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From the Department of Psychiatry (Dr. Tariot), University of Rochester Medical Center, NY; Department of Psychology (Dr. Solomon), Williams College, MA, and the Memory Clinic, Southwestern Vermont Medical Center, Bennington, VT; Department of Neurology (Dr. Morris), Washington University School of Medicine, St. Louis, MO; the Janssen Research Foundation (Drs. Kershaw and Ding), Titusville, NJ; and the Janssen Research Foundation (Dr. Lilienfeld), Beerse, Belgium.
Address correspondence and reprint requests to Dr. Pierre N. Tariot, Department of Psychiatry, Monroe Community Hospital, 435 East Henrietta Road, Rochester, NY 14620.
OBJECTIVE: To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD.
METHODS: A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out.
RESULTS: After 5 months, the galantamine–placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild.
CONCLUSIONS: Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events.
Key words: AD—Galantamine—Allosteric modulation—Nicotinic receptors—Acetylcholinesterase inhibition—Randomized controlled trial—Efficacy—Dose escalation—Tolerability.
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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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|
|
|
|
 |
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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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|
|
|
|
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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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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 R Vandenberghe and J Tournoy Cognitive aging and Alzheimer's disease Postgrad. Med. J., June 1, 2005; 81(956): 343 - 352. [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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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 S. Kavanagh and P. Kabathova Drug therapy for Alzheimer's disease Can. Med. Assoc. J., April 27, 2004; 170(9): 1371 - 1372. [Full Text] [PDF]
|
|
|
|
 |
|
 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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|
|
|
|
 |
|
 M. A. Raskind, E. R. Peskind, L. Truyen, P. Kershaw, and C. V. Damaraju The Cognitive Benefits of Galantamine Are Sustained for at Least 36 Months: A Long-term Extension Trial Arch Neurol, February 1, 2004; 61(2): 252 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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|
|
|
|
 |
|
 C. H. Kawas Early Alzheimer's Disease N. Engl. J. Med., September 11, 2003; 349(11): 1056 - 1063. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
J. L. Cummings Use of Cholinesterase Inhibitors in Clinical Practice: Evidence-Based Recommendations Am J Geriatr Psychiatry, April 1, 2003; 11(2): 131 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
C. M. Clark and J. H.T. Karlawish Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies Ann Intern Med, March 4, 2003; 138(5): 400 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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]
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