Drugs for Alcohol Use Disorder

Drugs for alcohol use disorder treat withdrawal, prevent Wernicke encephalopathy and reduce relapse or drinking. They are added to psychosocial support, which remains the base of treatment.

Mechanism. Benzodiazepines replace the GABA effect lost in withdrawal. Naltrexone and nalmefene block opioid receptors and blunt alcohol reward. Acamprosate modulates glutamate and GABA signalling. Disulfiram inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation when alcohol is taken. Baclofen is a GABA-B agonist.

Pharmacokinetics. Naltrexone is metabolised in the liver to an active metabolite. Acamprosate is cleared unchanged by the kidney. Disulfiram effect lasts up to 2 weeks after the last dose.

Differences. Acamprosate suits abstinence goals and liver disease. Naltrexone and nalmefene suit reduction goals. Disulfiram requires a committed, supervised patient.

• Withdrawal: symptom-triggered or fixed-dose benzodiazepine tapering, with thiamine and correction of magnesium, potassium and glucose. Use lorazepam in severe liver disease or older adults.
• Relapse prevention after detoxification: acamprosate or naltrexone for 6 to 12 months, with psychosocial care.
• Liver disease: acamprosate, or baclofen with caution; avoid disulfiram and, in acute hepatitis or failure, naltrexone.
• Disulfiram: start 24 hours or more after the last drink; warn about reactions to alcohol in syrups, mouthwash and topical products, and with metronidazole.
• Opioid users: do not give naltrexone or nalmefene, as they cause withdrawal.

Special groups. Pregnancy: avoid drugs for relapse prevention; use thiamine and psychosocial care. Breastfeeding: avoid. Children and adolescents: specialist use. Older adults: lower benzodiazepine doses. Kidney impairment: reduce or avoid acamprosate (contraindicated at creatinine clearance under 30 mL/min). Liver impairment: reduce benzodiazepine doses and avoid disulfiram. Regional: unrecorded and illicit spirits may contain methanol, causing acidosis and blindness, which needs urgent toxic alcohol treatment.

Adverse effects. Benzodiazepines: oversedation and respiratory depression. Naltrexone: nausea, headache, dizziness and liver enzyme rise. Acamprosate: diarrhoea and nausea. Disulfiram: drowsiness, metallic taste, hepatitis, neuropathy, psychosis, and the disulfiram-alcohol reaction (flushing, palpitations, hypotension). Baclofen: sedation and confusion.

Contraindications. Naltrexone with opioid use or acute liver failure. Acamprosate with severe renal impairment. Disulfiram with heart disease, psychosis, liver disease and pregnancy.

Interactions. Opioid analgesics (blocked by naltrexone), warfarin and phenytoin (levels rise with disulfiram), metronidazole.

Monitoring. Liver enzymes at baseline and during therapy, creatinine, blood alcohol or drinking diary, and mood.

Referral and escalation. Seizures or delirium tremens, suspected Wernicke encephalopathy, severe liver disease, or suicidal intent.