Safety and efficacy of galantamine (Reminyl) in severe Alzheimer's disease (the SERAD study): a randomised, placebo-controlled, double-blind trial

Lancet Neurol. 2009 Jan;8(1):39-47. doi: 10.1016/S1474-4422(08)70261-8. Epub 2008 Nov 29.


Background: The efficacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its efficacy in patients with severe AD.

Methods: Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5-12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary efficacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with, number NCT00216593.

Findings: 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1.9 (95% CI -0.1 to 3.9) points with galantamine and decreased (worsened) by 3.0 (-5.6 to -0.5) points with placebo (between-group least squares mean difference 4.36, 1.3 to 7.5; p=0.006). Mean MDS-ADL self-performance score worsened by 1.2 (0.6 to 1.8) points and 1.6 (0.8 to 2.3) points, respectively (between-group least squares mean difference -0.41, -1.3 to 0.5; p=0.383). Nominally significant between-group differences in favour of galantamine occurred for the SIB domains of memory (p=0.006), praxis (p=0.010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0.021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups.

Interpretation: Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to significantly improve the co-primary parameter of overall activities of daily living.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / mortality
  • Alzheimer Disease / psychology
  • Cognition / physiology
  • Double-Blind Method
  • Electrocardiography / drug effects
  • Female
  • Galantamine / adverse effects
  • Galantamine / therapeutic use*
  • Humans
  • Male
  • Neuropsychological Tests
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*


  • Nootropic Agents
  • Galantamine

Associated data