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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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Meta-analysis of cognitive outcomes (ADAS-cog) for active treatment compared with placebo.Notes: aLimited to doses recommended by product labeling.Abbreviations: WMD, Weighted Mean Difference; PRC, Prolonged Release Capsule; CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section.
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fig1: Meta-analysis of cognitive outcomes (ADAS-cog) for active treatment compared with placebo.Notes: aLimited to doses recommended by product labeling.Abbreviations: WMD, Weighted Mean Difference; PRC, Prolonged Release Capsule; CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section.

Mentions: Fourteen studies measured and reported the mean change in ADAS-cog score from baseline to endpoint for active treatment compared with placebo; five on donepezil (Rogers and Friedhoff 1996; Rogers et al 1998a, 1998b; Homma et al 2000; Seltzer et al 2004); seven on galantamine (Raskind et al 2000; Tariot et al 2000; Wilcock et al 2000; Rockwood et al 2001, 2006; Wilkinson and Murray 2001; Brodaty et al 2005); and two on rivastigmine (Corey-Bloom et al 1998; Rosler et al 1999). All of these studies lasted 3 to 6 months and included participants with mild to moderate dementia (except for one which included only participants with mild dementia; see Seltzer et al 2004). Across studies, the average age of participants was 74 years (range 69 to 78 years), and 62% were female (range 50% to 69% female). Limiting these studies to doses recommended in the manufacturers labeling (Figure 1), the pooled weighted mean difference in change between active treatment and placebo was −2.67 (95% confidence interval [CI] −3.28 to −2.06) for donepezil, −2.76 (95% CI −3.17 to −2.34) for galantamine, and −3.01 (95% CI −3.80 to −2.21) for rivastigmine. The I2 statistic—which reflects the degree of heterogeneity among pooled studies—was 0% for both donepezil and galantamine, but 70% for rivastigmine (reflecting high heterogeneity for the two pooled studies). Pooled estimates were not statistically significantly different when analyses were stratified by dose (data not shown).


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)

Meta-analysis of cognitive outcomes (ADAS-cog) for active treatment compared with placebo.Notes: aLimited to doses recommended by product labeling.Abbreviations: WMD, Weighted Mean Difference; PRC, Prolonged Release Capsule; CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Meta-analysis of cognitive outcomes (ADAS-cog) for active treatment compared with placebo.Notes: aLimited to doses recommended by product labeling.Abbreviations: WMD, Weighted Mean Difference; PRC, Prolonged Release Capsule; CI, Confidence Interval; ADAS-cog, Alzheimer’s Disease Assessment Scale-Cognitive section.
Mentions: Fourteen studies measured and reported the mean change in ADAS-cog score from baseline to endpoint for active treatment compared with placebo; five on donepezil (Rogers and Friedhoff 1996; Rogers et al 1998a, 1998b; Homma et al 2000; Seltzer et al 2004); seven on galantamine (Raskind et al 2000; Tariot et al 2000; Wilcock et al 2000; Rockwood et al 2001, 2006; Wilkinson and Murray 2001; Brodaty et al 2005); and two on rivastigmine (Corey-Bloom et al 1998; Rosler et al 1999). All of these studies lasted 3 to 6 months and included participants with mild to moderate dementia (except for one which included only participants with mild dementia; see Seltzer et al 2004). Across studies, the average age of participants was 74 years (range 69 to 78 years), and 62% were female (range 50% to 69% female). Limiting these studies to doses recommended in the manufacturers labeling (Figure 1), the pooled weighted mean difference in change between active treatment and placebo was −2.67 (95% confidence interval [CI] −3.28 to −2.06) for donepezil, −2.76 (95% CI −3.17 to −2.34) for galantamine, and −3.01 (95% CI −3.80 to −2.21) for rivastigmine. The I2 statistic—which reflects the degree of heterogeneity among pooled studies—was 0% for both donepezil and galantamine, but 70% for rivastigmine (reflecting high heterogeneity for the two pooled studies). Pooled estimates were not statistically significantly different when analyses were stratified by dose (data not shown).

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