Does memantine (N-methyl-D-aspartate receptor antagonist) need to be tapered when discontinuing?

Memantine Discontinuation: Tapering Recommendations

Memantine should be tapered when discontinuing rather than stopped abruptly to minimize potential discontinuation symptoms.

Evidence for Tapering Memantine

While the FDA label for memantine 1 does not explicitly mention a tapering requirement when discontinuing the medication, case reports and clinical evidence suggest that abrupt discontinuation can lead to adverse effects:

• Case reports document significant behavioral disturbances following abrupt cessation of memantine 2
• Discontinuation of memantine in nursing home residents with Alzheimer's disease has been associated with worsening health status, particularly affecting cognition and mood 3

Recommended Tapering Approach

Based on the available evidence, a gradual tapering approach is recommended:

1. Initial Assessment: Determine if deprescribing is appropriate (patient no longer benefiting, severe/end-stage dementia, or experiencing adverse effects) 4

2. Tapering Schedule:

   • Reduce dose by 5 mg increments (reverse of the titration schedule used when initiating therapy)
   • Allow at least one week between dose reductions
   • Example: 20 mg/day → 15 mg/day → 10 mg/day → 5 mg/day → discontinue

3. Monitoring During Taper:

   • Watch for emergence of behavioral disturbances or cognitive decline
   • If symptoms worsen significantly during tapering, consider returning to the previous dose and slowing the taper rate

Special Considerations

• Shared Decision Making: Engage patients and caregivers in the discontinuation process, explaining potential benefits and risks 4

• Monitoring After Discontinuation: Continue to monitor for at least 1-2 months after complete discontinuation to ensure no significant decline occurs

• Risk Factors for Difficult Discontinuation:

  • Long-term use of memantine
  • Higher doses (20 mg/day)
  • More advanced dementia

Common Pitfalls to Avoid

1. Abrupt Discontinuation: May lead to behavioral disturbances and cognitive decline 2

2. Mistaking Discontinuation Symptoms for Disease Progression: Withdrawal symptoms may be incorrectly attributed to worsening dementia rather than medication discontinuation

3. Inadequate Monitoring: Failing to follow up after discontinuation may miss important clinical changes

Practical Guidance

While specific guidelines for memantine tapering are less established than for other medications like benzodiazepines 5, applying principles from discontinuation of other CNS-active medications is reasonable. The tapering approach should be more cautious in patients who have been on memantine for longer periods or at higher doses.

If significant deterioration occurs during or after discontinuation, consider restarting memantine at the previous effective dose and attempting a more gradual taper in the future.