What medications are used to treat alcohol abuse?

Medications for Alcohol Abuse Treatment

For patients without advanced liver disease, naltrexone (50 mg daily) or acamprosate (666 mg three times daily) combined with counseling are first-line pharmacological treatments to maintain abstinence, while baclofen (30-60 mg daily) is the only medication proven safe and effective specifically for patients with cirrhosis or advanced alcoholic liver disease. 1, 2

First-Line Medications by Clinical Context

For Patients WITHOUT Advanced Liver Disease

Naltrexone is highly effective as an opioid receptor antagonist that controls alcohol craving and reduces relapse risk 1, 2:

• Standard dosing: 50 mg once daily 3
• Number needed to treat to prevent return to drinking: approximately 20 1
• Increases time to first relapse and reduces drinking days 4
• Critical contraindication: Cannot be used in patients with hepatic dysfunction due to hepatotoxicity risk 1
• Must ensure patients are opioid-free for 7-10 days before initiation to avoid precipitated withdrawal 3
• Most effective when combined with cognitive behavioral therapy (CBT) rather than less intensive counseling 4

Acamprosate works as an NMDA receptor antagonist with GABA-like properties to reduce withdrawal symptoms and craving 1, 2:

• Dosing: 666 mg three times daily 1
• Number needed to treat: approximately 12 1
• Key advantage: No hepatic metabolism, making it safe in liver disease 1
• More effective at maintaining rather than inducing remission 1
• Must be used in combination with counseling and support 1
• Not studied extensively in patients with cirrhosis, but appears safe based on its metabolic profile 1

For Patients WITH Advanced Liver Disease or Cirrhosis

Baclofen is the ONLY medication with proven safety and efficacy in patients with alcoholic cirrhosis 1, 2:

• Dosing: 10 mg three times daily (30 mg/day total), can increase to 60 mg/day 1, 2
• Mechanism: GABA-B receptor agonist that reduces alcohol craving 1, 2
• In a randomized trial of patients with compensated and decompensated cirrhosis, 12 weeks of baclofen resulted in improved total abstinence rates and decreased relapse compared to placebo over 1 year 1
• Important caveat: Patients with hepatic encephalopathy were excluded from trials, as baclofen may impair mentation 1
• More gradual dose titration recommended in severe liver disease 1

Medications to AVOID in Advanced Liver Disease

Disulfiram should be avoided entirely in patients with severe alcoholic liver disease 1:

• Causes hepatotoxicity and can precipitate hepatic failure 1, 5
• Works by inhibiting aldehyde dehydrogenase, creating aversive reaction with alcohol 2
• May be effective in patients without liver disease but carries unacceptable risk in ALD 1

Naltrexone is contraindicated in advanced liver disease 1:

• Undergoes hepatic metabolism and causes hepatocellular injury 1
• Has not been tested in patients with cirrhosis 1
• The 2022 French guidelines note the contraindication is not supported by solid data, but recommend case-by-case assessment only in exceptional circumstances 1

Second-Line and Investigational Options

Gabapentin (600-1,800 mg/day) modulates GABA activity and shows promise 1:

• Not studied in patients with ALD 1
• Requires close monitoring for renal dysfunction and worsening mental status/sedation 1

Topiramate (75-400 mg/day) augments GABA action and antagonizes glutamate 1:

• Demonstrated safety and efficacy in reducing heavy drinking 1
• Decreased liver enzyme levels in treated patients 1
• Not yet tested in patients with ALD 1

Management of Alcohol Withdrawal Syndrome

Benzodiazepines are the gold standard for alcohol withdrawal syndrome, reducing both withdrawal symptoms and risk of seizures/delirium tremens 1:

For patients WITHOUT hepatic dysfunction:

• Long-acting benzodiazepines (diazepam, chlordiazepoxide) provide better protection against seizures and delirium 1
• Chlordiazepoxide: 25-100 mg every 4-6 hours 1
• Diazepam: 5-10 mg every 6-8 hours 1

For patients WITH hepatic dysfunction, elderly, or at risk for encephalopathy:

• Short/intermediate-acting benzodiazepines are safer: lorazepam or oxazepam 1
• Lorazepam: 1-4 mg every 4-8 hours 1
• This precaution aims to avoid drug accumulation, though the superiority of short-acting agents in hepatic insufficiency has not been validated by controlled trials 1

Thiamine supplementation is mandatory to prevent Wernicke's encephalopathy 1, 2:

• Dosing: 100-300 mg/day for prevention, continued for 2-3 months 1
• For treatment of Wernicke's: 100-500 mg/day for 12-24 weeks 1
• Must be given BEFORE IV glucose administration to prevent precipitating acute thiamine deficiency 1

Critical Treatment Principles

Abstinence is the cornerstone of therapy and must be the primary goal 1, 2:

• Continued alcohol use is associated with disease progression at all stages of ALD 1
• After an episode of alcoholic hepatitis, there is no safe amount of alcohol consumption 1
• Risk of cirrhosis is clearly higher in those who continue to drink, particularly women 1

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

• Brief motivational interventions should be routinely used 1
• Cognitive behavioral therapy enhances naltrexone efficacy 4
• Integrating addiction treatment with medical care remains the best option for advanced ALD 1

Common Pitfalls to Avoid

1. Do not prescribe naltrexone to patients with any degree of liver dysfunction - the hepatotoxicity risk outweighs benefits even though it's highly effective in non-cirrhotic patients 1

2. Do not start naltrexone without ensuring opioid-free status - requires minimum 7-10 days off short-acting opioids, up to 2 weeks for buprenorphine/methadone 3

3. Do not use long-acting benzodiazepines in cirrhotic patients - opt for lorazepam or oxazepam to reduce encephalopathy risk 1

4. Do not prescribe baclofen to patients with active hepatic encephalopathy - it may worsen mental status 1

5. Do not use disulfiram in any patient with alcoholic liver disease - unacceptable hepatotoxicity risk 1, 5