Efficacy of Memantine, Donepezil, or Their Association in Moderate-Severe Alzheimer’s Disease: A Review of Clinical Trials

Ivana Molino,Luisa Colucci,Francesco Amenta,Angiola M Fasanaro,Enea Traini

doi:10.1155/2013/925702

Abstract

Background. Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage. Objectives. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD. Method. Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007–2012. Results and Conclusion. Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of “adequacy and representativeness.” Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.

Highlights

Alzheimer’s disease (AD), the most common adult-onset dementia, is associated with very high costs for families and the society, as these patients need support and often institutionalization in the advanced stage [1]
High doses of the AChE-I donepezil were licensed in the United States (USA) for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage
Memantine and donepezil lead to improvements in moderateto-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity

Summary

Introduction

Alzheimer’s disease (AD), the most common adult-onset dementia, is associated with very high costs for families and the society, as these patients need support and often institutionalization in the advanced stage [1] Treatment, even if it cannot delay the disease progression, has a symptomatic effect on some cognitive, psychological, and behavioral symptoms. Elevated glutamate levels are associated with the development of neurotoxicity phenomena and this could explain the beneficial effect of memantine in the blocking of the negative consequences of elevated glutamate levels After initial skepticism, both the National Institute for Clinical Excellence (NICE) and the IQWIG (the German Institute for Quality and Efficiency in Healthcare) revised their original conclusions and recommended memantine in AD, primarily of the moderate-to-severe stage [4, 5]. This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24–52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials

Objectives

Methods

Results

Conclusion