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Memantine treatment for Japanese patients with moderate to severe Alzheimer’s disease: a meta-analysis of double-blind, randomized, placebo-controlled trials

Authors Kishi T, Matsunaga S, Iwata N

Received 12 September 2018

Accepted for publication 8 October 2018

Published 30 October 2018 Volume 2018:14 Pages 2915—2922


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Roger Pinder

Taro Kishi,1,* Shinji Matsunaga,1,2,* Nakao Iwata1

1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan; 2Department of Geriatrics and Cognitive Disorders, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan

*These authors contributed equally to this work

Purpose: Although previous meta-analyses of randomized trials in the world literature have provided strong evidence that supports the efficacy and safety of memantine for the treatment of patients with Alzheimer’s disease (AD), it is unclear whether the drug is beneficial in the treatment of Japanese patients with moderate to severe AD because of differences in the formulation and regimen of memantine and the cholinesterase inhibitor (ChEI) used in combination with memantine between the drugs made in Japan and those made in other countries. To address this issue, we conducted a meta-analysis on the efficacy and safety of memantine using data from only double-blind, randomized, placebo-controlled trials (DBRPCTs) in Japan on Japanese patients with moderate to severe AD.
Patients and methods: Our primary analysis was conducted using data from both memantine monotherapy (memantine vs placebo) and memantine combination therapy (memantine+ChEI vs ChEI+placebo) studies. The primary outcomes measured were cognitive function and behavioral disturbances. The secondary outcomes measured were the subscale scores of Behavioral Pathology in Alzheimer’s Disease (Behave-AD), discontinuation rate, and individual adverse events.
Results: Four DBRPCTs (n=1,328) were detected. Memantine was superior to the control in cognitive functions (standardized mean difference [SMD]=−0.31, 95% CI=−0.53, −0.10) and behavioral disturbances (SMD=−0.16, 95% CI=−0.28, −0.05). Only memantine monotherapy was superior in both outcomes. It was also superior to the control in delusions, aggression, and diurnal rhythm disturbances based on the Behave-AD subscale scores. Although memantine was associated with a lower incidence of AD progression than that of the control, the incidence of somnolence was higher with memantine. There were no significant differences in other safety outcomes, including all-cause discontinuation, between the groups.
Conclusion: Our results suggest that memantine is useful for the treatment of patients in Japan with moderate to severe AD even though our meta-analysis comprised only four DBRPCTs.

Keywords: Japanese patients, Alzheimer’s disease, memantine, cognitive functions, behavioral disturbances, meta-analysis

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