What are the evidence-based medications for alcohol use disorder?

Evidence-Based Medications for Alcohol Use Disorder

For alcohol use disorder, offer naltrexone, acamprosate, or disulfiram as first-line pharmacotherapy combined with psychosocial interventions, with medication selection based on patient-specific factors including liver function, craving intensity, and treatment goals. 1, 2

First-Line Medication Options

Naltrexone (Preferred for Most Patients)

• Naltrexone 50 mg daily is the most effective first-line option for patients with high alcohol cravings and no liver disease, demonstrating superior efficacy in reducing heavy drinking days and preventing relapse (abstention rates 51% vs 23% placebo, relapse rates 31% vs 60% placebo). 3
• Naltrexone works by blocking opioid receptors, reducing the pleasurable "high" associated with drinking and decreasing alcohol craving. 2
• Contraindicated in patients with severe liver disease due to hepatotoxicity risk—this is a critical safety consideration that eliminates naltrexone as an option for patients with elevated liver enzymes or cirrhosis. 4, 2
• Patients must be opioid-free for 7-10 days before starting naltrexone to avoid precipitated withdrawal. 3
• Most common side effect is nausea; hepatotoxicity at standard 50 mg dose is not a clinical concern. 5
• Naltrexone is particularly effective in patients with high baseline craving levels or strong family history of alcoholism. 6

Acamprosate (Preferred for Maintaining Abstinence)

• Acamprosate 1,998 mg daily (666 mg three times daily) is the preferred option for patients already abstinent or with liver disease, as it modulates glutamate receptors to reduce withdrawal symptoms and craving without hepatotoxicity risk. 1, 2
• Demonstrates moderate evidence for maintaining abstinence up to 12 months. 2
• Safe in patients with liver dysfunction, making it the first choice when naltrexone is contraindicated. 4, 2
• Renally cleared, requiring dose adjustment in renal impairment. 1

Disulfiram (For Supervised Settings)

• Disulfiram creates an aversive reaction when alcohol is consumed but should only be used in supervised settings where medication compliance can be monitored, as evidence for effectiveness outside supervised contexts is limited. 1, 7
• Avoid in patients with severe alcoholic liver disease due to potential hepatotoxicity. 4, 2
• Requires highly motivated patients with external accountability structures. 1

Second-Line and Alternative Medications

Baclofen (Preferred for Patients with Liver Disease)

• Baclofen is the preferred medication for patients with alcoholic liver disease or cirrhosis, as it demonstrates safety and efficacy in promoting abstinence in this population where naltrexone is contraindicated. 4, 2
• Dosing up to 80 mg daily, typically divided into multiple doses throughout the day. 2
• Acts as a GABAB receptor agonist to reduce alcohol craving. 2
• Treatment should continue for several months to maintain abstinence. 4

Gabapentin (Emerging Evidence)

• Gabapentin shows promise for patients who cannot tolerate FDA-approved medications, particularly those with liver disease, as it carries no hepatotoxicity risk. 4, 7
• Strong evidence demonstrates reduction in heavy-drinking days. 7
• Safe in severe liver disease, offering an advantage over naltrexone and disulfiram. 4

Topiramate (Off-Label, Effective for Heavy Drinking)

• Topiramate demonstrates consistent moderate effects in decreasing heavy-drinking days and may reduce liver enzyme levels. 4, 2, 8
• Not FDA-approved for AUD but supported by moderate-quality evidence. 7
• Requires careful benefit-risk assessment due to tolerability concerns including cognitive side effects. 4

Critical Treatment Algorithm

Step 1: Assess Liver Function

• If normal liver function and high craving: Start naltrexone 50 mg daily 2, 3
• If elevated liver enzymes or cirrhosis: Choose acamprosate 1,998 mg daily OR baclofen up to 80 mg daily 4, 2
• If severe liver disease: Baclofen is preferred; avoid naltrexone and disulfiram 4, 2

Step 2: Verify Opioid-Free Status (If Using Naltrexone)

• Patients must be opioid-free (including tramadol) for minimum 7-10 days before starting naltrexone. 3
• Consider naloxone challenge test if occult opioid dependence is suspected. 3
• Patients switching from buprenorphine or methadone may require up to 2 weeks opioid-free. 3

Step 3: Combine with Psychosocial Interventions

• All pharmacotherapy must be combined with psychosocial interventions such as cognitive behavioral therapy, motivational enhancement, or contingency management—medication alone is insufficient. 1, 2
• Combined CBT and pharmacotherapy shows superior efficacy (effect size 0.18-0.28) compared to usual care alone. 1
• Brief motivational interventions (5-30 minutes) should be routinely incorporated. 1, 2

Step 4: Treatment Duration and Monitoring

• Treat for minimum 3-6 months; many clinicians recommend 12 months of continuous treatment. 2, 3
• Monitor liver function tests regularly when using any medication. 4
• Screen for psychiatric comorbidities that may affect treatment outcomes. 2

Management of Acute Alcohol Withdrawal (Separate from Relapse Prevention)

Benzodiazepines are the gold standard for alcohol withdrawal syndrome, with lorazepam preferred in patients with liver dysfunction due to shorter half-life and lack of active metabolites. 1, 4

• Short-acting benzodiazepines (lorazepam) are safer than long-acting ones (diazepam, chlordiazepoxide) in hepatic dysfunction. 4
• Limit benzodiazepine use to 10-14 days maximum to prevent abuse potential. 4
• All patients should receive thiamine 100-300 mg daily for 4-12 weeks to prevent Wernicke encephalopathy. 1, 4
• Administer thiamine before any glucose-containing IV fluids. 4

Common Pitfalls to Avoid

• Never prescribe naltrexone to patients with severe liver disease or active hepatitis—this is the most critical safety error. 4, 2
• Never start naltrexone without confirming adequate opioid-free period—risk of severe precipitated withdrawal. 3
• Never use disulfiram in patients with advanced liver disease. 4, 2
• Never prescribe medication without concurrent psychosocial intervention—pharmacotherapy alone has limited efficacy. 1, 2
• Never discontinue medication prematurely—minimum 3-6 months treatment duration is required. 2
• Never use benzodiazepines beyond 10-14 days—abuse potential increases significantly. 4
• Never give glucose before thiamine in at-risk patients—may precipitate acute Wernicke encephalopathy. 4

Special Populations

Patients with Comorbid Depression

• Antidepressants do not decrease alcohol use in patients without mood disorders. 7
• In patients meeting criteria for depression, treating the mood disorder may help decrease alcohol intake. 7

Patients Requiring Supervised Administration

• Consider alternative dosing schedules: 50 mg weekdays with 100 mg Saturday, 100 mg every other day, or 150 mg every third day for supervised settings. 3
• Disulfiram is most effective when administration is directly observed. 1, 7