What medications are used to treat alcohol use disorder (AUD)?

Medications for Alcohol Use Disorder

For alcohol use disorder, start with naltrexone 50 mg daily or acamprosate 1,998 mg daily as first-line pharmacotherapy, combined with psychosocial interventions, as these are the FDA-approved medications with the strongest evidence for reducing alcohol consumption and maintaining abstinence. 1, 2

FDA-Approved First-Line Medications

The four FDA-approved medications for AUD are disulfiram, oral naltrexone, extended-release injectable naltrexone, and acamprosate 3. However, their efficacy profiles differ substantially:

Naltrexone (Preferred for Most Patients)

• Naltrexone 50 mg once daily is the first choice for patients without liver disease, as it blocks opioid receptors and dampens the dopamine reward pathway, reducing excessive drinking and increasing abstinence duration 1, 2, 4.
• Extended-release injectable naltrexone was specifically FDA-approved for increasing the proportion of subjects with no heavy drinking days 3.
• In clinical trials, naltrexone demonstrated lower relapse rates (21% vs 41% placebo) and fewer drinking days 4.
• Critical contraindication: Do NOT use naltrexone in patients with severe liver disease due to hepatotoxicity risk 2.

Acamprosate (Preferred for Liver Disease)

• Acamprosate 1,998 mg daily is the first choice for patients with liver disease or those already abstinent, as it modulates glutamate receptors to reduce withdrawal symptoms and craving without hepatotoxicity 1, 2.
• Network meta-analysis showed acamprosate increased odds of abstinence (OR 1.86,95% CI 1.49-2.33) and reduced dropout rates (OR 0.73,95% CI 0.62-0.86) 3.
• Acamprosate was approved by FDA for increasing abstinence more than placebo 3.

Disulfiram (Limited Role)

• Disulfiram creates an aversive reaction when alcohol is consumed but has inconsistent evidence for effectiveness 3, 5.
• Network meta-analysis found disulfiram was NOT associated with improved abstinence (OR 0.93,95% CI 0.48-1.79) 3.
• Should only be used in supervised settings where compliance can be monitored, and avoided in severe liver disease 3, 2.

Clinical Decision Algorithm

For patients WITHOUT liver disease:

1. Start naltrexone 50 mg daily 1, 2
2. Alternative: acamprosate 1,998 mg daily 1, 2

For patients WITH liver disease:

1. Start acamprosate 1,998 mg daily 2
2. Alternative: baclofen (up to 80 mg daily) 2

Combination Therapy (Superior Efficacy)

Network meta-analysis identified four combination interventions more effective than placebo:

• Acamprosate + naltrexone (OR 3.68,95% CI 1.50-9.02) 3
• Acamprosate + nurse visits (OR 4.59,95% CI 1.47-14.36) 3
• Sodium oxybate + naltrexone (OR 12.64,95% CI 2.77-57.78) 3
• Naltrexone + sodium oxybate + escitalopram (OR 25.65,95% CI 2.13-309.46) 3

Off-Label Medications with Evidence

Topiramate (Strong Evidence)

• Network meta-analysis showed topiramate increased abstinence (OR 1.88,95% CI 1.06-3.34) and reduced dropouts (OR 0.45,95% CI 0.24-0.83) 3.
• May reduce heavy drinking and decrease liver enzyme levels 2.

Baclofen (For Advanced Liver Disease)

• GABAB receptor agonist shown to promote abstinence in alcoholic cirrhotic patients 2.
• One randomized trial in cirrhosis patients suggested benefit in achieving and maintaining abstinence 3.

Gabapentin

• May reduce alcohol ingestion, though long-term studies are lacking 5.
• Considered for off-label use 6, 7.

Essential Treatment Components

All pharmacotherapy MUST be combined with psychosocial interventions 1, 2:

• Cognitive behavioral therapy (CBT) shows superior efficacy when combined with medication 2.
• Brief motivational interventions should be routinely used 2.
• Medication alone is insufficient 2.

Management of Acute Alcohol Withdrawal

Before starting AUD medications, manage withdrawal if present:

• Benzodiazepines are the gold standard for alcohol withdrawal syndrome 3, 2.
• Administer thiamine 100-300 mg daily for 4-12 weeks BEFORE any glucose-containing IV fluids to prevent Wernicke's encephalopathy 2.
• All patients should receive oral thiamine; high-risk patients (malnourished, severe withdrawal) require parenteral thiamine 3.

Critical Pitfalls to Avoid

1. Never prescribe naltrexone to patients with severe liver disease 2
2. Never use disulfiram in advanced liver disease 2
3. Never prescribe medication without psychosocial interventions 2
4. Never start naltrexone without ensuring 7-10 days opioid-free (including tramadol) 4
5. Never discontinue medication too early—treat for 3-6 months minimum 2
6. Never give glucose before thiamine in at-risk patients 2

Treatment Duration and Monitoring

• FDA trials used naltrexone 50 mg once daily for 12 weeks 4.
• Treatment duration of 3-6 months is typically recommended 2.
• Screen for alcohol use with validated tools like AUDIT before initiating treatment 2.
• Monitor for psychiatric comorbidities that may affect outcomes 2.