Donepezil Dosing for Dementia
Start donepezil at 5 mg once daily in the evening, then increase to 10 mg once daily after 4-6 weeks if the medication is well tolerated. 1
Initial Dosing Strategy
- Begin with 5 mg once daily taken in the evening just prior to retiring, regardless of whether the patient has mild, moderate, or severe Alzheimer's disease 1
- The medication can be taken with or without food 1
- This starting dose applies to all patients with dementia of the Alzheimer's type 1
Dose Escalation Timeline
- Wait 4-6 weeks before increasing from 5 mg to 10 mg daily 1, 2
- This waiting period is critical because it minimizes gastrointestinal side effects (nausea, diarrhea, vomiting) that are dose-related and more common when escalation occurs too rapidly 3, 1
- The longer titration period (6 weeks rather than 7 days) significantly reduces the incidence of cholinergic adverse events 4
Target Maintenance Dose
- 10 mg once daily is the standard maintenance dose for mild to moderate Alzheimer's disease 1, 2
- For moderate to severe disease, 10 mg daily remains appropriate, though 23 mg daily may be considered after at least 3 months on 10 mg 1, 5
- Evidence shows that 10 mg provides superior cognitive and functional benefits compared to 5 mg 3, 4
Evidence Supporting This Approach
The FDA-approved dosing is supported by extensive clinical trial data showing that both 5 mg and 10 mg doses improve cognition and global function in Alzheimer's disease and vascular dementia 3. The 10 mg dose demonstrates clinically significant changes on global assessment measures (CIBIC-plus), though effects on cognitive scales (ADAS-cog) are statistically significant but smaller 3. The gradual titration schedule balances efficacy with tolerability, as adverse events are primarily gastrointestinal and dose-related 3, 1.
Assessment Period
- Allow 6-12 months to adequately assess treatment benefit before considering discontinuation 2
- Beneficial effects on cognition typically appear within 3 months, but comprehensive assessment requires longer observation 2
- Use physician global assessment, caregiver reports, and functional/behavioral changes rather than relying solely on brief mental status tests 2
Common Pitfalls to Avoid
- Do not escalate too quickly: Increasing from 5 mg to 10 mg before 4 weeks significantly increases gastrointestinal side effects 1, 4
- Do not discontinue prematurely: Most gastrointestinal side effects are mild, transient, and can be minimized by taking the medication with food 2, 4
- Do not split, crush, or chew tablets, particularly the 23 mg formulation if prescribed 1