| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Neurosciences (Dr. Thal), University of California San Diego School of Medicine, La Jolla, CA; the Pharmacology Research Corporation (Dr. Ferguson), Salt Lake City, UT; the Medical University of South Carolina (Dr. Mintzer), Charleston, SC; the Valley Village Professional Center (Dr. Raskin), Pasadena, MD; and Crozer-Chester Medical Center (Dr. Targum), Upland, PA.
Address correspondence and reprint requests to Dr. Leon J. Thal, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0624.
OBJECTIVE: To evaluate the safety and efficacy of controlled-release physostigmine, an acetylcholinesterase inhibitor, in patients with probable AD of mild to moderate severity.
METHODS: A prospective, 24-week, randomized, multicenter, double-blind, parallel group study of patients was conducted. The study enrolled 475 patients at 24 sites. Patients met criteria for probable AD and were randomized to one of three arms: placebo, controlled-release (CR) physostigmine 30 mg daily, or CR physostigmine 36 mg daily. Dosage was escalated by a forced upward titration during the first 6 to 9 weeks of the trial, then maintained at a constant dose to 24 weeks. Primary outcome measures were the Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) and the Clinician’s Interview-Based Impression of Change–Plus with caregiver input (CIBIC+). Secondary outcome measures included the Clinical Global Impression of Change (CGIC), the Geriatric Evaluation by Relatives Rating Instrument, and an Instrumental Activities of Daily Living Scale.
RESULTS: In an intent-to-treat population, the last observation carried forward analysis revealed a 2.9-point ADAS-Cog (p = 0.002) difference between physostigmine and placebo-treated patients for both dosages, and a 0.26 to 0.31-point difference on the CIBIC+ (p = 0.048). There were no significant differences on the secondary outcome measures except for a difference on the CGIC when analyzed by use of the Cochran–Mantel–Haenszel statistic (p = 0.014). There were significant increases in gastrointestinal side effects including nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain for patients on either dose of physostigmine, resulting in a high dropout rate. Agitation was decreased significantly. There was no evidence of cardiac rhythm disturbance or liver function abnormalities.
CONCLUSION: CR physostigmine enhanced cognitive and global function. It is relatively safe for the treatment of cognitive dysfunction secondary to AD. However, in light of the gastrointestinal side effects, a lower starting dose and a flexible titration schedule might lead to a more favorable adverse event profile in the clinical arena.
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]
|
|
|
|
|
|
O L Lopez, J T Becker, S Wisniewski, J Saxton, D I Kaufer, and S T DeKosky Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, March 1, 2002; 72(3): 310 - 314. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 R. Mayeux and M. Sano Treatment of Alzheimer's Disease N. Engl. J. Med., November 25, 1999; 341(22): 1670 - 1679. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
