Donepezil in vascular dementia: combined analysis of two large-scale clinical trials.
OBJECTIVE
There are currently no drugs approved to treat vascular dementia (VaD). The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients.


METHODS
Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE)], global function [Clinician's Interview-Based Impression of Change plus (CIBIC-plus), Clinical Dementia Rating-Sum of the Boxes (CDR-SB)] and function [Alzheimer's Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS-IADL)].


RESULTS
Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p < 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p < 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events.


CONCLUSIONS
This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD.
Román
Gustavo C
GC
Department of Medicine (Neurology), University of Texas Health Science Center and Audie Murphy Veterans Hospital, San Antonio, Tex. 78229-3900, USA. romang@uthsca.edu
Wilkinson
David G
DG
Doody
Rachelle S
RS
Black
Sandra E
SE
Salloway
Stephen P
SP
Schindler
Rachel J
RJ
D000203:Activities of Daily Living; D000368:Aged; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002985:Clinical Protocols; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D000077265:Donepezil; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil