What medications are used to treat alcohol use disorder?

Medications for Alcohol Use Disorder

First-Line Pharmacotherapy

For patients without advanced liver disease, naltrexone (50 mg daily) or acamprosate (666 mg three times daily) combined with counseling are the primary evidence-based medications to reduce alcohol consumption and prevent relapse. 1

Naltrexone

• Reduces relapse to heavy drinking with a number needed to treat of approximately 20, though it is less effective at maintaining complete abstinence 1
• Works as an opioid receptor antagonist to block alcohol's rewarding effects and reduce craving 2, 3
• Demonstrates consistent small to moderate effects in reducing frequency of drinking and heavy drinking days 4
• Contraindicated in patients with advanced alcoholic liver disease due to hepatotoxicity risk and hepatic metabolism 1, 5
• Available as 50 mg daily oral formulation or 380 mg monthly intramuscular injection 1
• Requires patients to be opioid-free for minimum 7-10 days before initiation; up to 2 weeks for those transitioning from buprenorphine or methadone 3

Acamprosate

• Number needed to treat of approximately 12 to prevent return to any drinking 1
• Functions as an NMDA receptor antagonist, similar to GABA, reducing withdrawal symptoms and craving 2
• Safe in advanced liver disease as it undergoes no hepatic metabolism and is renally excreted 1, 5
• More effective at maintaining abstinence rather than inducing it 2
• Dosing: 666 mg three times daily for patients ≥60 kg 5

Special Population: Advanced Alcoholic Liver Disease

Baclofen is the preferred and only medication specifically studied in patients with advanced alcoholic liver disease, including cirrhosis. 1, 5

Baclofen

• The only AUD pharmacotherapy tested in randomized controlled trial in patients with cirrhosis (both compensated and decompensated) 1
• GABA-B receptor agonist that promotes alcohol abstinence and reduces craving 5, 2
• Standard dosing: 10 mg three times daily (30 mg/day total), with range of 30-60 mg/day 1, 2
• Safe in severe liver disease unlike naltrexone and disulfiram 5
• Recommended treatment duration of several months 5

Second-Line and Off-Label Options

Gabapentin

• Strong evidence for reducing heavy-drinking days 6
• Dosing range: 600-1,800 mg/day, renally excreted with no hepatic metabolism 1
• Advantages in liver disease: no hepatotoxicity risk, safe in severe hepatic dysfunction 5
• Modulates GABA activity but requires careful monitoring for renal dysfunction and mental status changes 1

Topiramate

• Moderate to strong evidence for decreasing heavy-drinking days and may reduce liver enzyme levels 5, 4, 6
• Dosing: 75-400 mg/day 1
• Mechanism: augments GABA action and antagonizes glutamate 1
• Not specifically studied in patients with alcoholic liver disease 1

Disulfiram

• Creates aversive reaction through aldehyde dehydrogenase inhibition causing acetaldehyde accumulation 2
• Should be avoided in severe alcoholic liver disease due to hepatotoxicity risk 5
• Little evidence supports effectiveness outside supervised settings 6
• Not recommended as first-line therapy 1

Management of Acute Alcohol Withdrawal

Benzodiazepines are the gold standard treatment for alcohol withdrawal syndrome. 1, 2

Benzodiazepine Selection

• Lorazepam is preferred in patients with liver dysfunction due to shorter half-life and lack of active metabolites 5
• Short and intermediate-acting agents (lorazepam, oxazepam) are safer than long-acting ones (diazepam, chlordiazepoxide) in hepatic dysfunction 5, 2
• Symptom-triggered regimen using CIWA-Ar scale recommended to prevent accumulation 2
• Should not be used beyond 10-14 days due to abuse potential 5

Essential Nutritional Support

• Thiamine 100-300 mg/day for 4-12 weeks is crucial to prevent Wernicke encephalopathy 5
• Must be administered before any glucose-containing IV fluids to prevent precipitating acute thiamine deficiency 5

Critical Clinical Algorithm

For Patients WITHOUT Advanced Liver Disease:

1. First choice: Naltrexone 50 mg daily OR Acamprosate 666 mg three times daily 1
2. Second choice: Gabapentin 600-1,800 mg/day or Topiramate 75-400 mg/day 1, 6
3. Always combine with psychosocial interventions and counseling 1, 2

For Patients WITH Advanced Liver Disease or Cirrhosis:

1. First and only proven choice: Baclofen 30-60 mg/day (10 mg three times daily) 1, 5
2. Alternative: Acamprosate 666 mg three times daily (safe due to renal excretion) 1, 5
3. Consider: Gabapentin 600-1,800 mg/day (no hepatotoxicity) 5
4. Avoid: Naltrexone and disulfiram (hepatotoxicity risk) 1, 5

Common Pitfalls to Avoid

• Never use naltrexone in patients with elevated liver enzymes or advanced liver disease due to hepatotoxicity concerns 1, 5
• Do not initiate naltrexone without ensuring 7-10 day opioid-free period to avoid precipitated withdrawal 3
• Avoid disulfiram in any patient with significant liver disease 5
• Do not forget thiamine supplementation before glucose administration in withdrawal management 5
• Monitor for medication compliance as this is the primary limitation of pharmacotherapy effectiveness 1, 7

Treatment Duration and Monitoring

• Most clinical trials studied 12-week treatment periods, though many clinicians recommend one year of treatment 8
• Alcohol abstinence remains the most important therapeutic intervention and improves survival while preventing progression to cirrhosis 5, 2
• Regular monitoring of liver function tests is essential to assess improvement and medication effects 5
• All pharmacological treatments must be combined with psychosocial support for optimal outcomes 1, 2