When to Start Donepezil or Memantine for Dementia
Donepezil should be initiated in mild to moderate Alzheimer's disease, while memantine is most beneficial in moderate to severe Alzheimer's disease, with combination therapy recommended for moderate to severe cases. 1
Donepezil (Aricept) Initiation Guidelines
Mild to Moderate Alzheimer's Disease
- Donepezil is indicated for mild to moderate Alzheimer's disease, showing statistically significant improvement in cognition and global function compared to placebo 1
- Start with 5mg once daily in the morning (not at bedtime) to minimize sleep disturbances 2
- After 4 weeks, consider increasing to 10mg daily if well tolerated 3
- Donepezil shows consistent treatment effects for improvement in cognitive function across all severity levels of Alzheimer's disease except mild cognitive impairment 1
Vascular Dementia
- Donepezil also shows significant benefits in vascular dementia, though effects are smaller than in Alzheimer's disease 1
- Treatment should be initiated at the same dosing schedule as for Alzheimer's disease 4
Not Recommended For
- Mild cognitive impairment - donepezil showed no significant benefit in this population (p=0.31) 1
- While short-term reduction in conversion to Alzheimer's disease was observed, differences disappeared by 36 months 1
Memantine (Namenda) Initiation Guidelines
Moderate to Severe Alzheimer's Disease
- Memantine is primarily indicated for moderate to severe Alzheimer's disease (MMSE scores ≥3 and ≤14) 5
- Start at 5mg once daily and increase weekly by 5mg/day in divided doses to a target dose of 20mg/day (10mg twice daily) 5
- Memantine demonstrated statistically significant benefits in activities of daily living (ADL) scores and cognitive function in moderate to severe Alzheimer's disease 5
Combination Therapy
- For patients with moderate to severe Alzheimer's disease already on donepezil for at least 6 months, adding memantine provides additional benefits 5, 6
- Combination therapy shows superior outcomes in cognitive function, activities of daily living, and global clinical state compared to donepezil monotherapy 5, 6
Monitoring and Expectations
Expected Benefits
- For donepezil: Improvements in cognition appear within 3 weeks of treatment initiation 7
- Benefits on cognitive function, activities of daily living, and behavior can be maintained for approximately 21 to 81 weeks with donepezil 10mg/day 7
- Neither medication achieves the 4-point change in ADAS-cog considered clinically significant, though statistically significant improvements occur 1
Side Effect Management
- Monitor for gastrointestinal side effects with donepezil, particularly:
- Nausea and vomiting (relative risk 2.54)
- Diarrhea (relative risk 2.57)
- Anorexia (relative risk 3.21)
- These are dose-dependent and more common at 10mg versus 5mg 3
- Initial increase in agitation may occur with donepezil but typically subsides after the first few weeks 3
Common Pitfalls to Avoid
- Prescribing donepezil for mild cognitive impairment - evidence shows no significant benefit 1
- Starting at high doses - gradual titration improves tolerability 3
- Administering donepezil at bedtime rather than morning - increases risk of sleep disturbances 2
- Delaying memantine addition in moderate to severe disease - combination therapy shows superior outcomes to monotherapy 5, 6
- Expecting dramatic clinical improvement - effects are statistically significant but modest in magnitude 1, 8