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

Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE - Clin Interv Aging (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. rahansen@unc.edu

ABSTRACT
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.

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Comparative evidence for donepezil, galantamine, and rivastigminea.Notes: aLimited to comparisons with sufficient data for a single outcome measure and to doses recommended by product labeling.Abbreviations : WMD, Weighted Mean Difference (reflects the pooled difference for Drug A – Drug B); RR, Relative Risk (reflects the relative risk of responding with Drug B/Drug A); CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section; NPI, Neuropsychiatric Inventory; CIBIC+, Clinician Interview-Based Impression of Change Incorporating Caregiver Information.
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fig5: Comparative evidence for donepezil, galantamine, and rivastigminea.Notes: aLimited to comparisons with sufficient data for a single outcome measure and to doses recommended by product labeling.Abbreviations : WMD, Weighted Mean Difference (reflects the pooled difference for Drug A – Drug B); RR, Relative Risk (reflects the relative risk of responding with Drug B/Drug A); CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section; NPI, Neuropsychiatric Inventory; CIBIC+, Clinician Interview-Based Impression of Change Incorporating Caregiver Information.

Mentions: Two trials directly compared donepezil with galantamine (Wilcock et al 2003; Jones et al 2004), and two trials (4 articles) directly compared donepezil with rivastigmine (Wilkinson et al 2002; Bullock et al 2005, 2006; Touchon et al 2006). Only one of the four comparative trials was double-blinded (Bullock et al 2005). Relevant outcome data are shown in Figure 5.


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

Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE - Clin Interv Aging (2008)

Comparative evidence for donepezil, galantamine, and rivastigminea.Notes: aLimited to comparisons with sufficient data for a single outcome measure and to doses recommended by product labeling.Abbreviations : WMD, Weighted Mean Difference (reflects the pooled difference for Drug A – Drug B); RR, Relative Risk (reflects the relative risk of responding with Drug B/Drug A); CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section; NPI, Neuropsychiatric Inventory; CIBIC+, Clinician Interview-Based Impression of Change Incorporating Caregiver Information.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2546466&req=5

fig5: Comparative evidence for donepezil, galantamine, and rivastigminea.Notes: aLimited to comparisons with sufficient data for a single outcome measure and to doses recommended by product labeling.Abbreviations : WMD, Weighted Mean Difference (reflects the pooled difference for Drug A – Drug B); RR, Relative Risk (reflects the relative risk of responding with Drug B/Drug A); CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section; NPI, Neuropsychiatric Inventory; CIBIC+, Clinician Interview-Based Impression of Change Incorporating Caregiver Information.
Mentions: Two trials directly compared donepezil with galantamine (Wilcock et al 2003; Jones et al 2004), and two trials (4 articles) directly compared donepezil with rivastigmine (Wilkinson et al 2002; Bullock et al 2005, 2006; Touchon et al 2006). Only one of the four comparative trials was double-blinded (Bullock et al 2005). Relevant outcome data are shown in Figure 5.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. rahansen@unc.edu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus