What medications are used to treat alcohol use disorder?

Medications for Alcohol Use Disorder

First-Line Pharmacotherapy for Patients Without Liver Disease

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 is FDA-approved and demonstrates efficacy in reducing relapse to heavy drinking with a number needed to treat (NNT) of approximately 20, though it is less effective at maintaining complete abstinence 1, 2

• Naltrexone works by blocking opioid receptors, thereby reducing alcohol's pleasurable effects and decreasing craving 2, 3

• The standard dose is 50 mg once daily, with peak plasma levels occurring within one hour of dosing 2

• Meta-analyses confirm naltrexone has a larger effect size than acamprosate specifically for reducing heavy drinking and craving 4

• Acamprosate is FDA-approved and has an NNT of approximately 12 to prevent return to any drinking 1

• Acamprosate reduces withdrawal effects and craving for alcohol, with desired concentration reached within 1-2 weeks of initiating treatment 5

• The recommended dosage is 1,998 mg/day (666 mg three times daily) for patients ≥60 kg, decreased by one-third for those <60 kg 5, 1

• Treatment should be initiated 3-7 days following the last episode of alcohol consumption, after withdrawal symptoms have resolved 5

• Meta-analyses show acamprosate has a significantly larger effect size than naltrexone on maintenance of abstinence 4

• Treatment duration is typically 3-6 months 5

Critical Contraindication: Patients With Liver Disease

Naltrexone is absolutely contraindicated in patients with alcoholic liver disease due to risk of hepatotoxicity and should never be used in this population. 5, 6, 1

• Naltrexone has not been tested in patients with cirrhosis and its use is not recommended 5
• At the standard 50 mg dose, hepatotoxicity concerns exist, and at higher doses hepatotoxicity is of significant concern 7

First-Line Treatment for Patients With Advanced Liver Disease

For patients with advanced alcoholic liver disease or cirrhosis, baclofen is the preferred and only medication specifically studied and proven safe in this population. 6, 1

• Baclofen is a GABAB receptor agonist that effectively reduces alcohol craving and maintains abstinence 5, 6
• Baclofen is the only alcohol use disorder pharmacotherapy tested in randomized controlled trials in patients with cirrhosis (both compensated and decompensated) 1
• A 12-week course of baclofen in patients with liver cirrhosis effectively maintained abstinence by reducing craving 5
• Baclofen is safe in severe liver disease, unlike naltrexone and disulfiram 6, 1
• The recommended dose is 30-60 mg/day (typically 10 mg three times daily) 1

Second-Line and Off-Label Options

Gabapentin has strong evidence as a second-line treatment, particularly valuable in patients with liver disease:

• The American College of Physicians recommends gabapentin as a second-line treatment for alcohol dependence, particularly in patients with liver disease or when first-line treatments are contraindicated 6
• Gabapentin demonstrates dose-dependent efficacy with optimal results at 1800 mg/day (600 mg three times daily): complete abstinence rates of 4.1% (placebo) vs 11.1% (900 mg) vs 17.0% (1800 mg), p=0.04 6
• The NNT for abstinence is 8 and for non-excessive drinking is 5 at the 1800 mg dose 6
• Gabapentin has no hepatotoxicity risk and is safe in severe liver disease 6, 1
• Treatment duration should be at least 12 weeks, though 3-6 months is generally recommended 6
• Gabapentin improves relapse-related symptoms including insomnia, dysphoria, and craving in a dose-dependent manner 6

Topiramate shows promise but has not been specifically tested in alcoholic liver disease:

• Topiramate has moderate to strong evidence for decreasing heavy-drinking days and may reduce liver enzyme levels 6, 1
• European guidelines identify topiramate as promising for both alcohol withdrawal syndrome and relapse prevention 5, 6
• The tolerance profile requires careful benefit-risk assessment 6

Medications to Avoid

Disulfiram should be avoided in patients with severe alcoholic liver disease:

• Disulfiram is an ALDH inhibitor that causes acetaldehyde buildup following alcohol consumption 5
• It should be avoided in patients with severe alcoholic liver disease due to possible hepatotoxicity 5, 6, 1
• Little evidence supports disulfiram's effectiveness outside of supervised settings 8

Management of Acute Alcohol Withdrawal Syndrome

Benzodiazepines are the gold standard treatment for alcohol withdrawal syndrome, with specific considerations for liver disease. 5, 6, 1

• Benzodiazepines reduce both withdrawal symptoms and the risk of seizures and delirium tremens 5
• For patients with hepatic dysfunction, lorazepam is the preferred benzodiazepine due to its shorter half-life and lack of active metabolites 6, 1
• Short and intermediate-acting benzodiazepines (lorazepam, oxazepam) are safer in elderly patients and those with hepatic dysfunction compared to long-acting ones (diazepam, chlordiazepoxide) 5, 6
• Lorazepam dosing: 1-4 mg PO/IV/IM every 4-8 hours 5
• Benzodiazepines should not be used beyond 10-14 days of treatment due to potential for abuse 6

Essential Nutritional Supplementation

Thiamine supplementation is mandatory to prevent Wernicke encephalopathy:

• Thiamine 100-300 mg/day for 4-12 weeks is crucial for prevention 5, 6, 1
• For management of established Wernicke encephalopathy: 100-500 mg/day for 12-24 weeks 5
• Thiamine must be administered before any glucose-containing IV fluids to prevent precipitating acute thiamine deficiency 5, 6, 1

Treatment Duration and Comprehensive Approach

All pharmacological treatments must be combined with psychosocial interventions for optimal outcomes:

• Alcohol abstinence is the most important treatment for alcoholic liver disease, as it improves survival and prevents progression to cirrhosis 5, 6, 1
• Pharmacotherapy should always be combined with psychosocial interventions such as cognitive-behavioral therapy, motivational interviewing, and structured counseling 6, 1
• The combination of pharmacotherapy and psychotherapy demonstrates superior efficacy compared to usual care alone 6
• Regular monitoring of liver function tests is essential to assess improvement and medication effects 6, 1
• Treatment duration for maintenance medications is typically 3-6 months, though many clinicians recommend one year of treatment 5, 7

Clinical Algorithm Summary

For patients WITHOUT advanced liver disease:

1. Start naltrexone 50 mg daily OR acamprosate 666 mg three times daily 1
2. If contraindicated or ineffective, use gabapentin 1800 mg/day (600 mg three times daily) 6
3. Consider topiramate as an alternative 1

For patients WITH advanced liver disease or cirrhosis:

1. Start baclofen 30-60 mg/day (10 mg three times daily) 6, 1
2. If contraindicated or ineffective, use gabapentin 1800 mg/day 6
3. Never use naltrexone or disulfiram 6, 1

For acute alcohol withdrawal:

1. Use lorazepam (preferred in liver disease) 1-4 mg every 4-8 hours 5, 6, 1
2. Administer thiamine 100-300 mg/day BEFORE any glucose-containing IV fluids 5, 6, 1
3. Limit benzodiazepine use to 10-14 days maximum 6