Aricept (Donepezil) Treatment Regimen for Mild to Moderate Alzheimer's Disease
Initial Dosing
Start donepezil at 5 mg once daily in the evening, just prior to retiring, for patients with mild to moderate Alzheimer's disease. 1, 2, 3
- The FDA-approved starting dose is 5 mg once daily for mild to moderate disease 3
- Evening administration is specifically recommended to minimize sleep disturbances that can occur with morning dosing 1
- This initial dose allows assessment of tolerability before escalation 2
Dose Escalation
Increase to 10 mg once daily after 4-6 weeks if the initial dose is well tolerated. 1, 2
- The American Academy of Family Physicians recommends waiting 4-6 weeks before dose escalation 1
- Some protocols suggest a minimum of 4 weeks at the lower dose 2
- The 10 mg dose provides additional cognitive and functional benefits over 5 mg 2, 4
- Gradual titration significantly improves tolerability and minimizes gastrointestinal side effects 1, 2
Expected Clinical Benefits
Donepezil produces statistically significant but modest improvements in cognition and global function, though these do not typically reach the 4-point change in ADAS-cog considered clinically significant. 2, 4
- High-quality evidence demonstrates consistent treatment effects across all severity levels of Alzheimer's disease except mild cognitive impairment 2
- Benefits on cognitive function, activities of daily living, and behavior can be maintained for approximately 21 to 81 weeks with donepezil 10 mg/day 2, 5
- In clinical trials, the mean drug-placebo differences were 2.5-3.1 units on ADAS-cog and 0.3-0.4 units on CIBIC-plus 4
- Beneficial effects on cognition are typically observed from week 3 of treatment 5
Side Effect Management
Monitor closely for dose-dependent gastrointestinal side effects, particularly during the first few weeks after initiation or dose increase. 1, 2
- The relative risk of nausea/vomiting at 10 mg vs 5 mg is 2.54 1, 2
- The relative risk of diarrhea at 10 mg vs 5 mg is 2.57 1, 2
- The relative risk of anorexia at 10 mg vs 5 mg is 3.21 1, 2
- These effects can be minimized by taking donepezil with food and using gradual titration 1
- Initial increase in agitation may occur but typically subsides after the first few weeks 2
Critical Pitfalls to Avoid
Do not prescribe donepezil for mild cognitive impairment, as evidence shows no significant benefit in this population. 2
- Avoid starting at high doses without gradual titration, as this significantly increases gastrointestinal side effects 2
- Do not administer donepezil in the morning rather than evening, as this increases the risk of sleep disturbances 1, 2
- Avoid setting unrealistic expectations for dramatic clinical improvement, as effects are statistically significant but modest in magnitude 2
- Monitor for bradycardia or heart block, as cholinesterase inhibitors may have vagotonic effects on cardiac conduction 3
- Observe patients closely for gastrointestinal bleeding, especially those at increased risk for developing ulcers 3