Galantamine in Alzheimer's
Disease:
A
6-month randomized, placebo-controlled trial with a 6-month extension. The
Galantamine USA-1 Study Group.
Raskind MA, Peskind ER, Wessel T, Yuan W.
Veteran Affairs Puget Sound Health Care System and the Department of Psychiatry
and Behavioral Sciences, University of Washington, Seattle 98108, USA.
Abstract
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 Alzheimer's Disease (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.
