What medications are appropriate for the management of Alcohol Use Disorder (AUD)?

Medications for Alcohol Use Disorder

For most patients with alcohol use disorder, naltrexone 50 mg daily or acamprosate 1,998 mg daily should be prescribed as first-line pharmacotherapy, combined with psychosocial interventions. 1, 2, 3

First-Line Pharmacotherapy Options

Naltrexone and acamprosate are FDA-approved, guideline-recommended first-line medications with Grade A evidence for efficacy. 4, 1, 5

Naltrexone

• Reduces risk of return to any drinking by 5% and binge-drinking risk by 10% 5
• Blocks opioid receptors, reducing the pleasurable effects and cravings associated with alcohol 1
• Dose: 50 mg once daily 3, 5
• Contraindicated in patients with severe liver disease due to hepatotoxicity risk 6, 1
• Requires 7-10 day opioid-free period before initiation 3

Acamprosate

• Modulates glutamate receptors to reduce withdrawal symptoms and cravings 1
• Safe in patients with liver disease, making it preferred when hepatic dysfunction is present 6, 1
• Dose: 1,998 mg daily (for patients ≥60 kg) 6, 2
• Moderate evidence for maintaining abstinence up to 12 months 1
• Must be initiated after patient achieves abstinence 2

Disulfiram

• Creates aversive reaction when alcohol is consumed 4
• Mixed evidence (Grade B) - some studies show reduced drinking frequency but minimal impact on continuous abstinence 7
• Contraindicated in severe alcoholic liver disease due to hepatotoxicity risk 6, 1
• Most effective when administration is supervised 7

Special Population: Patients with Liver Disease

For patients with elevated liver enzymes or alcoholic liver disease, use this algorithm: 6, 1

First Choice: Baclofen

• Baclofen is the preferred medication for patients with alcoholic liver disease or cirrhosis 6, 1
• GABA-B receptor agonist that reduces cravings and maintains abstinence 6, 1
• Safe in advanced liver disease, including cirrhosis 6, 1
• Dose: Up to 80 mg daily, continued for several months 6
• Caution: May accumulate and cause neonatal withdrawal syndrome in pregnancy 4

Second Choice: Acamprosate

• No hepatotoxicity risk 6
• Dose: 1,998 mg daily 6

Third Choice: Gabapentin (Off-Label)

• No hepatotoxicity risk 6
• Safe in severe liver disease 6
• Particularly useful for patients with concurrent alcohol withdrawal symptoms 8

Avoid in Liver Disease:

• Naltrexone - hepatotoxic 6, 1
• Disulfiram - hepatotoxic 6, 1

Acute Alcohol Withdrawal Management

Benzodiazepines are the gold standard for alcohol withdrawal syndrome. 4, 6

• Lorazepam is preferred in patients with liver dysfunction due to shorter half-life and no active metabolites 6
• Benzodiazepines prevent and treat seizures and delirium 4
• Limit use to 10-14 days maximum to prevent abuse 6
• Thiamine 100-300 mg/day must be given before any glucose-containing IV fluids to prevent Wernicke encephalopathy 6
• Antipsychotics should only be used as adjunct to benzodiazepines in severe delirium unresponsive to adequate benzodiazepine doses 4

Off-Label Medications with Emerging Evidence

Topiramate

• Anticonvulsant showing efficacy in reducing heavy drinking 1, 8
• May decrease liver enzyme levels 6, 1
• Not specifically tested in alcoholic liver disease 6

Gabapentin

• Effective for alcohol withdrawal symptoms 8
• Overall disappointing results except in withdrawal context 8

Varenicline

• Benefits individuals with less severe AUD or concurrent nicotine use 8

Essential Treatment Principles

All pharmacotherapy must be combined with psychosocial interventions for optimal outcomes. 4, 1

• Cognitive behavioral therapy (CBT) plus pharmacotherapy is superior to usual care plus pharmacotherapy 4
• CBT performs equivalently to other evidence-based therapies (motivational enhancement, contingency management) when combined with medication 4
• Brief motivational interventions should be routinely used 1
• Treatment duration of 3-6 months is typically recommended 1

Critical Pitfalls to Avoid

• Never prescribe naltrexone to patients with severe liver disease 6, 1
• Never use disulfiram in advanced liver disease 6, 1
• Never give glucose before thiamine in withdrawal management 6
• Never use benzodiazepines beyond 10-14 days 6
• Never use antipsychotics as monotherapy for alcohol withdrawal 4
• Never prescribe medication without concurrent psychosocial support 1, 2
• Never discontinue medication prematurely - minimum 3-6 months needed 1