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ABSTRACT
Introduction: Currently, five pharmacotherapeutic options are available to treat Alzheimer’s disease: memantine; the three cholinesterase inhibitors donepezil, galantamine, and rivastigmine; and combination treatments with memantine and one cholinesterase inhibitor. Selection of the best course of treatment is based upon the evidence gathered by systematic reviews and meta-analyses of randomized controlled trials.
Areas covered: This article provides a risk–benefit analysis of these treatments using evidence from meta-analyses on their safety and their efficacy.
Expert opinion: Memantine improves cognitive functions and behavioral disturbances more efficiently than the placebo, both as monotherapy and in combination with donepezil. Although memantine monotherapy and combination therapy are associated with a few individual adverse events such as somnolence, it is well-tolerated and its safety (all-cause discontinuation) is comparable or superior to that of the placebo (agitation). Pooled cholinesterase inhibitors are superior to the placebo in the improvement of cognitive functions, but not behavioral disturbances and they are not well-tolerated, as evaluated by the high discontinuation rate. Donepezil (10 mg/day) and oral rivastigmine and galantamine monotherapies carry the risk for some adverse events including gastrointestinal symptoms. Therefore, we consider that combined treatment with memantine and donepezil is the most useful treatment for Alzheimer’s disease.
Acknowledgments
A part of data which we could not get enough information from published articles nor unpublished studies was provided by Daiichi Sankyo Co., Ltd.
Declaration of interest
SM, TK, IN, KS, MO, TI, and NI declare that they have no direct conflicts of interest relevant to this study. No grant support or other sources of funding were used to conduct this study or prepare this manuscript. SM has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Meiji, MSD, Novartis, Otsuka, and Tanabe-Mitsubishi and has received a Fujita Health University School of Medicine research grant and a grant-in-aid for Young Scientists (B). TK has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Yoshitomi, and Tanabe-Mitsubishi and has received a Health Labour Sciences Research Grant and a Fujita Health University School of Medicine research grant. IN has received speaker’s honoraria from Meiji, MSD and Otsuka. IS has received speaker’s honoraria from Otsuka. MO has received speaker’s honoraria from Meiji. TI has received speaker’s honoraria from Eli Lilly, Daiichi Sankyo, and Dainippon Sumitomo and has been a consultant for Dainippon Sumitomo.NI has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and has had research grants from GlaxoSmithKline, Meiji, and Otsuka.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contributions
Study concept and design were performed by SM and TK. The manuscript was written by all authors. NI supervised the review.