What is the recommended treatment and dosage for mild to moderate Alzheimer's disease using Aricept (donepezil)?

Donepezil (Aricept) Treatment for Mild to Moderate Alzheimer's Disease

For mild to moderate Alzheimer's disease, donepezil should be initiated at 5 mg once daily in the evening, with an increase to 10 mg once daily after 4-6 weeks if well tolerated. 1, 2, 3

Dosing Recommendations

• Start with 5 mg donepezil once daily in the evening, just prior to retiring 1
• After 4-6 weeks, consider increasing to 10 mg once daily if the initial dose is well tolerated 1, 2
• Donepezil can be taken with or without food; taking with food may reduce gastrointestinal side effects 2, 3
• The maximum recommended dosage for mild to moderate Alzheimer's disease is 10 mg per day 1

Efficacy and Expected Benefits

• Donepezil produces clinically meaningful improvements in cognitive function and global clinical state in patients with mild to moderate Alzheimer's disease 2, 3
• Benefits include a statistically significant improvement in cognition (2-3 points on the ADAS-Cog scale) compared to placebo 4, 5
• Efficacy has been demonstrated for up to 4.9 years of treatment 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 3
• The 10 mg dose provides marginally greater benefits than the 5 mg dose, but with higher rates of adverse events 4

Monitoring Response

• Beneficial response should be assessed after 6-12 months of treatment 2
• Response is determined by physician's global assessment, caregiver reports, neuropsychologic assessments, or evidence of behavioral/functional changes 2
• Brief mental status tests alone are relatively insensitive measures of donepezil's cognitive effects 2
• Expect modest benefits (equivalent to delaying cognitive decline by approximately one year) 2

Side Effects and Management

• Common adverse effects include nausea, vomiting, diarrhea, and anorexia, which are dose-dependent and more common at 10 mg versus 5 mg 3, 5
• Some patients may experience an initial increase in agitation, which typically subsides after the first few weeks of therapy 2, 3
• Taking donepezil with food can help reduce gastrointestinal side effects 2, 6
• Consider discontinuing if side effects persist and don't resolve, if adherence is poor, or if deterioration continues at the pre-treatment rate after 6-12 months 2

Important Considerations and Pitfalls

• Communicate the expected modest benefits to patients and caregivers before initiating treatment 2
• Avoid starting at high doses, as gradual titration improves tolerability 3
• Administer in the evening rather than morning to minimize sleep disturbances 1
• Avoid expecting dramatic clinical improvement, as effects are statistically significant but modest in magnitude 3
• If a patient doesn't respond to donepezil, they may respond to another cholinesterase inhibitor 2
• Donepezil is not recommended for mild cognitive impairment as evidence shows no significant benefit 3

Alternative Dosing Considerations

• For moderate to severe Alzheimer's disease, dosing can be increased to 23 mg once daily, but only after patients have been on 10 mg daily for at least 3 months 1
• The 23 mg tablet should not be split, crushed, or chewed 1
• Studies show that benefits on 23 mg/day were no greater than on 10 mg/day, but with higher rates of adverse events 4