Is Medication-Assisted Treatment (MAT) applicable for alcohol use disorder?

Medication-Assisted Treatment for Alcohol Use Disorder

Yes, Medication-Assisted Treatment (MAT) is absolutely applicable and evidence-based for alcohol use disorder, with naltrexone, acamprosate, and gabapentin representing first-line pharmacotherapies that should be combined with psychosocial interventions. 1

FDA-Approved Medications for Alcohol Use Disorder

The three FDA-approved medications for treating AUD are naltrexone (oral and long-acting injectable), acamprosate, and disulfiram, though disulfiram is not recommended for patients with alcohol-associated liver disease. 1, 2

Naltrexone (First-Line Option)

• Naltrexone reduces the likelihood of return to any drinking by 5% and binge-drinking risk by 10%, making it a first-line treatment for moderate to severe AUD. 3
• The oral formulation is dosed at 50 mg daily, while the extended-release injectable (Vivitrol) is given as 380 mg monthly. 1, 4, 2
• Naltrexone works as an opioid receptor antagonist, blocking the euphoric effects and dampening activation of the reward pathway by alcohol. 4, 2
• Critical caveat: Naltrexone undergoes hepatic metabolism and carries hepatotoxicity concerns, particularly at supratherapeutic doses, requiring baseline and every 3-6 months liver function monitoring. 1, 4, 2
• Naltrexone has not been studied specifically in patients with alcohol-associated liver disease, and should be avoided in decompensated cirrhosis or acute hepatitis. 1

Acamprosate (First-Line for Abstinence Maintenance)

• Acamprosate is dosed at 666 mg three times daily and works as an NMDA receptor antagonist. 1
• Acamprosate has no hepatic metabolism and no reported instances of hepatotoxicity, making it the safest option for patients with liver disease. 1
• The number needed to treat to prevent return to any drinking is approximately 12 for acamprosate. 1
• Acamprosate is primarily renally excreted and should be dose-adjusted in renal impairment. 1

Disulfiram (Limited Role)

• Disulfiram is not recommended for patients with alcohol-associated liver disease due to hepatotoxicity concerns. 1
• Little evidence supports disulfiram's effectiveness outside of supervised settings. 5

Off-Label Medications with Strong Evidence

Gabapentin (Recommended Off-Label)

• Strong evidence shows gabapentin at doses of 600-1,800 mg/day reduces heavy-drinking days. 5
• Gabapentin has no hepatic metabolism (75% renal, 25% fecal excretion) and modulates GABA activity. 1
• Monitor closely for renal dysfunction and worsening mental status/sedation. 1

Topiramate (Recommended Off-Label)

• Moderate evidence supports topiramate at 75-400 mg/day in decreasing heavy-drinking days. 5, 6
• Topiramate augments GABA action and antagonizes glutamate, with minimal hepatic metabolism. 1
• Topiramate demonstrates consistent small to moderate effects in reducing drinking frequency. 6

Baclofen (Limited Evidence in Liver Disease)

• Baclofen (30-60 mg/day) is a GABA-B receptor agonist and the only AUD pharmacotherapy tested in a randomized controlled trial specifically in patients with cirrhosis. 1
• In patients with compensated and decompensated cirrhosis, 12 weeks of baclofen (10 mg three times daily) improved total alcohol abstinence rates compared to control during 1 year of observation. 1
• Critical caveat: Patients with hepatic encephalopathy were excluded from baclofen trials, as it may impair mentation. 1

Integration with Psychosocial Treatment

• Medications for AUD are only effective when combined with comprehensive psychosocial treatment, including cognitive-behavioral therapy, motivational interviewing, motivational enhancement therapy, and mutual aid societies. 1, 3
• Integrating AUD treatment with medical care remains the best option for management of advanced alcohol-associated liver disease and AUD. 1
• Five randomized controlled trials in patients with alcohol-associated liver disease showed that integrated interventions combining AUD treatment with medical care produced the best outcomes. 1

Treatment Algorithm for Medication Selection

For patients WITHOUT liver disease:

• Start with naltrexone 50 mg daily (oral) or 380 mg monthly (injectable) as first-line, combined with psychosocial interventions. 3, 5
• Alternative first-line: Acamprosate 666 mg three times daily for patients prioritizing abstinence maintenance. 1, 5
• Second-line off-label: Gabapentin 600-1,800 mg/day or topiramate 75-400 mg/day. 5, 6

For patients WITH compensated liver disease:

• Acamprosate is the safest first-line choice due to no hepatic metabolism and no hepatotoxicity. 1
• Baclofen 30-60 mg/day is an alternative with specific evidence in cirrhosis. 1
• Naltrexone requires case-by-case assessment with close liver function monitoring. 1

For patients WITH decompensated cirrhosis:

• Naltrexone is contraindicated; use acamprosate or baclofen instead. 1
• Avoid disulfiram completely in any alcohol-associated liver disease. 1

Common Pitfalls to Avoid

• Do not delay pharmacotherapy while waiting for psychosocial interventions to begin—medications should be started immediately upon AUD diagnosis. 3, 7
• Do not use disulfiram in patients with any degree of liver disease. 1
• Do not prescribe naltrexone without baseline liver function tests and ongoing monitoring every 3-6 months. 4, 2
• Do not fail to recognize that less than 9% of patients who could benefit from AUD medications actually receive them, representing a massive treatment gap. 3, 8
• Do not use naltrexone in patients requiring opioids for pain control, as it blocks opioid analgesia. 4
• Do not prescribe baclofen to patients with hepatic encephalopathy due to risk of worsening mental status. 1

Underutilization Crisis

• Despite being first-line treatments in clinical practice guidelines, AUD medications are prescribed to less than 9% of patients who would benefit from them. 3, 8
• Only 7.3% of Americans with AUD received any treatment in 2019, and only 1.6% were prescribed medications. 5
• This represents a critical failure in translating evidence into practice, as pharmacotherapy combined with behavioral interventions significantly improves outcomes compared to behavioral interventions alone. 3, 7