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From the Division of Neurology (Dr. Feldman), UBC Hospital, Clinic for Alzheimer’s Disease and Related Disorders, Vancouver, BC; Alzheimer Disease Research Unit (Dr. Gauthier), McGill Centre for Studies in Aging, Verdun, QC, Canada; Department of Rehabilitation and Aged Care (Dr. Hecker), Repatriation General Hospital, Daw Park, SA, Australia; Toulouse University Alzheimer’s Center (Dr. Vellas), France; and Pfizer Pharmaceuticals Group (Dr. Subbiah) and Biometrics Department, Pfizer Pharmaceuticals Group (Dr. Whalen), Pfizer Pharmaceuticals Inc., New York, NY.
Address correspondence and reprint requests to Dr. H. Feldman, Division of Neurology, UBC Hospital, S192-2211 Wesbrook Mall, Vancouver, BC V6T2B5, Canada; e-mail: hfeldman{at}interchange.ubc.ca
Objective:— To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score 
6 at baseline).
Methods:— Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician’s judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+).
Results:— Patients’ mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean ± SE sMMSE scores at baseline were 11.7 ± 0.35 for the donepezil group and 12.0 ± 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary measures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated patients completed the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of placebo-treated patients, the majority of which were rated mild in severity; 8% of donepezil- and 6% of placebo-treated patients discontinued because of AE. Laboratory and vital sign abnormalities were similar between the treatment groups.
Conclusion:— These data suggest that donepezil’s benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.
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 |
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 A. Qaseem, V. Snow, J. T. Cross Jr., M. A. Forciea, R. Hopkins Jr., P. Shekelle, A. Adelman, D. Mehr, K. Schellhase, D. Campos-Outcalt, et al. Current Pharmacologic Treatment of Dementia: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians Ann Intern Med, March 4, 2008; 148(5): 370 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 G. A. Marshall, L. Monserratt, D. Harwood, M. Mandelkern, J. L. Cummings, and D. L. Sultzer Positron Emission Tomography Metabolic Correlates of Apathy in Alzheimer Disease Arch Neurol, July 1, 2007; 64(7): 1015 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Rowland, J. Rigby, A. C. Harper, and R. Rowland Cardiovascular monitoring with acetylcholinesterase inhibitors: a clinical protocol Adv. Psychiatr. Treat., May 1, 2007; 13(3): 178 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Chiappelli, A. M. Navarro, D. R. Moradi, E. Manfrini, and P. Prolo Evidence-Based Research in Complementary and Alternative Medicine III: Treatment of Patients with Alzheimer's Disease Evid. Based Complement. Altern. Med., December 1, 2006; 3(4): 411 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Burns and J. O'Brien Clinical practice with anti-dementia drugs: a consensus statement from British Association for Psychopharmacology J Psychopharmacol, November 1, 2006; 20(6): 732 - 755. [Abstract] [PDF]
|
|
|
|
 |
|
 J. M Ringman Donepezil improves cognitive function and reduces decline in activities of daily living in people with severe Alzheimer's disease. Evid. Based Ment. Health, November 1, 2006; 9(4): 104 - 104. [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Farlow Use of Antidementia Agents in Vascular Dementia: Beyond Alzheimer Disease Mayo Clin. Proc., October 1, 2006; 81(10): 1350 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 H. Kaduszkiewicz, T. Zimmermann, H.-P. Beck-Bornholdt, and H. van den Bussche Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials BMJ, August 6, 2005; 331(7512): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 K. M. Sink, K. F. Holden, and K. Yaffe Pharmacological Treatment of Neuropsychiatric Symptoms of Dementia: A Review of the Evidence JAMA, February 2, 2005; 293(5): 596 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D Chiaravalloti, J. DeLuca, N. B Moore, and J. H Ricker Treating learning impairments improves memory performance in multiple sclerosis: a randomized clinical trial Multiple Sclerosis, February 1, 2005; 11(1): 58 - 68. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Zhang, F.-M. Zhou, and J. A. Dani Cholinergic Drugs for Alzheimer's Disease Enhance in Vitro Dopamine Release Mol. Pharmacol., September 1, 2004; 66(3): 538 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
