Treatment effects between monotherapy of donepezil versus combination with memantine for Alzheimer disease: A meta-analysis.

Ruey Chen,Pi-Chen Chang,Kuei-Ru Chou,Hsin Chu,Chien-Yu Chen,Pi-Tuan Chan,Yu-Cih Lin,Kewei Chen

doi:10.1371/journal.pone.0183586

Abstract

BackgroundThis is the first meta-analysis to compare the treatment effects and safety of administering donepezil alone versus a combination of memantine and donepezil to treat patients with moderate to severe Alzheimer Disease, particularly regarding cognitive functions, behavioral and psychological symptoms in dementia (BPSD), and global functions.MethodsPubMed, Medline, Embase, PsycINFO, and Cochrane databases were used to search for English and non-English articles for inclusion in the meta-analysis to evaluate the effect size and incidence of adverse drug reactions of different treatments.ResultsCompared with patients who received donepezil alone, those who received donepezil in combination with memantine exhibited limited improvements in cognitive functions (g = 0.378, p < .001), BPSD (g = −0.878, p < .001) and global functions (g = −0.585, p = .004). Gradual titration of memantine plus a fixed dose and gradual titration of donepezil as well as a fixed dose and gradual titration of memantine resulted in limited improvements in cognitive functions(g = 0.371, p = .005), BPSD(g = −0.913, p = .001), and global functions(g = −0.371, p = .001).ConclusionBoth in the 24th week and at the final evaluation point, the combination of donepezil and memantine led to greater improvement in cognitive functions, BPSD, and global functions than did donepezil alone in patients with moderate to severe Alzheimer Disease.

Highlights

Alzheimer disease (AD) is the most prevalent type of dementia, accounting for more than 80% of cases of dementia in middle- and senior-aged patients. [1] Current treatment strategies primarily focus on medications and are aimed at alleviating symptoms
Gradual titration of memantine plus a fixed dose and gradual titration of donepezil as well as a fixed dose and gradual titration of memantine resulted in limited improvements in cognitive functions(g = 0.371, p = .005), behavioral and psychological symptoms in dementia (BPSD)(g = −0.913, p = .001), and global functions(g = −0.371, p = .001)
Cholinesterase inhibitors (ChEIs) and N-methyl D-aspartate (NMDA) receptor antagonists are the two most prevalent types of medicine approved by the U.S Food and Drug Administration

Summary

Introduction

Alzheimer disease (AD) is the most prevalent type of dementia, accounting for more than 80% of cases of dementia in middle- and senior-aged patients. [1] Current treatment strategies primarily focus on medications and are aimed at alleviating symptoms. [4,5,6] Despite the wealth of information on the ChEIs and memantine for treating AD, the magnitude of the effects of administering of donepezil and a combination of memantine and donepezil on patients’ cognitive functions, BPSD, and global functions remains unclear This is the first meta-analysis to compare the effects of administering donepezil alone versus combination of memantine and donepezil for treating patients with moderate to severe AD. We aimed to carry out a scientific and precise meta-analysis with extensive searches from multiple databases to examine: 1) the effect size; 2) moderator analysis; 3) subgroup analysis; and 4) the quality and publication bias on the effect of outcome variables This is the first meta-analysis to compare the treatment effects and safety of administering donepezil alone versus a combination of memantine and donepezil to treat patients with moderate to severe Alzheimer Disease, regarding cognitive functions, behavioral and psychological symptoms in dementia (BPSD), and global functions

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