Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.
OBJECTIVE
Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD.


METHODS
Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population.


RESULTS
At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo).


CONCLUSIONS
These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.
Black
Sandra
S
University of Toronto, Department of Medicine (Division of Neurology), Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Román
Gustavo C
GC
Geldmacher
David S
DS
Salloway
Stephen
S
Hecker
Jane
J
Burns
Alistair
A
Perdomo
Carlos
C
Kumar
Dinesh
D
Pratt
Raymond
R
D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D002319:Cardiovascular System / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D015140:Dementia, Vascular / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D038622:Internationality; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil