear of the reaction provides a concrete reason to refuse a drink in socially challenging situations, buying time for cognitive behavioral strategies to engage. However, the potential for serious adverse effects mandates that it be prescribed with great caution and only after a thorough risk-benefit analysis.” – Certified Addiction Registered Nurse, outpatient clinic.