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

Taro Kishi, Shinji Matsunaga, Nakao Iwata

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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.

Original languageEnglish
Pages (from-to)2915-2922
Number of pages8
JournalNeuropsychiatric Disease and Treatment
Volume14
DOIs
Publication statusPublished - 01-01-2018

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Memantine
Meta-Analysis
Alzheimer Disease
Randomized Controlled Trials
Placebos
Therapeutics
Cholinesterase Inhibitors
Japan
Safety
Cognition
Delusions
Incidence
Circadian Rhythm
Aggression
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

@article{d7d569b486bb4c68884d700a1ea7bcb7,
title = "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.",
author = "Taro Kishi and Shinji Matsunaga and Nakao Iwata",
year = "2018",
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day = "1",
doi = "10.2147/NDT.S187320",
language = "English",
volume = "14",
pages = "2915--2922",
journal = "Neuropsychiatric Disease and Treatment",
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T1 - Memantine treatment for Japanese patients with moderate to severe Alzheimer’s disease

T2 - A meta-analysis of double-blind, randomized, placebo-controlled trials

AU - Kishi, Taro

AU - Matsunaga, Shinji

AU - Iwata, Nakao

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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