What is the use of Acomprosate (Campral) in treating alcohol dependence?

Acamprosate for Alcohol Dependence

Acamprosate (Campral) is the only medication with sufficient high-quality evidence to definitively recommend for maintaining abstinence in alcohol-dependent patients who have already been detoxified and achieved initial abstinence. 1

FDA-Approved Indication

• Acamprosate is indicated specifically for maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. 2
• The medication must be part of a comprehensive management program that includes psychosocial support. 2
• Efficacy has NOT been demonstrated in patients who have not undergone detoxification and achieved abstinence prior to starting treatment—this is a critical distinction. 2

Clinical Algorithm for Use

Patient Selection Criteria

• Only use in patients who have completed detoxification and are currently abstinent. 2
• Do not initiate in patients still actively drinking—the drug will not work in this population. 2
• Screen for renal function before initiating therapy. 2

Dosing

• Standard dose: 666 mg (two 333 mg tablets) three times daily (total 1998 mg/day). 2
• Moderate renal impairment (CrCl 30-50 mL/min): Reduce to 333 mg three times daily. 2
• Severe renal impairment (CrCl ≤30 mL/min): Contraindicated—do not use. 2

Duration of Treatment

• Treatment typically ranges from 3-12 months based on clinical trial evidence. 3
• Continue as long as the patient maintains abstinence and tolerates the medication. 3

Evidence Quality and Comparative Effectiveness

The 2020 BMJ network meta-analysis found acamprosate to be the only intervention with enough high-quality evidence to conclude superiority over placebo for maintaining abstinence in detoxified patients. 1

Comparison with Other Medications

• Acamprosate vs. Naltrexone: Meta-analyses show similar efficacy between the two agents. 3
• Acamprosate vs. Disulfiram: Limited evidence supports disulfiram's effect on abstinence, whereas acamprosate has robust evidence. 1
• WHO guidelines recommend acamprosate, disulfiram, or naltrexone, with the decision based on patient preferences, motivation, and availability. 1
• EASL guidelines note that acamprosate is confirmed effective through meta-analysis of 24 randomized controlled trials. 1

Specific Advantages in Liver Disease

• Acamprosate is NOT metabolized by the liver, making it uniquely suitable for patients with hepatic impairment. 4
• Can be administered to patients with hepatitis or liver disease, unlike naltrexone which has hepatotoxicity concerns. 4
• Not impacted by alcohol use, so can theoretically continue if patient has a slip (though FDA indication requires abstinence at initiation). 4
• Hepatology guidelines recommend naltrexone OR acamprosate in combination with counseling for patients with alcohol-induced liver disease who achieve abstinence. 1

Mechanism of Action

• Acamprosate is a synthetic taurine analogue that modulates glutamatergic neurotransmission. 5
• It restores balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters that are disrupted by chronic alcohol exposure. 4
• The drug reduces withdrawal-associated distress and attenuates craving induced by alcohol priming. 4, 6
• Research shows acamprosate reduces subjective craving and cortisol elevation following an alcohol slip, suggesting it may prevent full relapse after a single drink. 6

Expected Outcomes

What Acamprosate Does Well

• Increases complete abstinence rates compared to placebo. 5, 3
• Prolongs time to first drink after initiating treatment. 5, 3
• Increases cumulative abstinence duration over treatment period. 5, 3
• Increases percentage of alcohol-free days. 3

What Acamprosate Does NOT Do

• Does not reduce heavy drinking days in patients who relapse—it's an abstinence medication, not a harm-reduction medication. 4
• Does not work in patients who haven't achieved initial abstinence—detoxification must occur first. 2

Safety and Tolerability

• Excellent safety profile with low propensity for drug interactions. 3
• Most common adverse effects (≥3% and greater than placebo): diarrhea, flatulence, nausea, anxiety, depression, dizziness, insomnia, pruritus, sweating. 2
• Monitor for depression or suicidal ideation—prompt patients and families to report such symptoms immediately. 2
• Low bioavailability but this does not impact clinical efficacy. 4
• Not metabolized by liver, making it safer than naltrexone in patients with hepatic disease. 4

Critical Clinical Pitfalls to Avoid

1. Do not prescribe to patients still drinking—this is the most common error. The drug only works in abstinent patients. 2
2. Do not use as monotherapy—always combine with psychosocial support or the efficacy is substantially reduced. 2
3. Do not prescribe in severe renal impairment (CrCl ≤30)—this is an absolute contraindication. 2
4. Do not forget to reduce dose in moderate renal impairment—failure to adjust can lead to drug accumulation. 2
5. Do not expect it to reduce heavy drinking—if the patient relapses, acamprosate won't minimize the severity of drinking episodes. 4

Combination Therapy Considerations

• Adding naltrexone to acamprosate does not appear to improve efficacy beyond either agent alone. 1, 4
• Adding cognitive-behavioral therapy does not enhance acamprosate's pharmacological effect, though psychosocial support is still required per FDA labeling. 4
• Complementary interventions like home visits may be considered to enhance overall treatment effects. 1