Objective: A comparison of the safety and tolerability of donepezil 5 and 10 mg/day in patients with vascular dementia (VaD) and patients with Alzheimer’s disease (AD) enrolled in randomized, double-blind, placebo-controlled clinical trials.
Background: Cholinesterase inhibitors, such as donepezil, are the cornerstone of therapy for AD, and donepezil is an effective and well-tolerated treatment in AD patients. Studies indicate that patients with VaD also benefit from treatment with donepezil; however, these patients have high levels of comorbid cardiovascular (CV) disease and are treated with numerous medications, so the tolerability profile of patients with VaD may differ from that of AD patients.
Design: Retrospective, exploratory analysis comparing the tolerability of donepezil in AD and VaD patients.
Materials and Methods: Incidences of adverse events (AEs) across placebo and donepezil 5 and 10 mg/day groups were compared using combined data from two 24-week, double-blind, placebo-controlled studies of donepezil in patients with probable or possible VaD (NINDS-AIREN criteria), and 10 similar studies in patients with probable AD (NINCDS-ADRDA criteria).
Results: 1219 VaD patients (placebo, n=392; donepezil 5 mg/day, n=406; donepezil 10 mg/day, n=421) and 2376 AD patients (placebo, n=893; donepezil 5 mg/day, n=821; donepezil 10 mg/day, n=662) were enrolled. Similar proportions of donepezil-treated and placebo-treated patients reported AEs, both in VaD (placebo, 88%; donepezil 5 mg/day, 90%; donepezil 10 mg/day, 93%), and in AD (placebo, 62%; donepezil 5 mg/day, 65%; donepezil 10 mg/day, 83%). The majority of AEs in both VaD and AD patients were of mild intensity. Withdrawals due to AEs were low, both in VaD (placebo, 10%; 5 mg/day, 11%; and donepezil 10 mg/day, 19%), and in AD (placebo, 6%; 5 mg/day, 6%; and donepezil 10 mg/day, 14%). The most commonly reported AEs in donepezil-treated VaD and AD patients (ie, nausea and diarrhea) were consistent with the cholinergic effect of donepezil. A higher proportion of VaD patients (90%) than AD patients (49%) had comorbid CV disease. The incidence of CV AEs was similar in donepezil- and placebo-treated VaD patients (placebo group, 20%; donepezil 5 mg/day, 20%; and donepezil 10 mg/day, 20%), and AD patients (placebo group, 7%; donepezil 5 mg/day, 7%; and donepezil 10 mg/day, 8%). In VaD patients, the proportion of patients with serious CV AEs in each treatment group was: placebo, 4%; donepezil 5 mg/day, 3%; and donepezil 10 mg/day, 6%.
Conclusion: VaD donepezil- and placebo-treated groups showed a higher incidence of AEs than corresponding AD groups, indicating that VaD patients are a more frail population than AD patients. Nevertheless, these results demonstrate that donepezil is well tolerated in VaD and AD patients.
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