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

Abstract

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

Acknowledgments

Part of the data which we could not obtain from published articles or unpublished studies was provided by Daiichi Sankyo Co., Ltd.

Disclosure

Drs Kishi, Matsunaga, and Iwata 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. Dr Kishi 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 for other studies. Dr Matsunaga 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) for other studies. Dr Iwata has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and has received research grants from GlaxoSmithKline, Meiji, and Otsuka for other studies.