Can baclofen be used to treat acute alcohol withdrawal in adults, and what is the recommended dosing and safety monitoring?

Baclofen in Alcohol Withdrawal

Benzodiazepines remain the mandatory first-line treatment for acute alcohol withdrawal, and baclofen should not replace them; however, baclofen may serve as a useful adjunct to reduce benzodiazepine requirements or as an alternative in patients with severe hepatic impairment where benzodiazepines pose significant risks. 1

Primary Treatment Standard

Benzodiazepines are the only proven therapy that prevents alcohol withdrawal seizures and reduces mortality from delirium tremens, establishing them as the gold standard for acute alcohol withdrawal syndrome. 1, 2 Long-acting agents like diazepam (10 mg orally 3-4 times daily) or chlordiazepoxide (50-100 mg loading dose, then 25-100 mg every 4-6 hours) provide superior protection against seizures and delirium tremens compared to shorter-acting alternatives. 1

Baclofen's Role: Adjunct or Alternative

When Baclofen May Be Considered

Baclofen represents the only alcohol pharmacotherapy tested in patients with significant liver disease, including cirrhosis, making it uniquely valuable in this population where benzodiazepines carry substantial risks of oversedation and accumulation. 1

The 2018 EASL guidelines note that baclofen and sodium oxybate have been tested in the treatment of alcohol withdrawal syndrome, with the additional value that they are also being evaluated for treating alcohol use disorder itself. 1 The French ANSM has issued a temporary recommendation for baclofen use (not exceeding 80 mg/day) for alcohol use disorder treatment. 1

Evidence for Baclofen in Acute Withdrawal

A 2023 randomized controlled trial demonstrated that baclofen 60 mg/day significantly reduced the need for additional diazepam during alcohol detoxification: only 32% of patients on baclofen 60 mg/day required rescue diazepam compared to 72% on placebo (P = 0.013). 3 The median total diazepam requirement was significantly lower with both baclofen 60 mg/day (0 ± 10 mg) and baclofen 30 mg/day (0 ± 10 mg) compared to placebo (10 ± 43 mg; P = 0.017). 3

Another 2023 study found that gabapentin/baclofen combination resulted in significantly shorter hospital stays (42.6 vs 82.5 hours, P < 0.001) compared to benzodiazepines alone, with comparable safety profiles. 4

Important Limitations

However, a 2019 Cochrane systematic review concluded that no definitive conclusions can be drawn about baclofen's efficacy and safety for alcohol withdrawal management due to insufficient and very low-quality evidence. 5 The review included only four small RCTs with 189 participants, none of which reported the critical outcomes of withdrawal seizures, delirium tremens, or craving. 5

Practical Clinical Algorithm

Step 1: Risk Stratification

• Assess for severe hepatic impairment (cirrhosis, elevated bilirubin >3× normal, coagulopathy). 1
• Evaluate CIWA-Ar score: ≥8 indicates need for pharmacological treatment; ≥15 indicates severe withdrawal. 1

Step 2: Treatment Selection

For patients WITHOUT severe liver disease:

• Use benzodiazepines as first-line therapy (diazepam or chlordiazepoxide for most patients; lorazepam for elderly or mild hepatic dysfunction). 1, 2
• Consider baclofen 30-60 mg/day as adjunct if benzodiazepine requirements are escalating. 3

For patients WITH cirrhosis or severe liver disease:

• Short-acting benzodiazepines (lorazepam 2-4 mg every 4-6 hours) remain preferred, but use symptom-triggered dosing rather than fixed schedules. 1
• Baclofen 30-60 mg/day may be considered as an alternative when benzodiazepines pose unacceptable risks of accumulation or oversedation. 1, 3
• Note that over 70% of cirrhotic patients may not require benzodiazepines at all; use symptom-triggered approach. 1

Step 3: Mandatory Adjunctive Measures

• Administer thiamine 100-500 mg IV immediately BEFORE any glucose-containing fluids to prevent Wernicke encephalopathy. 1, 2
• Continue thiamine 100-300 mg/day for 2-3 months after withdrawal resolution. 1, 2
• Provide aggressive fluid and electrolyte replacement, especially magnesium supplementation. 2

Step 4: Duration and Tapering

• Limit benzodiazepine therapy to maximum 10-14 days to avoid iatrogenic dependence. 1, 2
• Begin tapering after approximately 96 hours when acute symptoms improve. 2

Dosing Recommendations

If using baclofen for alcohol withdrawal:

• Start with baclofen 30-60 mg/day divided into three doses (10-20 mg three times daily). 3
• The 60 mg/day dose showed superior efficacy in reducing benzodiazepine requirements. 3
• Do not exceed 80 mg/day per French ANSM recommendations. 1
• Baclofen was well tolerated with adverse events comparable to placebo in clinical trials. 3

Critical Pitfalls to Avoid

• Never use baclofen as monotherapy for moderate-to-severe withdrawal (CIWA-Ar ≥15) or in patients at risk for seizures or delirium tremens—benzodiazepines remain mandatory. 1, 2
• Never give glucose-containing IV fluids before thiamine, as this precipitates acute Wernicke encephalopathy. 1, 2
• Do not assume baclofen has proven efficacy for acute withdrawal; the evidence base remains very low quality despite promising recent trials. 5, 6
• Avoid naltrexone in patients with alcoholic liver disease due to hepatotoxicity risk. 1

Post-Withdrawal Relapse Prevention

After acute withdrawal stabilizes, baclofen becomes more clearly indicated for relapse prevention, as it is the only medication with demonstrated safety in cirrhotic patients for maintaining abstinence. 1 A clinical trial demonstrated safety and efficacy of baclofen in promoting alcohol abstinence in patients with alcoholic liver disease and cirrhosis, though confirmatory studies are warranted. 1

Mandatory psychiatric consultation after stabilization is required for comprehensive long-term abstinence planning, including consideration of relapse-prevention medications (acamprosate, baclofen, disulfiram, or topiramate—avoiding naltrexone in liver disease). 2