What is the recommended pharmacologic regimen for treating acute alcohol withdrawal in adults, including dosing, choice of benzodiazepine based on liver function, and adjunctive therapies?

Alcohol Withdrawal Medication

First-Line Pharmacologic Treatment

Benzodiazepines are the mandatory first-line therapy for acute alcohol withdrawal—they are the only proven treatment that prevents seizures and reduces mortality from delirium tremens. 1

Benzodiazepine Selection Based on Liver Function

For patients WITHOUT hepatic dysfunction:

• Long-acting benzodiazepines provide superior protection against seizures and delirium tremens compared to shorter-acting agents 1, 2
• Diazepam is the preferred agent due to its shortest time to peak effect (facilitating rapid symptom control) and longest elimination half-life (providing smoother, self-tapering withdrawal with lower breakthrough symptoms) 3
  • Dosing: 10 mg PO/IV initially, then 5–10 mg every 6–8 hours 1, 2
• Chlordiazepoxide is an alternative long-acting option 1
  • Dosing: 50–100 mg PO loading dose, then 25–100 mg every 4–6 hours (maximum 300 mg in first 24 hours) 1

For patients WITH hepatic dysfunction, elderly, respiratory compromise, or obesity:

• Short-acting benzodiazepines are preferred to avoid drug accumulation and excessive sedation 1, 2
• Lorazepam is the agent of choice in these populations 1, 2
  • Dosing: 2–4 mg PO/IV/IM every 4–6 hours (total 6–12 mg/day) 1, 2
• Oxazepam may be used as an alternative 1

Important caveat: The fear of over-sedation with diazepam in liver disease is based on misunderstanding of pharmacokinetics; symptom-triggered dosing with diazepam is safe when monitored appropriately, and the superiority of short-acting agents in liver disease is not validated by controlled trials 4, 3

Symptom-Triggered vs. Fixed-Schedule Dosing

• Use the CIWA-Ar scale to guide treatment intensity: scores ≥8 indicate need for pharmacologic treatment; scores ≥15 denote severe withdrawal requiring aggressive management 1, 2
• Over 70% of cirrhotic patients may not require benzodiazepines at all—use symptom-triggered dosing only when CIWA-Ar ≥8 rather than prophylactic fixed schedules 1, 4

Duration and Tapering

• Limit total benzodiazepine therapy to a maximum of 10–14 days to avoid iatrogenic dependence 1, 4, 2
• Begin tapering long-acting benzodiazepines after approximately 96 hours (day 4) when acute symptoms are improving 1
  • Reduce daily dose by approximately 25% every 2–3 days for long-acting agents 1
  • Reduce by 10–25% every 2–4 days for short-acting agents 1
• Never discontinue abruptly—always taper gradually 1

Mandatory Thiamine Administration

Administer thiamine 100–500 mg IV immediately BEFORE any glucose-containing fluids to prevent precipitating acute Wernicke encephalopathy—this is mandatory for every patient with alcohol withdrawal 1, 4, 2

• Continue thiamine 100–300 mg/day (oral or IV) throughout withdrawal and for 2–3 months after resolution 1, 4
• Thiamine deficiency is present in 30–80% of alcohol-dependent patients 4

Essential Supportive Care

• Aggressive fluid and electrolyte replacement with particular attention to magnesium supplementation is essential, as magnesium is commonly depleted in chronic alcohol use 1
• Continuous vital-sign monitoring for autonomic instability (tachycardia, hypertension, fever, diaphoresis) 1, 4
• Screen for dangerous complications: dehydration, electrolyte imbalance, infection (pneumonia, spontaneous bacterial peritonitis), gastrointestinal bleeding, pancreatitis, hepatic encephalopathy 1, 4

Adjunctive Therapies

For Severe Withdrawal or Delirium Tremens

• Haloperidol 0.5–5 mg PO/IM may be added ONLY as adjunctive therapy for severe agitation or hallucinations not controlled by adequate benzodiazepine dosing 1, 4
• Never use antipsychotics as monotherapy—they lower seizure threshold and worsen outcomes 1, 4

For Benzodiazepine-Refractory Cases (ICU Setting)

