What medications are used to treat alcohol abuse?

Medications for Alcohol Abuse

For patients with normal liver function, naltrexone 50 mg daily or acamprosate 666 mg three times daily are first-line FDA-approved medications that should be combined with psychosocial interventions; however, for patients with alcoholic liver disease or elevated liver enzymes, baclofen 30-60 mg daily is the only medication proven safe and effective in this population. 1

FDA-Approved First-Line Medications

Naltrexone (for patients with normal liver function)

• Naltrexone 50 mg once daily reduces the risk of relapse to heavy drinking with a number needed to treat of approximately 20 to prevent return to any drinking 1
• Naltrexone works as an opioid receptor antagonist that controls alcohol craving and reduces drinking frequency, though it does not substantially enhance complete abstinence 2, 1
• Naltrexone is contraindicated in patients with alcoholic liver disease due to documented hepatotoxicity risk 2, 1
• The FDA label confirms naltrexone undergoes >98% hepatic metabolism and can cause hepatocellular injury 3

Acamprosate (safe in liver disease)

• Acamprosate 666 mg three times daily (1,998 mg/day for patients ≥60 kg) reduces drinking frequency with a number needed to treat of approximately 12 1
• Acamprosate has structural similarities to GABA and reduces withdrawal symptoms including alcohol craving, being more effective at maintaining rather than inducing remission 2
• Acamprosate has no hepatic metabolism and no reported instances of hepatotoxicity, making it the safest FDA-approved option for patients with liver disease 1
• Acamprosate is most effective in detoxified alcoholics when combined with counseling and support, but has not shown significant impact in patients who have not achieved initial abstinence 2

Preferred Medication for Alcoholic Liver Disease

Baclofen (first choice for liver disease)

• Baclofen 30-60 mg daily (typically 10 mg three times daily) is the only medication specifically studied and proven safe in patients with compensated and decompensated cirrhosis 1, 4
• Baclofen, a GABA-B receptor agonist, has demonstrated improved rates of total alcohol abstinence and decreased relapse over 1 year in patients with cirrhosis 1
• Baclofen should not be used in patients with hepatic encephalopathy due to risk of impaired mentation 1
• One randomized clinical trial in patients with cirrhosis demonstrated benefit in achieving and maintaining abstinence with baclofen 2

Medications to Avoid in Liver Disease

Disulfiram (contraindicated in severe liver disease)

• Disulfiram should be avoided in patients with severe alcoholic liver disease due to possible hepatotoxicity, including hepatic failure resulting in transplantation or death 2, 1
• The FDA label warns that severe and sometimes fatal hepatitis may develop even after many months of therapy, and patients should be monitored with baseline and follow-up liver function tests every 10-14 days 5
• Disulfiram works by inhibiting aldehyde dehydrogenase, causing acetaldehyde buildup and creating an aversive reaction when combined with alcohol 4

Promising Off-Label Medications

Gabapentin

• Gabapentin 600-1,800 mg daily has shown effectiveness in treating alcohol use disorder and is safe in liver disease with no hepatotoxicity risk 1
• The European Association for the Study of the Liver identifies gabapentin as a promising medication under preliminary research for alcohol withdrawal syndrome 6

Topiramate

• Topiramate 75-400 mg daily has demonstrated efficacy in reducing heavy drinking and may decrease liver enzyme levels, but has not been specifically tested in patients with alcoholic liver disease 6, 1
• Topiramate shows promise for both alcohol withdrawal syndrome and relapse prevention 2

Management of Acute Alcohol Withdrawal

Benzodiazepines (gold standard for withdrawal)

• Benzodiazepines are the gold standard treatment for alcohol withdrawal syndrome, with lorazepam being the preferred agent for patients with liver dysfunction due to its shorter half-life and lack of active metabolites 6, 1
• Short and intermediate-acting benzodiazepines (lorazepam, oxazepam) are safer in patients with hepatic dysfunction compared to long-acting ones (diazepam, chlordiazepoxide) 2, 6
• Benzodiazepines should not be continued beyond 10-14 days due to potential for abuse 1

Essential Thiamine Supplementation

• Thiamine 100-300 mg daily for 4-12 weeks is crucial to prevent Wernicke encephalopathy and must be given before any glucose-containing IV fluids 6, 1

Critical Implementation Points

Opioid-Free Period Before Naltrexone

• Patients must be opioid-free (including tramadol) for a minimum of 7-10 days before starting naltrexone to avoid precipitated withdrawal 3
• Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks 3
• A naloxone challenge test should be performed if there is any question of occult opioid dependence 3

Combination with Psychosocial Support

• All pharmacological treatments must be combined with psychosocial support and counseling for optimal outcomes, as medications alone have modest effect sizes 2, 1, 4
• Naltrexone or acamprosate should be considered in combination with counseling to decrease the likelihood of relapse in patients who achieve abstinence 2

Monitoring Requirements

• Regular liver function tests should be performed to assess improvement and monitor for medication effects 6, 1
• Alcohol abstinence remains the most important intervention for improving survival and preventing progression to cirrhosis 1, 4

Clinical Algorithm for Medication Selection

For patients with normal liver function:

• Start naltrexone 50 mg daily OR acamprosate 666 mg three times daily 1
• Ensure 7-10 day opioid-free period before naltrexone 3
• Combine with intensive psychosocial support 2

For patients with alcoholic liver disease or elevated liver enzymes:

• Use baclofen 10 mg three times daily (30-60 mg/day total) as first-line therapy 1, 4
• Alternative: acamprosate (safe in liver disease) 1
• Never use naltrexone or disulfiram 2, 1
• Consider gabapentin as off-label alternative 1

For acute alcohol withdrawal:

• Use lorazepam (preferred in liver dysfunction) 6, 1
• Administer thiamine before glucose 6, 1
• Limit benzodiazepines to 10-14 days maximum 1