What medications are used to treat alcoholism?

Medications for Alcohol Use Disorder

For patients with normal liver function, naltrexone 50 mg daily or acamprosate 666 mg three times daily are the first-line FDA-approved medications, while baclofen 30-60 mg daily is the preferred choice for patients with alcoholic liver disease. 1, 2

FDA-Approved Medications

Naltrexone (First-Line for Normal Liver Function)

• Naltrexone 50 mg once daily is FDA-approved and reduces the risk of relapse to heavy drinking and decreases drinking frequency, though it does not substantially enhance complete abstinence. 1, 3
• The number needed to treat to prevent return to any drinking is approximately 20. 1
• Naltrexone is also available as a monthly injectable formulation (380 mg subcutaneously). 1
• Critical contraindication: Naltrexone must be avoided in patients with alcoholic liver disease due to hepatotoxicity risk and should not be used in those with elevated liver enzymes. 1, 2, 4
• Patients must be opioid-free for a minimum of 7-10 days before starting naltrexone to avoid precipitated withdrawal. 3

Acamprosate (First-Line for Normal Liver Function)

• Acamprosate 666 mg three times daily (1,998 mg/day total) is FDA-approved and reduces drinking frequency with a number needed to treat of approximately 12. 1, 2
• Acamprosate has no hepatic metabolism and no reported instances of hepatotoxicity, making it safe in liver disease. 1, 2
• The medication works as an NMDA receptor antagonist and is renally excreted. 1

Disulfiram (Limited Role)

• Disulfiram is FDA-approved but should not be used in patients with severe alcoholic liver disease due to possible hepatotoxicity. 1, 2, 4
• Evidence for disulfiram shows mixed outcomes with some reduction in drinking frequency but minimal evidence for improved continuous abstinence rates. 1

Preferred Medication for Alcoholic Liver Disease

Baclofen (First-Line for Liver Disease)

• Baclofen 30-60 mg daily (up to 80 mg/day maximum) is the only medication specifically studied and proven safe in patients with alcoholic liver disease and cirrhosis. 1, 2, 4
• A randomized trial in patients with both compensated and decompensated cirrhosis demonstrated that baclofen 10 mg three times daily for 12 weeks resulted in improved rates of total alcohol abstinence and decreased relapse over 1 year. 1
• Important caveat: Patients with hepatic encephalopathy should be excluded from baclofen treatment as it may impair mentation. 1
• Baclofen is a GABA-B receptor agonist with hepatic metabolism but has been proven safe in the cirrhotic population. 1, 2

Off-Label Medications with Promising Evidence

Gabapentin

• Gabapentin 600-1,800 mg daily has shown effectiveness in treating alcohol use disorder and offers distinct advantages in liver disease with no hepatotoxicity risk. 1, 2
• The medication has no hepatic metabolism and is renally excreted (75% renal, 25% fecal). 1
• Monitor closely for renal dysfunction and worsening mental status/sedation. 1

Topiramate

• Topiramate 75-400 mg daily has demonstrated efficacy in reducing heavy drinking and may decrease liver enzyme levels. 1, 2, 5
• The medication works through GABA action augmentation and glutamate antagonism but has not been specifically tested in patients with alcoholic liver disease. 1, 2

Clinical Algorithm for Medication Selection

Step 1: Assess liver function

• If normal liver enzymes and no liver disease → Consider naltrexone 50 mg daily OR acamprosate 666 mg three times daily 1, 3
• If elevated liver enzymes or alcoholic liver disease → Use baclofen 30-60 mg daily (up to 80 mg/day) 1, 2, 4

Step 2: Screen for contraindications

• Check for current opioid use (naltrexone contraindicated) 3
• Assess for hepatic encephalopathy (baclofen contraindicated) 1
• Evaluate renal function (acamprosate and gabapentin require dose adjustment) 1

Step 3: Consider second-line options if first-line fails or is not tolerated

• Gabapentin 600-1,800 mg daily (safe in liver disease) 1, 2
• Topiramate 75-400 mg daily (not studied in liver disease but promising) 1, 2, 5

Essential Supportive Care

• Thiamine 100-300 mg daily for 4-12 weeks must be administered to all patients to prevent Wernicke encephalopathy, and must be given before any glucose-containing IV fluids. 2, 4, 5
• For acute alcohol withdrawal, benzodiazepines are first-line treatment, with lorazepam preferred in liver dysfunction due to shorter half-life and lack of active metabolites. 2, 4
• Benzodiazepines should not be continued beyond 10-14 days due to abuse potential. 2, 5

Critical Monitoring

• Regular liver function tests should be performed to assess improvement and monitor for medication effects. 2, 5
• Alcohol abstinence remains the most important intervention for improving survival and preventing progression to cirrhosis, and pharmacotherapy should be combined with psychosocial interventions. 2
• Medication compliance is crucial for success, and compliance-enhancing techniques should be implemented. 3