| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Division of Neurology (S.E.B.), Department of Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada; Alzheimer's Disease and Memory Disorders Center (R.D.), Baylor College of Medicine, Houston, TX; Eisai Inc. (H.L., Y.S., S.R.), Teaneck, NJ; Worldwide Neurosciences, Pfizer Global Pharmaceuticals (T.M.), Pfizer Inc. (Y.X.), New York, NY; PPSI (K.M.J.), Stamford, CT; and Biostatistics (C.A.P.), Eisai Medical Research Inc., Ridgefield Park, NJ.
Address correspondence and reprint requests to Dr. Sandra Black, LC Campbell Cognitive Neurology Research Unit, Sunnybrook Health Sciences Centre, Room A421, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada sandra.black{at}sunnybrook.ca
Objective: To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD).
Methods: Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores 
6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving 1 dose of donepezil or placebo.
Results: Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD.
Conclusion: Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.
Supplemental data at www.neurology.org
Supported by Eisai Inc. and Pfizer Inc.
Disclosure: Sandra Black, MD, reports receiving contract research grants not reported in this article in excess of $10,000 per year and receiving honoraria for ad hoc consulting and CME in excess of $10,000 per year during the course of the study. Rachelle Doody, MD, reports receiving contract research grants not reported in this article in excess of $10,000 per year. Honglan Li, PhD, reports being a current employee of the sponsor. Thomas McRae, MD, reports being a current employee of the sponsor. Kyle Marie Jambor, MA, reports being funded by the sponsors to provide editorial support in the preparation of the manuscript. Yikang Xu, PhD, reports having equity or ownership interest in the sponsor in excess of $10,000 per year and is a current employee of the sponsor. Yijun Sun, PhD, reports being a current employee of the sponsor. Carlos Perdomo, MS, reports being a current employee of the sponsor. Sharon Richardson, PhD, reports being a current employee of the sponsor.
Received September 16, 2006. Accepted in final form March 2, 2007.
This article has been cited by other articles:
|
|
 |
|
  B. Winblad Review: Donepezil in Severe Alzheimer's Disease American Journal of Alzheimer's Disease and Other Dementias, June 1, 2009; 24(3): 185 - 192. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Smith Treatment of Alzheimer's disease in the long-term-care setting Am. J. Health Syst. Pharm., May 15, 2009; 66(10): 899 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Doody, S. H. Ferris, S. Salloway, Y. Sun, R. Goldman, W. E. Watkins, Y. Xu, and A. K. Murthy Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial Neurology, May 5, 2009; 72(18): 1555 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Remington, A. Chan, J. Paskavitz, and T. B. Shea Efficacy of a Vitamin/Nutriceutical Formulation for Moderate-stage to Later-stage Alzheimer's disease: A Placebo-controlled Pilot Study American Journal of Alzheimer's Disease and Other Dementias, February 1, 2009; 24(1): 27 - 33. [Abstract] [PDF]
|
|
|
|
 |
|
 S. SALLOWAY and S. CORREIA Alzheimer disease: Time to improve its diagnosis and treatment Cleveland Clinic Journal of Medicine, January 1, 2009; 76(1): 49 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Herrmann MD and S. Gauthier MD Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease Can. Med. Assoc. J., December 2, 2008; 179(12): 1279 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Cholinesterase Inhibitors for Dementia More Studies, Similar Results Journal Watch (General), August 9, 2007; 2007(809): 5 - 5. [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
