Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease.
OBJECTIVE
To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD).


BACKGROUND
Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (AChE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD.


METHODS
A multicentre, randomized, parallel, double-blind, placebo-controlled trial was carried out to evaluate the efficacy and tolerability of galantamine 18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to-moderate probable AD. The primary outcome measure was the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration Scale (PDS).


RESULTS
Patients treated with galantamine 24 mg/day had a significantly better outcome than placebo on ADAS-cog; the treatment difference was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points on per protocol analysis ( p = 0.001). Per protocol analysis showed that galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well tolerated at the lower doses of 18 and 24 mg/day where it produced mild, transient effects typical of cholinomimetic agents.


CONCLUSIONS
This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease.
Wilkinson
D
D
Old Age Psychiatry, Thornhill Research Unit, Moorgreen Hospital, Southampton, UK. dwilk2000@aol.com
Murray
J
J
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003072:Cognition Disorders / Q000209:etiology*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005702:Galantamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D005702:Galantamine