Alcohol Withdrawal Pharmacotherapy

Alcohol withdrawal begins 6 to 24 hours after the last drink, with seizures at 12 to 48 hours and delirium tremens at 48 to 96 hours, with hallucinations, autonomic instability and a mortality of several percent if untreated. Treatment uses benzodiazepines, thiamine and correction of electrolytes.

Assessment. Use a structured score, such as the CIWA-Ar, with treatment for a score of 10 or more. Identify risk factors for severe withdrawal: previous seizures or delirium tremens, a high daily intake, and concurrent illness.

Thiamine first. Give thiamine before or with glucose. Wernicke encephalopathy (confusion, ataxia, ophthalmoplegia) is treated at high dose.

First line. A long-acting benzodiazepine: chlordiazepoxide in a reducing fixed dose, or diazepam, either fixed or symptom-triggered.

Liver failure or older adults. Lorazepam or oxazepam, which have no active metabolites.

Seizures. Benzodiazepines. Phenytoin is ineffective for withdrawal seizures.

Delirium tremens resistant to benzodiazepines. Phenobarbital, or propofol or dexmedetomidine in intensive care. Haloperidol is an adjunct for hallucinations only.

Relapse prevention (after detoxification). Naltrexone or acamprosate.

Special groups.

• Pregnancy: inpatient treatment with obstetric advice.

• Older adults: lower doses and shorter-acting drugs.

• Liver disease: lorazepam, with caution.

• East Africa: locally produced or illicit alcohol may be contaminated with methanol, so consider methanol poisoning (visual disturbance, severe acidosis) in any patient with unexplained acidosis.

• Thiamine prophylaxis: 100 mg orally three times daily, or 250 mg intravenously daily for 3 to 5 days.

• Thiamine for Wernicke encephalopathy: 500 mg intravenously over 30 minutes three times daily for 2 to 3 days, then 250 mg once daily for 3 to 5 days.

• Chlordiazepoxide: 20 to 30 mg four times daily on days 1 and 2, reduced over 5 to 7 days.

• Diazepam: 10 to 20 mg orally or intravenously every 1 to 2 hours until calm (symptom-triggered), then reduce.

• Lorazepam: 1 to 2 mg orally or intravenously every 4 to 6 hours in liver failure.

• Seizures: lorazepam 4 mg intravenously, or diazepam 10 mg intravenously, repeated once.

• Delirium tremens: diazepam 10 mg intravenously every 5 to 10 minutes until calm. Phenobarbital 10 mg/kg intravenously for resistant cases in monitored settings.

• Haloperidol: 0.5 to 5 mg for hallucinations, only after a benzodiazepine.

• Folic acid: 5 mg once daily.

• Naltrexone: 50 mg once daily (avoid with opioids and in liver failure). Acamprosate 666 mg three times daily (333 mg three times daily when creatinine clearance is 30 to 50 mL/min, avoid under 30).

Monitoring. CIWA-Ar every 1 to 2 hours at first, vital signs, sedation, glucose, and potassium, magnesium, phosphate and sodium daily. Replace magnesium and potassium.

Stop rules. Reduce and stop the benzodiazepine over 5 to 7 days as symptoms resolve. Stop for oversedation or respiratory depression.

Referral and escalation. Seek intensive care for delirium tremens, seizures not controlled, need for over 200 mg of diazepam (or equivalent) in the first 3 hours, respiratory depression, or severe autonomic instability. Refer to addiction services for relapse prevention.

Common errors. Giving glucose before thiamine, using phenytoin for withdrawal seizures, under-dosing benzodiazepines, using haloperidol alone, and missing hypomagnesaemia.