What are the first‑line pharmacologic agents, their dosing, and contraindications for reducing alcohol consumption in adults with alcohol‑use disorder?

First-Line Pharmacologic Agents for Alcohol Use Disorder

For adults with alcohol use disorder and normal liver function, initiate naltrexone 50 mg daily or acamprosate 666 mg three times daily, combined with evidence-based psychosocial therapy; for patients with alcoholic liver disease or cirrhosis, baclofen is the only validated option. 1, 2, 3

Patient Assessment Before Initiating Therapy

Essential Laboratory Screening

• Obtain baseline liver function tests (AST, ALT, bilirubin) and assess for alcoholic liver disease, acute hepatitis, or cirrhosis before prescribing any medication 3
• Check creatinine clearance because acamprosate requires dose adjustment or is contraindicated when renal function is impaired 3
• Verify the patient is opioid-free (including tramadol) for a minimum of 7-10 days before starting naltrexone to avoid precipitated withdrawal 4

Withdrawal Status Verification

• Never initiate naltrexone, acamprosate, or baclofen during active alcohol withdrawal 3
• Manage acute withdrawal with benzodiazepines first—lorazepam 1-4 mg every 4-8 hours in patients with liver dysfunction, or diazepam/chlordiazepoxide in those without hepatic impairment 2, 3
• Administer thiamine 100-300 mg daily for 4-12 weeks before any glucose-containing IV fluids to prevent Wernicke encephalopathy 2, 3
• Wait 3-7 days after the last drink and complete resolution of withdrawal symptoms before starting maintenance pharmacotherapy 3

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First-Line Medications for Patients WITHOUT Liver Disease

Naltrexone (Harm-Reduction Focus)

Dosing Algorithm:

• Start 25 mg orally daily for days 1-3, then increase to 50 mg daily 3, 4
• Continue for 3-6 months, up to 12 months 3
• Alternative: Extended-release injectable naltrexone 380 mg intramuscularly monthly 3

Mechanism & Efficacy:

• Opioid receptor antagonist that reduces heavy-drinking episodes and overall drinking frequency more effectively than it promotes complete abstinence 3
• Number needed to treat (NNT) = 20 to prevent any drinking 1, 3
• Reduces binge-drinking risk by 10% 5

Monitoring & Safety:

• Monitor liver enzymes every 3-6 months during treatment 3
• Naltrexone is metabolized hepatically and carries hepatotoxicity risk at therapeutic doses 3
• Absolutely contraindicated in alcoholic liver disease, acute hepatitis, decompensated cirrhosis, or any elevation of liver enzymes 1, 2, 3

Critical Pitfall:

• Initiating naltrexone during active withdrawal can precipitate hyper-acute withdrawal syndrome due to opioid-receptor antagonism 3

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Acamprosate (Abstinence Focus)

Dosing Algorithm:

• 666 mg orally three times daily (total ≈2000 mg/day) for patients ≥60 kg 1, 3
• Initiate 3-7 days after the last drink, once withdrawal has resolved 3
• Continue for 3-6 months minimum 1

Mechanism & Efficacy:

• NMDA receptor antagonist that stabilizes glutamatergic systems dysregulated by chronic alcohol intake 1
• NNT = 12 for achieving abstinence 1, 3
• Meta-analysis of 24 randomized controlled trials confirms efficacy equal to naltrexone 3

Safety Profile:

• No hepatic metabolism and zero hepatotoxicity risk—safe in any degree of liver disease 1, 3
• No reported instances of hepatotoxicity in clinical use 1
• Preferred when hepatic status is uncertain 3

Renal Considerations:

• Eliminated unchanged by the kidneys 3
• Contraindicated in severe renal impairment (CrCl ≤30 mL/min) 3
• Dose-reduce for moderate impairment (CrCl 30-50 mL/min) 3

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First-Line Medication for Patients WITH Alcoholic Liver Disease or Cirrhosis

Baclofen (Only Validated Option in Cirrhosis)

Dosing Algorithm:

• Start 10 mg orally three times daily (30 mg total) 1, 3
• Titrate gradually over 12 weeks to 30-80 mg/day 3
• Use slower titration in severe liver disease 3

Evidence Base:

• Baclofen is the only medication with proven safety and efficacy in randomized controlled trials specifically enrolling patients with compensated and decompensated cirrhosis 1, 3
• A 12-week course resulted in improved total abstinence rates and decreased relapse over 1 year of observation 1

Mechanism:

• GABA-B receptor agonist that reduces craving and relapse risk 1, 3

Safety & Contraindications:

• Acceptable safety profile in cirrhotic patients 1
• Exclude patients with hepatic encephalopathy because baclofen may worsen mentation 1, 3
• Monitor closely for worsening mental status and sedation 1

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Second-Line Medication for Liver Disease

Gabapentin

Dosing:

• 1800 mg/day (600 mg three times daily) 2, 3
• Treat for at least 12 weeks, generally 3-6 months 2

Efficacy:

• NNT = 8 for abstinence and NNT = 5 for non-excessive drinking at 1800 mg/day 2
• Dose-dependent linear effect on complete abstinence: 4.1% (placebo) vs 11.1% (900 mg) vs 17.0% (1800 mg), p=0.04 2

Safety in Liver Disease:

• Not metabolized by the liver; eliminated renally 3
• No hepatotoxicity risk 2
• Safe in severe liver disease 2

Monitoring:

• Monitor renal function and mental status closely 1, 3

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Medications to AVOID in Liver Disease

Disulfiram

• Avoid in severe alcoholic liver disease due to hepatotoxic potential 1, 2, 3
• Not included in current liver disease treatment algorithms 1

Naltrexone (Reiterated)

• Do not prescribe to patients with any elevation of liver enzymes or any hepatic dysfunction from alcohol 3

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Integration With Psychosocial Interventions (Non-Negotiable)

• All pharmacologic regimens must be combined systematically with evidence-based psychosocial therapies 1, 2, 3
• Effective modalities include cognitive-behavioral therapy (CBT), motivational enhancement therapy (MET), motivational interviewing, contingency management, 12-step facilitation, and couples/family counseling 1
• Combined CBT and pharmacotherapy shows benefit over usual care (effect size g=0.18-0.28) 1
• When naltrexone or acamprosate is paired with psychosocial treatment, relapse rates decrease from 54-60% to 23-31% 3

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Expected Clinical Outcomes

• Sustained abstinence improves outcomes across all stages of alcoholic liver disease, lowers portal pressure, and prevents progression to cirrhosis 3
• Naltrexone and acamprosate produce modest effect sizes (≈0.15-0.20) but clinically meaningful reductions in heavy drinking 3
• Baclofen in cirrhotic patients demonstrates higher total-abstinence rates and lower relapse over one year compared with control 3

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Common Pitfalls to Avoid

• Starting naltrexone without verifying 7-10 days opioid-free status and resolution of withdrawal 4
• Prescribing naltrexone to any patient with elevated liver enzymes or alcoholic liver disease 3
• Initiating maintenance medications during active withdrawal instead of benzodiazepines 3
• Failing to administer thiamine before glucose in at-risk patients 2, 3
• Using acamprosate in severe renal impairment without dose adjustment 3
• Prescribing baclofen to patients with hepatic encephalopathy 1, 3
• Omitting psychosocial interventions—pharmacotherapy alone is insufficient 1, 3