Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group.
BACKGROUND
Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors. These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD.


METHODS
A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD. Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d. Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable.


RESULTS
Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity.


CONCLUSIONS
Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.
Raskind
M A
MA
Veteran Affairs Puget Sound Health Care System and the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle 98108, USA.
Peskind
E R
ER
Wessel
T
T
Yuan
W
W
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D001835:Body Weight / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005702:Galantamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D016896:Treatment Outcome
D001057:Apolipoproteins E; D002800:Cholinesterase Inhibitors; D005702:Galantamine