Donepezil as First-Line Treatment for Alzheimer's Disease

Introduction to Donepezil Treatment

The American Academy of Family Physicians recommends starting donepezil 5 mg once daily in the evening for patients with newly diagnosed Alzheimer's disease, with efficacy maintained for up to 4.9 years 1
Donepezil demonstrates clinically meaningful improvements in cognition and global function, with approximately 20-35% of patients showing a 7-point improvement on neuropsychologic tests, equivalent to reversing one year's decline 1
Taking donepezil with food reduces gastrointestinal side effects, such as nausea, vomiting, and diarrhea, and initial agitation may occur but typically subsides after the first few weeks 1

For mild to moderate Alzheimer's disease, the American Academy of Family Physicians recommends starting donepezil 5 mg once daily in the evening, with an increase to 10 mg daily after 4-6 weeks if tolerated, and donepezil has been shown to have efficacy maintained for up to 4.9 years 1
For moderate to severe Alzheimer's disease, the guideline society recommends initiating treatment with donepezil first, using the same dosing schedule, and then adding memantine after establishing donepezil therapy, with combination therapy showing superior outcomes compared to cholinesterase inhibitor monotherapy 2

Memantine should be considered as add-on therapy to donepezil in moderate to severe disease for enhanced cognitive and functional benefits, particularly when neuropsychiatric symptoms are prominent, according to the American College of Physicians 2
Memantine may be used as monotherapy only if cholinesterase inhibitors are contraindicated or not tolerated, as stated by the American College of Physicians 3

Donepezil is not hepatotoxic, unlike tacrine, and has a mild and transient side effect profile, primarily cholinergic, according to the American Academy of Family Physicians 1