Donepezil: Acetylcholinesterase Inhibitor for Alzheimer's Disease
Donepezil (Aricept) is a selective, reversible acetylcholinesterase (AChE) inhibitor used for symptomatic treatment of Alzheimer's disease (AD). It enhances cholinergic neurotransmission by preventing acetylcholine breakdown.
First-line symptomatic treatment for all stages of AD (mild, moderate, and severe). Does not halt disease progression but slows cognitive decline. Also used off-label in vascular dementia and Lewy body dementia.
Mechanism of Action
Reversibly inhibits acetylcholinesterase in the synaptic cleft, increasing acetylcholine availability. This compensates for cholinergic neuron loss in AD. Does not modify the underlying amyloid or tau pathology.
Indications & Use
Mild-to-moderate and severe Alzheimer's disease. Off-label: vascular dementia, Lewy body dementia, Parkinson's disease dementia (though rivastigmine is more commonly preferred here).
Dosage
Start 5 mg once daily at bedtime. After 4–6 weeks, increase to 10 mg/day if tolerated. In severe AD, 23 mg/day (special formulation) may be used. Administer at bedtime to reduce GI side effects and use sleep time for drug metabolism.
Side Effects
Common: nausea, vomiting, diarrhoea, muscle cramps, insomnia, vivid dreams. Mostly GI and cholinergic — often resolve in 1–2 weeks. Bradycardia (vagotonic effect) — caution in patients with cardiac conduction disorders.
Drug Interactions
Anticholinergics: pharmacodynamic antagonism — avoid (urinary incontinence medications, antihistamines, TCAs). NSAIDs/aspirin: increased GI bleeding risk. Beta-blockers: additive bradycardia. CYP3A4/CYP2D6 inducers reduce levels.
Contraindications
Hypersensitivity to piperidine derivatives. Caution in sick sinus syndrome, conduction defects (bradycardia risk), active peptic ulcer, asthma/COPD (may worsen), seizure history.
Frequently Asked Questions
Does donepezil cure Alzheimer's?
No. Donepezil is symptomatic — it compensates for acetylcholine loss but does not stop the underlying neurodegeneration. It can slow functional decline by 6–12 months in some patients.
Why is donepezil taken at night?
Taken at bedtime, GI side effects (nausea, diarrhoea) occur during sleep when less noticed. Also, the drug is metabolised during the night, providing stable daytime levels.
How long should donepezil be continued?
Continue as long as the patient benefits and tolerates it. Even in severe AD, evidence supports continuation. Stopping abruptly can cause rapid functional decline — taper if discontinuing.
References
- NICE NG97: Dementia 2018 (updated 2023)
- EMA Aricept SPC 2023
- Birks JS, Harvey RJ. Cochrane Review 2018
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.