Donepezil Dosing for Alzheimer's Disease
The recommended dosing regimen for donepezil (Aricept) in Alzheimer's disease starts at 5 mg once daily in the evening, which can be increased to 10 mg once daily after 4-6 weeks if tolerated, with a maximum dose of 23 mg daily for moderate to severe disease after at least 3 months on 10 mg daily. 1
Initial Dosing and Titration
- Starting dose: 5 mg once daily in the evening, just prior to retiring
- Timing: Should be taken in the evening, can be taken with or without food
- Titration schedule:
- Maintain 5 mg daily for 4-6 weeks
- Increase to 10 mg daily if tolerated (for mild to moderate Alzheimer's)
- For moderate to severe Alzheimer's: May increase to 23 mg daily after at least 3 months on 10 mg daily
Dosing Based on Disease Severity
Mild to Moderate Alzheimer's Disease
- Starting dose: 5 mg once daily
- Maximum dose: 10 mg once daily
- Wait 4-6 weeks before increasing from 5 mg to 10 mg 2, 1
Moderate to Severe Alzheimer's Disease
- Starting dose: 5 mg once daily
- Intermediate dose: 10 mg once daily (after 4-6 weeks on 5 mg)
- Maximum dose: 23 mg once daily (after at least 3 months on 10 mg) 1
Administration Guidelines
- Take in the evening, just before bedtime
- Can be taken with or without food (taking with food may reduce gastrointestinal side effects)
- The 23 mg tablet should not be split, crushed, or chewed 1
Monitoring and Response Assessment
- Assess response after 6-12 months of treatment
- Beneficial response is determined by:
- Physician's global assessment
- Primary caregiver's report
- Neuropsychological assessment or mental status questionnaire
- Evidence of behavioral or functional changes 2
Side Effects Management
- Common side effects include nausea, vomiting, and diarrhea (dose-related)
- Side effects are typically mild and can be reduced by:
- Taking medication with food
- Gradual dose titration
- Initial increase in agitation may occur in some patients but typically subsides after a few weeks 2, 1
When to Discontinue
Discontinue donepezil if:
- Side effects develop and do not resolve
- Adherence is poor
- Deterioration continues at pre-treatment rate after 6-12 months of treatment 2
Common Pitfalls to Avoid
- Rapid dose escalation: Increasing the dose too quickly can lead to increased side effects
- Unrealistic expectations: Donepezil provides modest improvement or stabilization rather than dramatic improvement
- Inadequate trial duration: Brief mental status tests are relatively insensitive measures; observation for 6-12 months is usually necessary to assess benefit 2
- Ignoring non-responders: Patients who do not respond to one cholinesterase inhibitor may respond to another
Higher Dose Considerations
While the FDA-approved maximum dose is 23 mg for moderate to severe disease, research has shown that doses up to 20 mg/day appear safe and well-tolerated in patients already stabilized on donepezil 10 mg/day 3. However, higher doses are associated with increased incidence of cholinergic side effects, particularly gastrointestinal symptoms 1, 4.
Donepezil has demonstrated efficacy across the spectrum of Alzheimer's disease, with benefits potentially sustained for up to 18 months in patients who initially respond to treatment 5, 6.