Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis

Abstract

Richard A Hansen1, Gerald Gartlehner2, Aaron P Webb1, Laura C Morgan3, Charity G Moore4, Daniel E Jonas31School of Pharmacy, 3Cecil G Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, NC, USA; 2Department for Evidence-based Medicine and Clinical Epidemiology, Danube University, Krems, Austria; 4Center for Research on Health Care Data Center; University of Pittsburgh, Pittsburgh, PA, USAAbstract: Pharmacologic treatments for Alzheimer’s disease include the cholinesterase inhibitors donepezil, galantamine, and rivastigmine. We reviewed their evidence by searching MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 through 2007 (July) for placebo-controlled and comparative trials assessing cognition, function, behavior, global change, and safety. Thirty-three articles on 26 studies were included in the review. Meta-analyses of placebo-controlled data support the drugs’ modest overall benefits for stabilizing or slowing decline in cognition, function, behavior, and clinical global change. Three open-label trials and one double-blind randomized trial directly compared donepezil with galantamine and rivastigmine. Results are conflicting; two studies suggest no differences in efficacy between compared drugs, while one study found donepezil to be more efficacious than galantamine, and one study found rivastigmine to be more efficacious than donepezil. Adjusted indirect comparison of placebo-controlled data did not find statistically significant differences among drugs with regard to cognition, but found the relative risk of global response to be better with donepezil and rivastigmine compared with galantamine (relative risk = 1.63 and 1.42, respectively). Indirect comparisons also favored donepezil over galantamine with regard to behavior. Across trials, the incidence of adverse events was generally lowest for donepezil and highest for rivastigmine.Keywords: Alzheimer’s disease, cholinesterase inhibitor, donepezil, galantamine, rivastigmine, systematic review, meta-analysis, indirect comparison