Donepezil: a clinical review of current and emerging indications.
This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.
Román
Gustavo C
GC
Medicine/Neurology, Mail Code 7883, University of Texas HSC, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. romang@uthscsa.edu
Rogers
Susan J
SJ
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy; D015140:Dementia, Vascular / Q000188:drug therapy / Q000523:psychology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011950:Receptors, Cholinergic / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011950:Receptors, Cholinergic; D000077265:Donepezil