What FDA‑approved medication should I start for a motivated patient with alcohol use disorder, considering liver function, renal function, opioid use, pregnancy status, and need for psychosocial support?

Starting Anti-Alcohol Medications

For a motivated patient with alcohol use disorder and normal liver function, start oral naltrexone 25 mg daily for 3 days, then increase to 50 mg daily for 3–6 months, combined with psychosocial therapy; however, if the patient has any alcoholic liver disease, elevated liver enzymes, or cirrhosis, naltrexone is absolutely contraindicated and you must instead prescribe baclofen 10 mg three times daily, titrated gradually over 12 weeks. 1

Critical Pre-Treatment Assessment

Before prescribing any medication, you must:

• Obtain baseline liver function tests to screen for alcoholic liver disease, acute hepatitis, or cirrhosis 1
• Check renal function (creatinine clearance) because acamprosate requires dose adjustment or is contraindicated in renal impairment 1
• Screen for current opioid use, as naltrexone will precipitate acute withdrawal in opioid-dependent patients 2
• Confirm pregnancy status in women of childbearing age 3
• Ensure the patient is not in active alcohol withdrawal – all maintenance medications must wait until withdrawal is complete 1, 2

Managing Active Withdrawal First (Days 1–7)

Never start naltrexone, acamprosate, or baclofen during active withdrawal – doing so provides no benefit and delays appropriate treatment. 1

• Benzodiazepines are the gold standard for alcohol withdrawal, reducing symptoms and preventing seizures and delirium tremens 1, 2
• In patients with liver dysfunction, use short- or intermediate-acting agents: lorazepam 1–4 mg every 4–8 hours or oxazepam 1
• In patients with normal liver function, long-acting benzodiazepines (diazepam, chlordiazepoxide) provide superior seizure protection 1
• Administer thiamine 100–300 mg daily for 4–12 weeks before any intravenous glucose to prevent Wernicke-Korsakoff encephalopathy 1
• Correct magnesium deficits and other electrolyte disturbances 1

First-Line Medication Selection Algorithm

If Liver Function Is Normal (No ALD, Normal LFTs):

Option 1: Naltrexone (harm-reduction focus)

• Start 25 mg orally daily for days 1–3, then increase to 50 mg daily 4, 1, 2
• Continue for 3–6 months (up to 12 months) 4, 1
• Begin only 3–7 days after the last drink and after complete resolution of withdrawal symptoms 4, 1, 2
• Monitor liver enzymes every 3–6 months during treatment 1, 2
• Number needed to treat = 20 to prevent any drinking; reduces binge-drinking risk by ~10% 1, 5
• Alternative: extended-release injectable naltrexone 380 mg intramuscularly once monthly 1, 6

Option 2: Acamprosate (abstinence focus)

• Dose: 666 mg (two 333 mg tablets) orally three times daily for patients ≥60 kg 1, 3
• Reduce by one-third for patients <60 kg 4
• Initiate 3–7 days after the last drink, once withdrawal has resolved 4, 1
• Continue for 3–6 months 4
• Safe in any degree of liver disease because it has no hepatic metabolism and zero hepatotoxicity risk 1
• Number needed to treat = 12 for achieving abstinence 1, 6
• Contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min); dose-reduce for moderate impairment (30–50 mL/min) 1, 3

If Alcoholic Liver Disease, Elevated LFTs, or Cirrhosis Is Present:

Naltrexone is absolutely contraindicated – it carries documented hepatotoxicity risk and is metabolized by the liver. 4, 1, 2

First-line: Baclofen

• Baclofen is the only medication with proven safety and efficacy in randomized controlled trials specifically in cirrhotic patients 1, 7
• Start 10 mg orally three times daily; titrate gradually over 12 weeks to a target of 30–80 mg per day 1, 7
• Use slower titration in severe liver disease for safety 1
• Exclude patients with hepatic encephalopathy because baclofen may worsen mentation 1
• Unique advantage: Baclofen can be initiated safely in patients who are still actively drinking, whereas acamprosate requires 3–7 days of abstinence 7

Alternative: Acamprosate

• Same dosing as above (666 mg three times daily) 1
• Safe across all stages of liver disease with no dose adjustment needed for hepatic dysfunction 1
• Must wait 3–7 days after last drink to initiate 4, 1

Second-line: Gabapentin

• Dose: up to 1800 mg per day (600 mg three times daily) for at least 12 weeks 1
• Not metabolized by the liver; eliminated renally with no hepatotoxicity risk 1
• Number needed to treat = 8 for abstinence, 5 for non-excessive drinking 1
• Monitor renal function and mental status closely 1

Medications to Absolutely Avoid

• Disulfiram should be avoided in severe alcoholic liver disease due to potential hepatotoxicity 4, 1, 8
• Disulfiram is generally recommended as second-line treatment for most patients due to safety concerns and lack of high-quality comparative studies 8
• Naltrexone must never be prescribed to any patient with elevated liver enzymes or any hepatic dysfunction from alcohol 4, 1, 2

Essential Psychosocial Integration

All pharmacologic regimens must be combined systematically with psychosocial therapies – medication alone is insufficient. 4, 1

• Individual psychotherapy, psychoeducation, group therapy, and cognitive-behavioral therapy 4, 1
• Motivational interviewing delivered in a non-judgmental, non-confrontational manner 7
• The "Five A's" model (Ask, Advise, Assess, Assist, Arrange) at each visit 7
• Encourage active involvement in Alcoholics Anonymous or similar peer support 4
• Family therapy and education – alcohol dependence is a dysfunctional family disorder 4
• Combined CBT and pharmacotherapy yields modest but significant benefit (effect size 0.18–0.28) 1

Common Pitfalls to Avoid

• Never initiate naltrexone during active withdrawal – it can precipitate a hyperacute withdrawal syndrome due to opioid-receptor antagonism 1, 2
• Do not prescribe naltrexone to patients with any liver disease – this is the most common and dangerous error 4, 1, 2
• Do not forget to check renal function before starting acamprosate – severe renal impairment is an absolute contraindication 1, 3
• Do not omit psychosocial interventions – pharmacotherapy alone has limited efficacy 4, 1
• Do not delay baclofen initiation until complete abstinence in cirrhotic patients – starting while still drinking is a key advantage 7

Expected Clinical Outcomes

• Sustained abstinence improves outcomes across all stages of alcoholic liver disease, lowering portal pressure and preventing progression to cirrhosis 1
• Naltrexone and acamprosate produce modest effect sizes (~0.15–0.20) but, when paired with psychosocial treatment, reduce relapse rates from 54–60% to 23–31% 1
• Brief interventions lower morbidity and mortality related to drinking 4