What is the role of medications like disulfiram, naltrexone, or acamprosate in treating alcohol use disorder?

Medications for Alcohol Use Disorder

For patients with alcohol use disorder, psychosocial treatment is first-line, but should be combined with pharmacotherapy—specifically naltrexone, acamprosate, or disulfiram—to reduce relapse and maintain abstinence, with the choice depending on liver function status and patient-specific factors. 1

Treatment Framework

Psychosocial Interventions as Foundation

• Brief motivational interventions should be routinely used in all patients with alcohol use disorder, incorporating the "five As" model: Ask about use, Advice to quit or reduce, Assess willingness, Assist to quit or reduce, and Arrange follow-up 1
• Brief interventions reduce drinking by an average of 57 grams per week in men and decrease alcohol-related morbidity and mortality 1
• All pharmacotherapy must be combined with counseling and psychosocial support—medications alone without proper motivation and supportive therapy are unlikely to have substantive effects 1, 2

Medication Selection Algorithm

For Patients WITHOUT Advanced Liver Disease

Naltrexone is the preferred first-line agent for patients without hepatic concerns, as it demonstrates superior efficacy in preventing return to any drinking with a number needed to treat (NNT) of approximately 20 3, 4

• Naltrexone reduces relapse rates, decreases cravings, and increases abstinence rates by competitively blocking opioid receptors, thereby blocking the effects of endogenous opioids that may reinforce alcohol consumption 4, 5, 6
• Dosing: 50 mg orally once daily 4
• Critical caveat: Naltrexone undergoes hepatic metabolism and carries hepatotoxicity concerns, making it contraindicated in patients with advanced alcoholic liver disease 3

Acamprosate is equally effective and should be considered as an alternative first-line option, particularly for maintaining continuous abstinence once achieved 3, 7

• Acamprosate reduces relapse rates, maintains abstinence, and decreases severity of relapse by modulating NMDA receptor transmission 8, 5, 6
• Timing is critical: Must be initiated 3-7 days after last alcohol consumption and only after withdrawal symptoms have resolved—starting too early reduces efficacy since its mechanism is maintaining rather than inducing abstinence 8, 3
• Dosing: 666 mg (two 333 mg tablets) three times daily for patients ≥60 kg; reduce dose by one-third for patients <60 kg 8, 3
• Treatment duration: 3-6 months minimum, can extend to 12 months 8, 3

Disulfiram is a third-line option with mixed evidence, best reserved for highly motivated patients with supervised administration 1, 2

• Disulfiram is an aversive agent that causes unpleasant reactions when alcohol is consumed, but has significant compliance difficulties and no clear evidence of increasing abstinence rates 2, 5, 6
• Major limitation: Requires patient motivation and is unlikely to be effective without proper supportive therapy 2

For Patients WITH Advanced Alcoholic Liver Disease

Acamprosate is strongly preferred because it undergoes no hepatic metabolism and has no reported instances of hepatotoxicity 3

• Unlike naltrexone, acamprosate is not metabolized by the liver, making it the safest choice for patients with alcoholic liver disease 8, 3
• Follow the same dosing and timing guidelines as above 8, 3

Baclofen may be considered as an alternative in advanced liver disease, though evidence is more limited 1

• Recent studies suggest baclofen is safe and effective to prevent alcohol relapse in patients with advanced alcoholic liver disease 1
• Important caveat: This recommendation is based on lower-quality evidence (B2 level) compared to acamprosate 1

Naltrexone and disulfiram cannot be recommended in patients with advanced liver disease due to potential hepatotoxicity and side effects 1

Special Population: Pregnancy

For pregnant women with alcohol use disorder, psychosocial treatment is first-line, with medication use highly individualized 1

• Disulfiram is contraindicated due to association with fetal abnormalities 1
• Naltrexone and acamprosate have limited safety data but did not show fetal abnormalities in available studies—the decision to use must weigh risks of medication exposure against risks of continued alcohol use 1
• Baclofen should be used with caution as it may accumulate and potentially cause neonatal withdrawal syndrome 1
• Delaying conception until abstinence is achieved is strongly recommended 1

Acute Withdrawal Management

Benzodiazepines are the treatment of choice for acute alcohol withdrawal syndrome, alleviating withdrawal discomfort and preventing/treating seizures and delirium 1

• All patients undergoing withdrawal should receive oral thiamine 1
• Patients at high risk (malnourished, severe withdrawal) or with suspected Wernicke's encephalopathy should receive parenteral thiamine 1
• Do not start acamprosate during acute withdrawal—wait until withdrawal symptoms have resolved 8, 3

Common Pitfalls to Avoid

• Starting acamprosate too early (immediately after sobering up or during withdrawal) reduces efficacy since it works best for maintaining abstinence rather than inducing it 8, 3
• Using naltrexone in patients with liver disease risks hepatotoxicity and is contraindicated in advanced alcoholic liver disease 3
• Failing to combine medications with psychosocial support—all guidelines emphasize that pharmacotherapy alone is insufficient 1, 3
• Discontinuing treatment prematurely—acamprosate should be continued for at least 3-6 months for optimal results 8, 3
• Not screening for alcohol use routinely using validated tools like the AUDIT questionnaire 1