What is the appropriate dosing for acamprosate in a patient with Major Depressive Disorder (MDD) on Latuda (lurasidone) who has not responded to naltrexone for substance use management?

Acamprosate Dosing for Alcohol Use Disorder When Naltrexone Fails

The standard dose of acamprosate is 666 mg (two 333 mg tablets) three times daily for a total of 1998 mg/day, which should be initiated as soon as possible after alcohol withdrawal when abstinence is achieved. 1

Standard Dosing Regimen

• Standard dose: 666 mg three times daily (total 1998 mg/day) 1
• Timing: Can be taken without regard to meals, though dosing with meals was used in clinical trials and may be helpful for patients who eat three regular meals daily 1
• Initiation: Start as soon as possible after the alcohol withdrawal period once the patient has achieved abstinence 1
• Duration: Continue treatment even if the patient relapses, as part of comprehensive psychosocial treatment 1

Dose Modifications for Renal Impairment

For patients with moderate renal impairment (creatinine clearance 30-50 mL/min), reduce the dose to 333 mg three times daily (total 999 mg/day). 1

• Severe renal impairment (creatinine clearance ≤30 mL/min): Acamprosate is contraindicated 1

Considerations in Liver Disease

The presence of liver disease does not change the indications or dosing conditions for acamprosate, making it particularly advantageous when naltrexone is contraindicated or ineffective. 2

• Unlike naltrexone, which is contraindicated in hepatic insufficiency, acamprosate has no hepatic metabolism and has not been shown to cause hepatotoxicity 2
• This makes acamprosate the preferred choice in patients with alcohol-associated liver disease who cannot tolerate naltrexone 2

Evidence Supporting Acamprosate Use

Acamprosate is the only pharmacological intervention with sufficient evidence demonstrating superiority over placebo in maintaining abstinence for up to 12 months in primary care settings. 2

• Network meta-analysis showed acamprosate significantly improved maintenance of abstinence compared to placebo (odds ratio 1.86,95% CI 1.49-2.33), with moderate quality evidence 2
• Acamprosate reduces withdrawal symptoms including alcohol craving and is more effective at maintaining rather than inducing remission when combined with counseling 2
• The number needed to treat to prevent return to any drinking is approximately 12 for acamprosate 2

Combination Therapy Considerations

If acamprosate monotherapy proves insufficient, combination with naltrexone can be considered if liver function permits, as there is no pharmacokinetic contraindication to co-administration. 3

• Co-administration of acamprosate with naltrexone increases acamprosate absorption by 33% but does not affect naltrexone pharmacokinetics 3
• Combination therapy (acamprosate plus naltrexone) showed improved outcomes in some studies (odds ratio 3.68,95% CI 1.50-9.02 for abstinence) 2
• However, the added benefit of combination therapy over monotherapy remains controversial 2

Special Considerations for MDD Patients on Lurasidone

In patients with major depressive disorder on lurasidone, acamprosate can be safely added without known drug interactions, as acamprosate has no hepatic metabolism and minimal drug interaction potential. 1, 4

• A pilot study demonstrated that acamprosate augmentation of escitalopram (an SSRI) in patients with concurrent MDD and alcohol use disorder was associated with significant reduction in alcohol use frequency 4
• Acamprosate's mechanism (NMDA receptor antagonist with GABA-like properties) does not interact with lurasidone's dopamine-serotonin receptor antagonism 1, 5

Common Pitfalls to Avoid

• Do not reduce the dose below 333 mg three times daily unless moderate renal impairment is present, as lower doses may be less effective 1
• Do not discontinue acamprosate if the patient relapses—continue treatment as it remains effective in reducing severity and frequency of relapses 1
• Do not use acamprosate as monotherapy—it must be part of comprehensive psychosocial treatment for optimal outcomes 1, 2
• Do not assume acamprosate works in actively drinking patients—it is most effective in maintaining abstinence after detoxification, not in inducing initial abstinence 2