Memantine vs Donepezil for Dementia

Efficacy and Safety

The American College of Physicians recommends donepezil for mild to moderate Alzheimer's disease, with a mean improvement of -2.67 points on the ADAS-cog scale and 1.05 points on MMSE at 24-26 weeks, according to the Annals of Internal Medicine 2, 3
Memantine demonstrates significant benefits on the SIB cognitive scale and CIBIC-plus global assessment in moderate to severe Alzheimer's disease, with a mean difference of 5.92 points on the SIB scale 1
The American Geriatrics Society suggests memantine shows stronger evidence in vascular dementia, with significant improvements on ADAS-cog, and should be considered first-line 1
Donepezil has a higher risk of gastrointestinal side effects, including nausea, diarrhea, and anorexia, with a relative risk of 2.54, 2.57, and 3.21, respectively 5
Memantine has a more favorable side effect profile, with no statistically significant increases in most adverse events compared to placebo, and may actually reduce agitation 1, 7

The American Academy of Neurology recommends starting donepezil at 5 mg daily and increasing to 10 mg after 4-6 weeks if tolerated, and administering it in the morning to minimize sleep disturbances 6
For moderate to severe Alzheimer's disease, memantine can be added to donepezil, with a starting dose of 5 mg daily and titrated gradually to 20 mg daily 1

While both drugs show statistically significant benefits, the average improvements do not reach clinically meaningful thresholds, with an average ADAS-cog improvement of -2.67 points and MMSE improvement of 1.05 points 2, 3