Can a patient with anxiety and alcohol use disorder, taking Acamprosate (Campral) 666mg three times a day (TID), have their medication decreased to 666mg twice a day (BID) to alleviate anxiety symptoms?

Acamprosate Dose Reduction for Anxiety: Clinical Recommendation

No, acamprosate should not be reduced from 666mg TID to 666mg BID to manage anxiety symptoms, as this represents a 33% dose reduction below the FDA-approved therapeutic dose and is not supported by evidence. 1

Standard Dosing Requirements

The FDA-approved dosing for acamprosate is explicit and non-negotiable for therapeutic efficacy:

• Standard dose: 666mg (two 333mg tablets) three times daily for patients ≥60kg 1
• Reduced dose: 666mg twice daily (1332mg/day total) is only indicated for patients weighing <60kg 2
• Renal impairment dosing: 333mg three times daily for creatinine clearance 30-50 mL/min 1

Your proposed reduction to 666mg BID would deliver only 1332mg/day in a patient who presumably weighs ≥60kg (since they're on the full dose), which represents subtherapeutic dosing without clinical justification. 1

Addressing the Anxiety Concern

The anxiety this patient is experiencing requires a different clinical approach than dose reduction:

First, Determine the Source of Anxiety

• Is this residual alcohol withdrawal? Acamprosate should only be initiated 3-7 days after the last alcohol consumption and after withdrawal symptoms have resolved. 3, 1 If started too early, ongoing withdrawal symptoms (including anxiety) may persist.

• Is this pre-existing anxiety disorder? Behavioral therapy specifically trains patients to use methods other than alcohol to alleviate anxiety, including relaxation therapy and assertive training. 4 Psychiatric consultation is recommended for comprehensive psychosocial treatment. 4

Evidence on Acamprosate and Anxiety

Interestingly, acamprosate may actually reduce anxiety rather than cause it:

• Acamprosate diminishes arousal, anxiety, and insomnia through its modulation of NMDA receptor transmission and restoration of the GABA-glutamate balance. 5

• One open-label study showed acamprosate reduced anxiety symptoms (mean HAM-A score reduction from 20 to 8.87) when used as augmentation therapy at the full dose of 1998mg/day. 6 Notably, 62% of patients achieved remission of anxiety symptoms. 6

• The modal effective dose for anxiety reduction was 1998mg/day (the full therapeutic dose), not a reduced dose. 6

Clinical Algorithm for This Patient

Step 1: Verify the patient is truly abstinent and past the withdrawal period (3-7 days post-last drink). 3, 1

Step 2: Ensure acamprosate is combined with comprehensive psychosocial support, which is essential for efficacy. 1, 4

Step 3: If anxiety persists despite proper timing and psychosocial support:

• Consider psychiatric consultation for formal anxiety disorder evaluation 4
• Implement behavioral therapy interventions (relaxation therapy, assertive training, cognitive behavioral therapy) 4
• If a separate anxiety disorder is diagnosed, consider evidence-based anxiolytic therapy in addition to (not instead of) full-dose acamprosate 6

Step 4: Maintain the full therapeutic dose of 1998mg/day for at least 3-6 months, as clinical benefit emerges over sustained treatment. 2

Critical Safety Advantage

Acamprosate has no hepatotoxicity and is the preferred agent for patients with alcohol-associated liver disease. 2 Unlike naltrexone (contraindicated in alcoholic liver disease) and disulfiram (avoided in severe liver disease), acamprosate is not metabolized by the liver. 2, 7 This makes maintaining the full therapeutic dose particularly important and safe in this population.

Common Pitfall to Avoid

Do not reduce acamprosate dosing in response to anxiety symptoms. The anxiety may actually improve with continued full-dose therapy combined with appropriate psychosocial interventions. 6, 5 Dose reduction risks treatment failure for alcohol dependence, which carries far greater morbidity and mortality than managing anxiety through appropriate adjunctive measures. 2