The Differential Effect of Galantamine in the Treatment of Dementia

Rafael Blesa, Neurology Department, Hospital Clinic, Neurology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain

Acetylcholinesterase inhibitors, such as galantamine (Reminyl) and donepezil (Aricept), are now widely accepted as effective treatment in Alzheimer’s disease (AD). Galantamine has consistently shown efficacy and tolerability in large-scale clinical trials in cognition, behavior, daily functioning and caregiver scales. Although donepezil and galantamine have many similarities in terms of their efficacy and tolerability, galantamine may offer additional benefits through its unique dual mode of action. Both agents inhibit acetylcholinesterase, thereby enhancing the synaptic availability of acetylcholine.

However, galantamine also sensitizes the nicotinic receptor, which is thought to play a key role in attention, memory and learning. In the first, long-term, head-to-head study of two active treatments in AD, donepezil and galantamine were compared on functional abilities and across a range of clinical domains in a rater-blind, randomized clinical trial over 1 year.

The study enrolled 182 patients with AD (Mini-Mental State Examination [MMSE] 9?18). The patients were randomized to receive flexible dosing with either galantamine 16 mg or 24 mg per day (n = 94, mean age 74.1 years, 56.4% females) or donepezil 5 mg or 10 mg per day (n = 88, mean age 72.8 years, 68.2% females) after a suitable period of titration. The primary endpoint was the Bristol Activities of Daily Living measure. A broad range of cognitive tests (MMSE and the Alzheimer's Disease Assessment Scale [ADAS-Cog]) were also performed.

Galantamine demonstrated an advantage compared to donepezil on cognition at weeks 13, 26 and 52 as measured by the MMSE. Patients treated with galantamine were, therefore, more likely to maintain or improve their current level of cognition. There were significantly higher responder rates for galantamine than donepezil on MMSE (55.3% vs. 34.5% in the intention-to-treat population and 58.0% vs 30.7% in the moderate MMSE population, respectively). Safety and tolerability were similar in both treatment groups. The data reinforces the clinical benefit of the dual action of galantamine.