What is the efficacy of acamprosate (acamprosate calcium) for alcohol use disorder (AUD)?

Efficacy of Acamprosate for Alcohol Use Disorder

Acamprosate is effective for maintaining abstinence from alcohol in patients with alcohol use disorder who are already abstinent at treatment initiation, with moderate quality evidence supporting its use as part of a comprehensive treatment program. 1

Mechanism of Action and Pharmacology

Acamprosate works by:

• Modulating the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters
• Reducing withdrawal effects and alcohol craving
• Normalizing brain glutamate levels that are disrupted during chronic alcohol use

The medication reaches its desired concentration within 1-2 weeks of starting treatment and is primarily eliminated through the kidneys rather than the liver, making it suitable for patients with liver disease (common in alcohol use disorder). 1

Efficacy Evidence

Acamprosate has demonstrated efficacy in:

• Maintaining abstinence in detoxified alcohol-dependent patients
• Increasing the cumulative duration of abstinence
• Reducing the risk of returning to any drinking

A systematic review and network meta-analysis published in the BMJ (2020) found that acamprosate was the only intervention with sufficient evidence to conclude it is better than placebo for supporting abstinence in detoxified alcohol-dependent patients for up to 12 months. 1

Key efficacy points:

• Acamprosate has demonstrated its efficacy in more than 25 placebo-controlled trials
• It is most effective when started 3-7 days after the last alcohol consumption, after withdrawal symptoms have resolved
• The medication is less effective for reducing heavy drinking days compared to maintaining complete abstinence

Dosing and Administration

Standard dosing:

• 666 mg (two 333 mg tablets) three times daily (total 1,998 mg/day)
• For patients weighing <60 kg: reduce dose by one-third
• Treatment duration: typically 3-6 months, but can be extended up to 12 months
• Should be initiated as soon as possible after alcohol withdrawal when the patient has achieved abstinence

For patients with moderate renal impairment (creatinine clearance 30-50 mL/min):

• Reduce to one 333 mg tablet three times daily
• Contraindicated in severe renal impairment (creatinine clearance ≤30 mL/min) 2

Limitations and Considerations

Important limitations to consider:

• Efficacy has not been demonstrated in patients who have not undergone detoxification
• Not proven effective in patients who haven't achieved abstinence before starting treatment
• Limited evidence for efficacy in polysubstance abusers 2
• Some studies show no significant benefit over placebo in family medicine settings 3

Comparison with Other Medications

When comparing FDA-approved treatments for alcohol dependence:

• Acamprosate has an excellent safety and tolerability profile
• Unlike naltrexone and disulfiram, acamprosate is not metabolized by the liver
• Can be administered to patients with hepatitis or liver disease
• Can be used even if the patient continues to drink alcohol 4

Integration with Psychosocial Treatment

For optimal outcomes:

• Acamprosate should be part of a comprehensive management program that includes psychosocial support 2
• Brief interventions using the FRAMES model (Feedback, Responsibility, Advice, Menu, Empathy, Self-efficacy) have been shown to lower morbidity and mortality related to drinking 1, 5
• Psychosocial treatments including cognitive behavioral therapy, motivational enhancement therapy, and 12-step facilitation should be incorporated 5

Practical Treatment Algorithm

1. Patient Selection:

   • Confirm alcohol dependence diagnosis
   • Ensure patient has undergone detoxification and is abstinent
   • Assess renal function (contraindicated if severe impairment)

2. Initiation:

   • Start 3-7 days after last alcohol consumption
   • Standard dose: 666 mg three times daily
   • Adjust dose based on weight and renal function

3. Monitoring:

   • Regular follow-up to assess abstinence
   • Monitor for adverse effects (primarily gastrointestinal)
   • Continue medication even if patient relapses

4. Duration:

   • Typical treatment period: 3-6 months
   • May extend up to 12 months in some cases

5. Concurrent Treatment:

   • Implement psychosocial interventions
   • Consider nutritional support if malnourished

Conclusion

Acamprosate represents an effective pharmacological option for maintaining abstinence in patients with alcohol use disorder who have already achieved initial abstinence. Its unique mechanism of action, favorable safety profile (especially for patients with liver disease), and demonstrated efficacy make it a valuable tool when combined with appropriate psychosocial interventions.