Donepezil (E-2020) is a reversible, noncompetitive,
piperidine-type
cholinesterase inhibitor. It is selective for
acetylcholinesterase rather than
butyrylcholinesterase.
Donepezil 5 and 10 mg/day significantly improved cognition and global clinical function compared with placebo in well designed short term trials (14 to 30 weeks) in 161 to 818 patients with mild to moderate
Alzheimer's disease. Beneficial effects on cognition were observed from week 3 of treatment.
Donepezil 10 mg/day significantly delayed the deterioration in
activities of daily living (
ADL) [by 55 weeks] compared with placebo in a retrospective analysis of 1 trial, and in the largest trial significantly improved patients' abilities to perform complex tasks. However, no significant improvement in function was observed with
donepezil 5 mg/day in another trial. In the 2 trials of longest duration
donepezil (5 and 10 mg) significantly delayed symptomatic progression of the disease. While there was no evidence for a positive effect of
donepezil on patients' quality of life, there are no validated measures of this parameter specific to patients with
Alzheimer's disease.
Donepezil (5 and 10 mg) significantly reduced caregiver burden. Long term efficacy data suggest that improvements in cognition, global function or
ADL are maintained for about 21 to 81 weeks with
donepezil (10 mg/day in most patients).
Donepezil is generally well tolerated with the majority of adverse events being mild and transient. Predictably, most events were
cholinergic in nature and generally related to the gastrointestinal and nervous systems. The incidence of these events was significantly higher with
donepezil 10 mg than with placebo in short term clinical trials; however, this may have been due to the 7-day dose increase schedule used in these studies and can be minimised by increasing the dose after a longer (6-week) period. The incidence of serious adverse events was generally similar between
donepezil 5 and 10 mg (4 to 10%) and placebo (5 to 9%) in short term trials. 26% of patients receiving
donepezil (5 and 10 mg) reported serious events over a 98-week period in a long term trial. Importantly, there was no evidence of hepatotoxicity with this
drug. Conclusions.
Donepezil (5 and 10 mg) is an agent with a simple once-daily dosage schedule which improves cognition and global clinical function in the short (up to 24 weeks) and long term (up to about 1 year) in patients with mild to moderate
Alzheimer's disease. Improvements in
ADL were also observed with
donepezil 10 mg/day. Adverse events associated with
donepezil are mainly
cholinergic.
Donepezil has been extensively studied and should be considered as a first-line treatment in patients with mild to moderate
Alzheimer's disease.