Discontinuation of Donepezil and Memantine: Taper Required
Both donepezil and memantine should be tapered gradually rather than discontinued abruptly, with dose reductions of 50% every 4 weeks until reaching the starting dose, followed by 4 weeks at the starting dose before complete discontinuation. 1
Tapering Protocol
The 5th Canadian Consensus Conference on Dementia provides explicit guidance on deprescribing these medications:
- Reduce the dose by 50% every 4 weeks until the initial starting dose is reached 1
- Maintain the starting dose for 4 weeks before complete discontinuation 1
- Monitor closely for clinically meaningful worsening of cognition, functioning, neuropsychiatric symptoms, or global assessment 1
- Reinitiate treatment immediately if deterioration appears related to medication cessation 1
Evidence Supporting Gradual Discontinuation
Abrupt discontinuation carries significant risks:
- Sudden withdrawal of donepezil produces acute cognitive and behavioral decline in patients with dementia with Lewy bodies and Parkinson's disease dementia 2
- Abrupt cessation of memantine can result in discontinuation syndrome with significant behavioral disturbance 3
- Discontinuing cholinesterase inhibitors results in worse cognitive function (mean difference of -2.09 SMMSE points at 12 months) and greater functional impairment (mean difference of -3.38 BADLS points at 12 months) compared to continuation 4, 5
Special Circumstances Requiring Caution
Do NOT discontinue cholinesterase inhibitors in patients with:
- Active clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms stabilize (unless the symptoms were worsened by the medication itself) 1
- History of clinically meaningful reduction in neuropsychiatric symptoms (especially psychosis) with cognitive enhancers, even if cognitive and functional decline is evident 1
When Discontinuation Should Be Considered
Discontinuation is appropriate after gradual tapering when:
- Clinically meaningful worsening of dementia over 6 months without other contributing medical or environmental factors 1
- No clinically meaningful benefit observed at any time during treatment 1
- Severe or end-stage dementia with dependence in most basic activities of daily living 1
- Development of intolerable side effects (nausea, vomiting, weight loss, anorexia, falls for donepezil; confusion, dizziness, falls for memantine) 1
- Poor medication adherence precluding safe ongoing use 1
Common Pitfall to Avoid
Never abruptly discontinue these medications. The FDA label for donepezil does not provide specific discontinuation guidance 6, but clinical evidence demonstrates that abrupt cessation causes deterioration that may not be fully reversible even after restarting treatment 3, 2. The gradual tapering protocol minimizes withdrawal effects and allows for early detection of medication-related benefits that may have been underappreciated during continuous treatment 1.