Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease

Objectives To investigate whether Galantamine significantly improves the core symptoms of Alzheimer's disease (AD) Background Galantamine is a reversible, competitive, selective inhibitor of acetylcholinesterase (ACNE) that also allosterically modulates nicotinic acetylcholine receptors. This dual mechanism of action provided the rationale for a phase II trial of galantamine in AD. Method 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. Conclusion This study shows that, relative to placebo, galantamine significantly improves the core symptoms of Alzheimer's disease. Copyright (C) 2001 John Wiley & Sons, Ltd.