Donepezil — Aricept — is the most prescribed cholinesterase inhibitor. The half-life is long (~70 hours), enabling once-daily dosing, and the FDA approvals span mild, moderate, and severe Alzheimer's disease. For a population that often struggles with medication adherence, the simplicity of once-daily is meaningful.
- Class
- Acetylcholinesterase inhibitor
- Mechanism
- Selective reversible AChE inhibition (vs butyrylcholinesterase)
- Typical dose
- 5 mg daily for 4-6 weeks, then 10 mg daily; 23 mg for severe disease (higher GI burden)
- Half-life
- ~70 hours
- FDA indications
- Mild, moderate, and severe Alzheimer's disease
- Key adverse effects
- GI (nausea, vomiting, diarrhea, anorexia), insomnia/vivid dreams (if AM dosed — switch to bedtime), bradycardia, syncope, muscle cramps
Long half-life allows once-daily dosing. Most prescribed AChEI. FDA approval spans mild to severe disease (broader than rivastigmine, galantamine). Bedtime dosing reduces dream disturbances; AM dosing if causing daytime sedation.
Dosing: start 5 milligrams daily for 4-6 weeks, then increase to 10 milligrams. The 23-milligram formulation is approved for severe disease — extending use into later stages, though with higher GI burden and modest additional cognitive benefit over 10 milligrams.
Dosing timing matters and varies by patient. Bedtime dosing reduces vivid dreams and nightmares for some patients but worsens sleep onset for others. Morning dosing avoids the sleep concerns but may produce sedation or fatigue during the day. The right time is patient-specific — start with bedtime, adjust if dreams or sleep problems emerge.
Side effects share the AChEI class profile. GI is most common: nausea, diarrhea, vomiting, anorexia. Slow titration mitigates. Take with food. Monitor weight. Vivid dreams, sleep disturbance, bradycardia, syncope, urinary incontinence, muscle cramps round out the profile.
Donepezil is the most-prescribed cholinesterase inhibitor — once-daily, broadly indicated, with a tolerability profile shaped by its cholinergic mechanism.
Mechanism note: Donepezil's once-daily dosing and broad stage approval make it the default cholinesterase inhibitor; manage the cholinergic GI and sleep effects with titration and timing.
For mild-to-moderate Alzheimer's, donepezil is often the AChEI of first choice. Once-daily dosing wins on adherence; the long track record gives families confidence. For severe disease, the 23-milligram formulation can extend use. For most situations, this is the AChEI you reach for first.
- Cost
- Generic: ~$10-30/month.
- Generic status
- Generic since 2010.
- Formulary typical
- Tier 1 generic.
- Access friction
- None for most patients. 23 mg formulation has had access concerns historically.
Prescriber tip: Cheap and accessible workhorse AChEI. For severe disease 23 mg formulation, document mild-to-moderate failure for PA if needed.