First-Line Starting Dose for Alzheimer's Medication
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, 4
Initial Dosing Protocol
The FDA-approved and guideline-recommended starting dose is 5 mg once daily, taken in the evening before bedtime. 1, 2, 3, 4
The dose should be increased to 10 mg once daily after 4-6 weeks if the patient tolerates the initial dose well. 1, 3, 4
Donepezil can be taken with or without food, though taking it with food may minimize gastrointestinal side effects. 1
The medication should be administered at bedtime rather than in the morning to reduce sleep disturbances. 1
Rationale for This Dosing Strategy
The 5 mg starting dose balances efficacy with tolerability, as adverse events are dose-dependent and significantly more common at higher doses. 1, 2
Gradual titration from 5 mg to 10 mg after 4-6 weeks allows assessment of tolerability before escalating, which improves treatment adherence. 1, 3, 4
The 10 mg dose provides superior cognitive and functional benefits compared to 5 mg, but the initial lower dose minimizes early discontinuation due to side effects. 1
Donepezil has a 70-hour half-life, making once-daily dosing appropriate and allowing steady-state concentrations to be achieved before dose escalation. 1
Expected Outcomes and Timeline
Beneficial effects on cognition are typically observed within 3 months of treatment initiation. 2, 3
Statistically significant improvements occur in cognitive function (ADAS-Cog), global clinical state, and activities of daily living, though average improvements are modest. 1, 2
Benefits can be maintained for approximately 21-81 weeks with the 10 mg daily dose. 1, 2
An assessment period of 6-12 months is necessary to adequately evaluate treatment response. 3
Side Effect Management
The most common adverse events are gastrointestinal: nausea/vomiting (relative risk 2.54 at 10 mg vs 5 mg), diarrhea (relative risk 2.57), and anorexia (relative risk 3.21). 1, 2
These effects can be minimized by taking donepezil with food and using gradual dose titration over 4-6 weeks rather than rapid escalation. 1, 3
Initial agitation may occur but typically subsides after the first few weeks of treatment. 2
Monitor for cardiovascular effects including bradycardia, as cholinesterase inhibitors have vagotonic effects on cardiac conduction. 4
Common Pitfalls to Avoid
Do not prescribe donepezil for mild cognitive impairment, as evidence shows no significant benefit in this population. 1, 2
Do not start at 10 mg daily, as this increases the risk of adverse events and early treatment discontinuation. 1, 3, 4
Do not escalate to 10 mg before 4 weeks of treatment, as insufficient time at the lower dose increases gastrointestinal side effects. 1, 3, 4
Do not administer in the morning, as this timing increases sleep disturbances compared to evening dosing. 1, 2
Do not expect dramatic clinical improvement, as effects are statistically significant but modest in magnitude—realistic expectations should be discussed before initiating treatment. 2, 3