Summary of Donepezil(Aricept®) in Treating Alzheimer's Disease

 

WHAT IT IS

Aricept (donepezil) is a cholinesterase inhibitor. It doesn’t cure Alzheimer’s or stop the disease, but it can boost the brain’s chemical messenger (acetylcholine) to ease symptoms for a period of time. It’s approved for mild, moderate, and severe Alzheimer’s disease. 

 

 

 

HOW WELL IT WORKS

Benefits are modest but real for many people—most noticeable in thinking/memory tests, daily activities, and a clinician’s overall impression. Effects are typically measured over 6–12 months; they tend to slow decline more than create big improvements.

 

 

WHO BENEFTIS MOST

Evidence is strongest in mild–to–moderate stages, with measurable but still modest gains; benefits in very mild disease are smaller. 

 

 

 

DOSE MATTERS

Both 5 mg and 10 mg daily improve cognition, with 10 mg showing a bit more benefit for some patients. (Doctors often start at 5 mg for a month, then increase if tolerated.)

 

 

COMBINATION THERAPY

Some analyses suggest adding memantine in later stages can give slightly better overall outcomes than either medicine alone. Your clinician may consider this if symptoms progress. 

 

 

GUIDELINE STANCE

Major guidelines continue to recommend cholinesterase inhibitors like donepezil for Alzheimer’s; they shouldn’t be stopped solely because the disease has become severe if the person still seems to benefit and tolerates the drug. 

 

 

SAFETY AND SIDE EFFECTS

Most people tolerate Aricept fairly well. Common, usually mild effects include nausea, diarrhea, decreased appetite/weight loss, insomnia/vivid dreams, and muscle cramps (often easing after the first weeks or when taken with food or at night).

 

It’s fairly common for people on cholinesterase inhibitort to lose some weight—about 1 out of every 20 patients loses 10 pounds or more in the first year. (11) For others, smaller losses (a few pounds) are more typical. Because unintentional weight loss can weaken muscles and increase frailty, doctors usually recommend regular weigh-ins (every month or two at first). If someone is already thin or frail, this side effect deserves close watching.

 

Aricept can slow the heart rate and cause fainting in susceptible people—especially those with existing heart-rhythm problems or on certain heart/blood-pressure medicines. Clinicians may check pulse, blood pressure, EKG history, and falls risk. Recent safety reviews suggest no increase in dangerous arrhythmias overall, but vigilance is still advised in at-risk patients.

 

 

MONITOR SIDE EFFECTS AND FALL RISK

Report dizziness, fainting, new slow pulse, weight loss, stomach upset, or sleep problems promptly.  Don’t stop abruptly: If benefit is seen and side effects are manageable, guidelines support continuing, even in more advanced stages, with periodic re-evaluation.

 

 
PRACTICAL TAKEAWAYS & TIPS

 

 

Donepezil is helpful for symptoms, not disease-modifying. Keep expectations realistic. The evidence shows modest small day-to-day gains: a bit more clarity, smoother conversations, better orientation, or staying independent a little longer with dressing, eating, or managing a routine. Not everyone notices changes, but slower worsening is common even when clear improvement isn’t. 

 

The 5 mg and 10 mg doses are standard; 10 mg/day tends to give somewhat better cognitive results than 5 mg/day, albeit with higher risk of side effects. 

 

Give it time: It can take weeks to a few months to judge if it works for you. Benefits tend to be measured over 6–24 weeks (and sometimes longer in observational follow-up).

 

Note: There is no conclusive evidence that donepezil (alone or with memantine) dramatically alters long-term disease progression; gains are symptomatic and transient. The long-term data come from open-label or extension studies — which lack placebo controls and thus are subject to bias. 

 

Add-on of memantine to donepezil is used in practice for moderate–severe disease — but controlled data do not consistently show a big advantage over donepezil alone (for primary outcomes).

 

Donepezil is generally tolerated; common side-effects (especially cholinergic: gastrointestinal, etc.) are well documented. Higher doses (e.g. 23 mg/day) may increase side-effect risk, weight loss, and withdrawal rate — so dose escalation should be balanced against tolerability. 

 

Regular check-ins for pulse, falls, and weight are the safest way to get the benefits while minimizing risks. 

 

Combining Aricept with good sleep, activity, diet, social engagement, and, in some cases, memantine, may offer added benefit as part of a whole-person plan.

References

1. Birks, J. S., & Harvey, R. J. (2018). Donepezil for people with dementia due to Alzheimer’s disease. Cochrane Database of Systematic Reviews, (6), CD001190. https://doi.org/10.1002/14651858.CD001190.pub3

2. Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., & Friedhoff, L. T. (1998). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology, 50(1), 136–145. https://doi.org/10.1212/WNL.50.1.136

3. Aricept Study Group. (2000). Efficacy and safety of donepezil in patients with Alzheimer’s disease: A randomized, double-blind, placebo-controlled trial. Neurology, 54(1), 205–213.

4. Wilkinson, D., & Murray, J. (2001). The efficacy and tolerability of donepezil in patients with Alzheimer’s disease. Journal of Clinical Practice, 55(8), 600–604.

5. Farlow, M. R., Salloway, S., Tariot, P. N., Yardley, J., Moline, M. L., Wang, Q., Brand-Schieber, E., & Zou, H. (2010). Effectiveness and tolerability of high-dose (23 mg/day) versus standard-dose (10 mg/day) donepezil in moderate to severe Alzheimer’s disease: A 24-week, randomized, double-blind trial. BMC Neurology, 11, 57. https://doi.org/10.1186/1471-2377-11-576. 

6. Matsunaga, S., Kishi, T., & Iwata, N. (2015). Memantine monotherapy for Alzheimer's disease: A systematic review and meta-analysis. PLoS ONE, 10(4), e0123289. (Useful for comparison with combination therapy.)

7. Kavirajan, H., & Schneider, L. S. (2011). Efficacy and safety of memantine in moderate-to-severe Alzheimer’s disease: The evidence to date. Drugs & Aging, 28(1), 37–47. (Reviews combination therapy with donepezil.)

8. Howard, R., McShane, R., Lindesay, J., Ritchie, C., Baldwin, A., Barber, R., ... & Phillips, P. (2012). Donepezil and memantine for moderate-to-severe Alzheimer’s disease. New England Journal of Medicine, 366(10), 893–903. https://doi.org/10.1056/NEJMoa1106668

9. Haider, F., Ahmed, M. E., & Ali, A. (2024). Efficacy and safety of donepezil 5 mg/day versus 10 mg/day in Alzheimer’s disease: A systematic review and meta-analysis. Frontiers in Neuroscience, 18, 1398952. https://doi.org/10.3389/fnins.2024.1398952

10. Winblad, B., Kilander, L., Eriksson, S., Minthon, L., Båtsman, S., Näslund, J., & Reines, S. (2006). Donepezil in Alzheimer's disease: A randomized, double-blind study in 144-week extension. Archives of Neurology, 63(6), 785–792. https://doi.org/10.1001/archneur.63.6.785

11. Sheffrin M, Miao Y, Boscardin WJ, Steinman MA. Weight Loss Associated with Cholinesterase Inhibitors in Individuals with Dementia in a National Healthcare System. J Am Geriatr Soc. 2015;63(8):1512-1518. doi:10.1111/jgs.13511