• Phenobarbital or propofol can be used as second-line sedative agents in severe withdrawal inadequately controlled with benzodiazepines 1, 5
• Dexmedetomidine serves as adjunctive therapy only for severe, benzodiazepine-refractory cases but does not prevent seizures or delirium tremens 1

Beta-Blockers

• Intravenous beta-blockers (e.g., propranolol) can be added for persistent tachycardia despite adequate benzodiazepines, but never as monotherapy because they do not prevent seizures or delirium tremens 1

Carbamazepine

• Carbamazepine 200 mg PO every 6–8 hours may be used as a benzodiazepine-sparing agent in patients with severe hepatic impairment or benzodiazepine-use disorder 1, 2
• CIWA-Ar ≥15 is an absolute contraindication to carbamazepine monotherapy—benzodiazepines remain mandatory 1
• Never use carbamazepine as monotherapy for moderate-to-severe withdrawal or in patients at risk for seizures 1

Baclofen

• Baclofen (up to 80 mg/day) is the only medication with proven safety in cirrhotic patients and can be used as an alternative when benzodiazepines pose unacceptable risks of accumulation 1, 4
• Never use baclofen as monotherapy for moderate-to-severe withdrawal (CIWA-Ar ≥15)—benzodiazepines remain mandatory 1

Medications to AVOID

• Anticonvulsants (phenytoin, carbamazepine) should NOT be used to prevent alcohol-withdrawal seizures—they are ineffective and may worsen outcomes 1, 4, 2
• Naltrexone is contraindicated in alcoholic liver disease due to hepatotoxicity risk 1, 4

Inpatient vs. Outpatient Decision

Admit to hospital if ANY of the following are present: 1, 4

• Prior withdrawal seizures or delirium tremens
• Severe current symptoms (tremor with vomiting, CIWA-Ar ≥15)
• Chronic heavy drinking >80 g/day for ≥10 years
• Serious medical comorbidities (liver disease, infection, pancreatitis, GI bleeding, cardiovascular disease)
• Serious psychiatric illness or active suicide risk
• Inadequate social support or unstable housing
• Failure of prior outpatient treatment
• Malnutrition or suspected Wernicke encephalopathy

Outpatient treatment is appropriate for mild-to-moderate withdrawal (CIWA-Ar <15) without complications, with daily physician visits for 3–5 days after last drink 1

Post-Acute Relapse Prevention

Mandatory psychiatric consultation after stabilization for evaluation of alcohol-use disorder severity and long-term abstinence planning 1, 4

Evidence-based relapse-prevention medications (initiated AFTER withdrawal completion): 1, 4

Medication	Dosing	Key Considerations
Acamprosate	≈2 g/day for patients ≥60 kg	Safe in liver disease; reduces craving
Baclofen	Up to 80 mg/day	Only medication proven safe in cirrhosis
Naltrexone	25 mg × 1–3 days, then 50 mg daily	CONTRAINDICATED in alcoholic liver disease
Disulfiram	500 mg daily × 1–2 weeks, then 125–500 mg daily	CONTRAINDICATED in severe liver disease
Topiramate	Variable dosing	Emerging evidence for relapse prevention

Encourage engagement with Alcoholics Anonymous or similar mutual-help groups 1, 4

Critical Pitfalls to Avoid

• Never give glucose-containing IV fluids before thiamine—this can precipitate acute Wernicke encephalopathy 1, 4
• Never rely on anticonvulsants alone for seizure prevention—benzodiazepines are mandatory 1, 4
• Never use antipsychotics as monotherapy—they increase seizure risk 1, 4
• Never extend benzodiazepine therapy beyond 14 days or discontinue abruptly 1, 4
• Do not assume all cirrhotic patients require benzodiazepines—use symptom-triggered dosing 1, 4
• Dispense benzodiazepines in small quantities or supervise each dose to minimize misuse risk 1, 4

Timeline of Withdrawal Symptoms

• 6–24 hours: Tremor, sweating, tachycardia, hypertension, nausea, vomiting, anxiety 1, 6
• 12–48 hours: Seizures (occur in up to 15% of patients) 1, 6
• 48–72 hours (peak days 3–5): Delirium tremens (confusion, severe autonomic instability)—mortality ≈50% if untreated 1, 6
• Up to 1 week: Resolution of symptoms (may persist up to 2 weeks) 1, 6