| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Physostigmine Study Group.
The investigators and institutions of the Physostigmine Study Group are listed in the Appendix at the end of the article.
From the Department of Neurosciences (Dr. Thal), University of California San Diego and San Diego VAMC; Forest Laboratories, Inc. (Drs. Schwartz, Bodenheimer, and Schor), New York, NY; Columbia University, Sergievsky Center (Dr. Sano), New York, NY; University of Texas Southwestern Medical Center at Dallas (Dr. Weiner); Department of Neurology (Dr. Knopman), University of Minnesota Hospital; Department of Neurology VA and University of Alabama at Birmingham (Dr. Harrell); The National Hospital for Neurology and Neurosurgery (Dr. Rossor), London; Section of Old Age Psychiatry (Dr. Philpot), Institute of Psychiatry, Maudsley Hospital, London; and Pharmax Ltd. (Dr. Goldberg), Bexley, Kent, United Kingdom.
Supported by Forest Laboratories, Inc.
Received December 27, 1995. Accepted in final form May 9, 1996.
Address correspondence and reprint requests to Dr. Leon J. Thal, Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624.
Objective: A multicenter trial to evaluate the efficacy of controlled-release physostigmine salicylate, a cholinesterase inhibitor, was conducted in 1,111 mild-to-moderate Alzheimer's disease (AD) subjects. Design: During dose titration, subjects received 18, 24, or 30 mg of physostigmine or placebo daily. After a 2-week washout period, 366 subjects with putative improvement were randomized to receive either placebo or their best dose of physostigmine in a 6-week double-blind trial. Nonresponding patients (439) were randomized to receive in a separate double-blind trial either placebo or their highest tolerated dose of physostigmine. The primary efficacy measures included the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) and a Clinical Global Impression of Change (CGIC). Secondary measures included the Mini-Mental State Examination and two activities-of-daily-living scales. Results: At the end of the 6-week double-blind phase, physostigmine-treated patients scored 1.75 points higher than placebo-treated patients on the ADAS (p = 0.003) and 0.26 points higher on the CGIC (p = 0.012) in the intent-to-treat analysis. There was no significant improvement on the secondary outcome measures. Patients failing to respond to physostigmine during the dose titration phase failed to respond on any of the outcome measures during the double-blind period of re-exposure. Common adverse events included nausea, vomiting, diarrhea, and anorexia. There were no significant changes in liver function tests. Conclusion: This study demonstrated statistically significant differences between physostigmine and placebo on both a performance-based cognitive functioning instrument and a clinician's global evaluation. The magnitude of the effect size was small and occurred only in the subset of patients who responded in the initial dose titration study period. Nevertheless, the results suggest that in a subset of patients, physostigmine can induce a degree of cognitive improvement over 6 weeks of treatment.
NEUROLOGY 1996;47: 1389-1395
This article has been cited by other articles:
|
|
 |
|
  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.-H. Trinh, J. Hoblyn, S. Mohanty, and K. Yaffe Efficacy of Cholinesterase Inhibitors in the Treatment of Neuropsychiatric Symptoms and Functional Impairment in Alzheimer Disease: A Meta-analysis JAMA, January 8, 2003; 289(2): 210 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K Rockwood, J Mintzer, L Truyen, T Wessel, and D Wilkinson Effects of a flexible galantamine dose in Alzheimer's disease: a randomised, controlled trial J. Neurol. Neurosurg. Psychiatry, November 1, 2001; 71(5): 589 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Doody, J.C. Stevens, C. Beck, R.M. Dubinsky, J.A. Kaye, L. Gwyther, R.C. Mohs, L.J. Thal, P.J. Whitehouse, S.T. DeKosky, et al. Practice parameter: Management of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology, May 8, 2001; 56(9): 1154 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Doody, D. S. Geldmacher, B. Gordon, C. A. Perdomo, R. D. Pratt, and for the Donepezil Study Group Open-Label, Multicenter, Phase 3 Extension Study of the Safety and Efficacy of Donepezil in Patients With Alzheimer Disease Arch Neurol, March 1, 2001; 58(3): 427 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. van Dyck, P. Newhouse, W. E. Falk, J. A. Mattes, and for the Physostigmine Study Group Extended-Release Physostigmine in Alzheimer Disease: A Multicenter, Double-blind, 12-Week Study With Dose Enrichment Arch Gen Psychiatry, February 1, 2000; 57(2): 157 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Thal, M. Forrest, H. Loft, and H. Mengel Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease Neurology, January 25, 2000; 54(2): 421 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mayeux and M. Sano Treatment of Alzheimer's Disease N. Engl. J. Med., November 25, 1999; 341(22): 1670 - 1679. [Full Text] [PDF]
|
|
|
|
|
|
W. Pryse-Phillips Do We Have Drugs for Dementia?: No Arch Neurol, June 1, 1999; 56(6): 735 - 737. [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. McLendon and P. M. Doraiswamy Defining Meaningful Change in Alzheimer's Disease Trials: The Donepezil Experience J Geriatr Psychiatry Neurol, April 1, 1999; 12(1): 39 - 48. [Abstract] [PDF]
|
|
|
|
|
|
L. J. Thal, J. M. Ferguson, J. Mintzer, A. Raskin, and S. D. Targum A 24-week randomized trial of controlled-release physostigmine in patients with Alzheimer's disease Neurology, April 1, 1999; 52(6): 1146 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Farlow New Treatments in Alzheimer Disease and the Continued Need for Placebo-Controlled Trials Arch Neurol, November 1, 1998; 55(11): 1396 - 1398. [Full Text] [PDF]
|
|
|
|
|
|
D. Knopman, J. Kahn, and S. Miles Clinical Research Designs for Emerging Treatments for Alzheimer Disease: Moving Beyond Placebo-Controlled Trials Arch Neurol, November 1, 1998; 55(11): 1425 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Knopman and J. C. Morris An Update on Primary Drug Therapies for Alzheimer Disease Arch Neurol, November 1, 1997; 54(11): 1406 - 1409. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
