What is the recommended dosing regimen for donepezil (Aricept) in a geriatric patient with mild to moderate Alzheimer's disease?

Donepezil Dosing for Alzheimer's Disease

Start donepezil at 5 mg once daily in the evening, just prior to retiring, and increase to 10 mg once daily after 4-6 weeks if well tolerated. 1, 2, 3

Standard Dosing Algorithm for Mild to Moderate Alzheimer's Disease

• Initial dose: 5 mg once daily in the evening before bedtime for all patients with mild to moderate Alzheimer's disease 1, 2, 3
• Titration: Increase to 10 mg once daily after 4-6 weeks if the patient tolerates the initial dose without significant adverse effects 1, 2, 3
• Timing: Always administer in the evening just prior to retiring to minimize sleep disturbances 1
• Food: Can be taken with or without food, though taking with food may reduce gastrointestinal side effects 1, 3

The 4-6 week titration period is critical because donepezil has a 70-hour half-life, requiring adequate time to reach steady-state concentrations before dose escalation 1. The FDA label explicitly states that 10 mg should not be administered until patients have been on 5 mg daily for 4-6 weeks 3.

Dosing for Moderate to Severe Alzheimer's Disease

• Start with the same 5 mg daily regimen, then escalate to 10 mg after 4-6 weeks 3
• Consider 23 mg once daily for patients who have been stable on 10 mg for at least 3 months and continue to decline 3, 4
• The 23 mg tablet must be swallowed whole—do not split, crush, or chew 3

The higher 23 mg dose provides additional benefits in moderate to severe AD, particularly for language and visuospatial ability, though it carries increased risk of gastrointestinal side effects 4.

Expected Clinical Benefits and Timeline

• Cognitive improvements appear within 3 weeks to 3 months of initiating treatment 5, 6
• The 10 mg dose provides superior cognitive and functional benefits compared to 5 mg, demonstrating a clear dose-response relationship 1, 7
• Benefits are maintained for approximately 21-81 weeks with the 10 mg daily dose 1, 6
• Average improvements are modest (not reaching the 4-point ADAS-cog change considered clinically significant), but a subset of patients will achieve clinically meaningful improvement 1

Managing Side Effects

• Relative risk of gastrointestinal effects at 10 mg vs 5 mg: nausea/vomiting (2.54×), diarrhea (2.57×), and anorexia (3.21×) 1
• Minimize side effects by:
  • Taking donepezil with food 1
  • Using gradual titration over 4-6 weeks rather than rapid escalation 1, 6
  • Administering at bedtime rather than morning 1
• Most adverse events are mild, transient, and cholinergic in nature (gastrointestinal and nervous system effects) 6, 7

The 7-day dose escalation schedules used in early trials resulted in higher adverse event rates; the current 4-6 week titration minimizes these effects 6.

Critical Contraindications and Precautions

• Do NOT prescribe donepezil for mild cognitive impairment—evidence shows no significant benefit in this population 1
• Contraindicated in patients with known hypersensitivity to donepezil or piperidine derivatives 3
• Use caution in patients with:
  • Cardiac conduction abnormalities (may cause bradycardia or heart block) 3
  • Planned anesthesia (exaggerates succinylcholine-type muscle relaxation) 3

Assessment and Continuation Criteria

• Allow 6-12 months to adequately assess treatment benefit before considering discontinuation 2
• Discontinue if:
  • Persistent side effects that cannot be managed 2
  • Continued deterioration at the pre-treatment rate despite optimal dosing 2
• Brief mental status tests (like MMSE) are relatively insensitive measures—use comprehensive assessments including caregiver reports and functional evaluations 2

Common Pitfalls to Avoid

• Avoid premature discontinuation—some patients require up to 12 months to demonstrate benefit 2
• Avoid inadequate titration—the 10 mg dose is more effective than 5 mg for most patients 1, 7
• Avoid unrealistic expectations—counsel patients and caregivers that treatment slows decline rather than reversing it 2
• Do not escalate to 10 mg before 4-6 weeks on 5 mg—this increases adverse event rates without allowing adequate assessment of tolerability 3, 6