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(Stroke. 2003;34:2323.)
© 2003 American Heart Association, Inc.

Original Contributions

Efficacy and Tolerability of Donepezil in Vascular Dementia

Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial

Sandra Black, FRCPC; Gustavo C. Román, MD, FACP, FRSM(Lond); David S. Geldmacher, MD; Stephen Salloway, MD; Jane Hecker, MD; Alistair Burns, MD; Carlos Perdomo, MS; Dinesh Kumar, MS Raymond Pratt, MD and the Donepezil 307 Vascular Dementia Study Group

From the University of Toronto, Department of Medicine (Division of Neurology), Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada (S.B.); University of Texas Health Sciences Center at San Antonio and Veterans Administration Hospital, San Antonio, Tex (G.C.R.); Memory Disorders Program, Department of Neurology, University of Virginia, Charlottesville (D.S.G.); Butler Hospital, Brown Medical School, Providence, RI (S.S.); Department of Rehabilitation and Aged Care, Repatriation General Hospital, Daw Park, South Australia, Australia (J.H.); University of Manchester and Wythenshawe Hospital, Manchester, UK (A.B.); and Eisai Inc, Teaneck, NJ (C.P., D.K., R.P.).

Correspondence to Raymond Pratt, Eisai Inc, Glenpointe Centre West, Teaneck, NJ 07666-6741. E-mail ray_pratt{at}eisai.com

Background and Purpose— 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.

Key Words: dementia • donepezil • randomized controlled trials

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