Which pharmacologic agent is appropriate for a patient who wants to stop drinking alcohol?

Pharmacotherapy for Alcohol Use Disorder

For patients without liver disease, start with either oral naltrexone 50 mg daily or acamprosate 666 mg three times daily (1,998 mg/day), but for patients with alcoholic liver disease or cirrhosis, baclofen is the only safe and validated option. 1

Treatment Algorithm Based on Liver Function

Step 1: Assess Liver Function Before Selecting Medication

• Obtain baseline liver function tests and assess for presence of alcoholic liver disease, acute hepatitis, or cirrhosis before initiating any pharmacotherapy. 1
• Check renal function (creatinine clearance) as acamprosate requires dose adjustment or is contraindicated in renal impairment. 1

Step 2: First-Line Medications for Patients WITHOUT Significant Liver Disease

Naltrexone (Preferred for Harm Reduction Goals):

• Start naltrexone 25 mg daily for days 1-3, then increase to 50 mg daily for 3-6 months (up to 12 months). 2
• Critical timing: Initiate naltrexone only 3-7 days after the last alcohol consumption and after all withdrawal symptoms have completely resolved. 1, 2
• Naltrexone reduces the risk of relapse to heavy drinking with a number needed to treat of 18, and prevents return to any drinking with a number needed to treat of 11. 3
• Monitor liver function tests every 3-6 months during treatment. 1
• Common side effects include nausea (risk ratio 1.73) and vomiting (risk ratio 1.53) compared to placebo. 3
• Injectable extended-release naltrexone 380 mg intramuscularly once monthly is an alternative that improves compliance and reduces drinking days by approximately 5 days per month. 2, 3

Acamprosate (Preferred for Complete Abstinence Goals):

• Start acamprosate 666 mg three times daily (1,998 mg/day total) for patients weighing ≥60 kg. 1
• Initiate 3-7 days after last alcohol consumption, after withdrawal symptoms resolve. 2
• Acamprosate prevents return to any drinking with a number needed to treat of 11. 3
• Acamprosate has no hepatotoxicity risk and is safe in liver disease, making it preferable when liver function is uncertain. 1
• Contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min); reduce dose for moderate impairment (30-50 mL/min). 1
• Common side effect is diarrhea (risk ratio 1.58 compared to placebo). 3

Step 3: Medications for Patients WITH Alcoholic Liver Disease or Cirrhosis

Baclofen (ONLY Safe Option in Cirrhosis):

• Baclofen 30-80 mg per day is the only pharmacologic agent tested and validated for maintaining abstinence in cirrhotic patients. 4, 1
• Start after withdrawal symptoms have resolved and titrate gradually over 12 weeks. 4
• In severe liver disease, use a slower titration schedule to enhance safety. 4
• Baclofen acts as a GABA-B receptor agonist, reducing craving and preventing relapse. 4

Gabapentin (Second-Line for Liver Disease):

• Gabapentin 1,800 mg daily (600 mg three times daily) is a second-line option particularly effective in patients with liver disease. 4, 1
• Number needed to treat is 8 for abstinence and 5 for non-excessive drinking. 1

Step 4: Medications to AVOID in Liver Disease

Naltrexone Contraindications:

• Naltrexone is absolutely contraindicated in alcoholic liver disease, acute hepatitis, or decompensated cirrhosis due to hepatotoxicity risk. 4, 1, 2
• Do not use naltrexone in patients with elevated liver enzymes or any degree of hepatic dysfunction from alcohol. 5, 2

Disulfiram Contraindications:

• Disulfiram should be avoided in severe alcoholic liver disease due to potential hepatotoxic effects. 4
• Disulfiram is no longer considered first-line treatment due to compliance difficulties and toxicity concerns. 6, 7

Critical Timing: Manage Withdrawal FIRST, Then Start Maintenance Therapy

Acute Withdrawal Management (Days 1-7)

• Benzodiazepines are the gold standard for acute alcohol withdrawal syndrome, reducing withdrawal symptoms and preventing seizures and delirium tremens. 5, 4, 2
• For patients with hepatic dysfunction, use short- or intermediate-acting benzodiazepines: lorazepam 1-4 mg every 4-8 hours or oxazepam. 4
• Long-acting benzodiazepines (diazepam, chlordiazepoxide) provide superior protection against seizures and delirium in patients without liver disease. 5, 2
• Administer thiamine 100-300 mg daily for 4-12 weeks before any intravenous glucose to prevent Wernicke-Korsakoff encephalopathy. 4
• Correct electrolyte disturbances, especially magnesium deficits. 4

Common Pitfall to Avoid

• Never start naltrexone, acamprosate, or baclofen during active withdrawal—these medications provide no benefit for withdrawal symptoms and delay appropriate benzodiazepine therapy. 2
• Naltrexone initiated during withdrawal can precipitate a hyperacute withdrawal syndrome due to its opioid receptor antagonism. 2

Essential Psychosocial Integration

• All pharmacologic treatment must be combined systematically with psychosocial interventions including individual psychotherapy, psycho-education, group therapy, and cognitive-behavioral therapy. 4
• Naltrexone effectiveness is highly dependent on treatment compliance; efficacy improves dramatically in patients who attend counseling sessions and take medication consistently. 8
• When used alone without proper motivation and supportive therapy, pharmacotherapy is unlikely to have substantive effect on drinking patterns. 6

Clinical Outcomes of Treatment

• Sustained alcohol abstinence improves clinical outcomes at all stages of alcoholic liver disease, lowering portal pressure and preventing progression to cirrhosis. 4
• Both naltrexone and acamprosate have modest effect sizes (0.15-0.2 range) but provide clinically meaningful reductions in relapse rates from 54-60% to 23-31% when combined with psychosocial treatment. 2, 9