N. Herrmann and D. Knopman Donepezil therapy for neuropsychiatric symptoms in AD: Methods make the message Neurology, July 27, 2004; 63(2): 200 - 201. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
K Rockwood Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, May 1, 2004; 75(5): 677 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yasui-Furukori, H. Furukori, A. Kaneda, S. Kaneko, and T. Tateishi The Effects of Ginkgo biloba Extracts on the Pharmacokinetics and Pharmacodynamics of Donepezil J. Clin. Pharmacol., May 1, 2004; 44(5): 538 - 542. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. L. Cummings Use of Cholinesterase Inhibitors in Clinical Practice: Evidence-Based Recommendations Focus, April 1, 2004; 2(2): 239 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 J. Mintzer and S. D. Targum Psychosis in Elderly Patients: Classification and Pharmacotherapy J Geriatr Psychiatry Neurol, December 1, 2003; 16(4): 199 - 206. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Black, G. C. Roman, D. S. Geldmacher, S. Salloway, J. Hecker, A. Burns, C. Perdomo, D. Kumar, and R. Pratt Efficacy and Tolerability of Donepezil in Vascular Dementia: Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial Stroke, October 1, 2003; 34(10): 2323 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 F. J. Kier and V. Molinari "Do-It-Yourself" Dementia Testing: Issues Regarding an Alzheimer's Home Screening Test Gerontologist, June 1, 2003; 43(3): 295 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Porter, W. G. Buxton, L. A. Fairbanks, T. Strickland, S. M. O'Connor, S. Rosenberg-Thompson, and J. L. Cummings Frequency and Characteristics of Anxiety Among Patients With Alzheimer's Disease and Related Dementias J Neuropsychiatry Clin Neurosci, May 1, 2003; 15(2): 180 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
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|
 G. T. Grossberg and A. K. Desai Management of Alzheimer's Disease J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2003; 58(4): M331 - 353. [Full Text] [PDF]
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|
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 Drugs for disruptive features in dementia DTB, January 1, 2003; 41(1): 1 - 4. [Abstract] [Full Text] [PDF]
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|
|
 |
|
 S. J. Bartels, A. R. Dums, T. E. Oxman, L. S. Schneider, P. A. Arean, G. S. Alexopoulos, and D. V. Jeste Evidence-Based Practices in Geriatric Mental Health Care Psychiatr Serv, November 1, 2002; 53(11): 1419 - 1431. [Abstract] [Full Text] [PDF]
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I. T. Lott, K. Osann, E. Doran, and L. Nelson Down Syndrome and Alzheimer Disease: Response to Donepezil Arch Neurol, July 1, 2002; 59(7): 1133 - 1136. [Abstract] [Full Text] [PDF]
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 D. Wilkinson Review: haloperidol does not reduce agitation in dementia Evid. Based Med., May 1, 2002; 7(3): 89 - 89. [Full Text] [PDF]
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Other Articles Noted Evid. Based Ment. Health, May 1, 2002; 5(2): 40 - 40. [Full Text] [PDF]
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ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB Evid. Based Med., March 1, 2002; 7(2): 35 - 35. [Full Text] [PDF]
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S. Gauthier Advances in the pharmacotherapy of Alzheimer's disease Can. Med. Assoc. J., March 1, 2002; 166(5): 616 - 623. [Full Text] [PDF]
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 Donepezil in Moderate-to-Severe Alzheimer's Disease Journal Watch Psychiatry, October 18, 2001; 2001(1018): 13 - 13. [Full Text]
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 Donepezil in Moderate-to-Severe Alzheimer's Disease Journal Watch (General), September 11, 2001; 2001(911): 1 - 1. [Full Text]
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