Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis

Taro Kishi, Shinji Matsunaga, Kazuto Oya, Ikuo Nomura, Toshikazu Ikuta, Nakao Iwata

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Background: The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n = 7,567; memantine versus placebo: N= 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N= 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95%CIs) = -0.34, -0.15, p < 0.00001, I2 = 35%] and BD (SMD = -0.16, 95%CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95%CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95%CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95%CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction inBDcompared with ChEIs without considerable heterogeneity(SMD = -0.11, 95%CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95%CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.

Original languageEnglish
Pages (from-to)401-425
Number of pages25
JournalJournal of Alzheimer's Disease
Volume60
Issue number2
DOIs
Publication statusPublished - 01-01-2017

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Memantine
Meta-Analysis
Alzheimer Disease
Confidence Intervals
Cholinesterase Inhibitors
Cognition
Placebos
Safety

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Kishi, Taro ; Matsunaga, Shinji ; Oya, Kazuto ; Nomura, Ikuo ; Ikuta, Toshikazu ; Iwata, Nakao. / Memantine for Alzheimer's Disease : An Updated Systematic Review and Meta-analysis. In: Journal of Alzheimer's Disease. 2017 ; Vol. 60, No. 2. pp. 401-425.
@article{ca31b0f0e2f244a791437d3441ae96a1,
title = "Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis",
abstract = "Background: The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n = 7,567; memantine versus placebo: N= 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N= 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95{\%} confidence intervals (95{\%}CIs) = -0.34, -0.15, p < 0.00001, I2 = 35{\%}] and BD (SMD = -0.16, 95{\%}CIs = -0.29, -0.04, p = 0.01, I2 = 52{\%}) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95{\%}CIs = -0.34, -0.07, p = 0.003, I2 = 36{\%}). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95{\%}CIs = -0.36, -0.03, p = 0.02, I2 = 77{\%}) and a trend of CF improvement (SMD = -0.11, 95{\%}CIs = -0.22, 0.01, p = 0.06, I2 = 56{\%}). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction inBDcompared with ChEIs without considerable heterogeneity(SMD = -0.11, 95{\%}CIs = -0.21, -0.01, p = 0.04, I2 = 40{\%}). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95{\%}CIs = -0.31, -0.05, p = 0.006, I2 = 49{\%}). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.",
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Memantine for Alzheimer's Disease : An Updated Systematic Review and Meta-analysis. / Kishi, Taro; Matsunaga, Shinji; Oya, Kazuto; Nomura, Ikuo; Ikuta, Toshikazu; Iwata, Nakao.

In: Journal of Alzheimer's Disease, Vol. 60, No. 2, 01.01.2017, p. 401-425.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Memantine for Alzheimer's Disease

T2 - An Updated Systematic Review and Meta-analysis

AU - Kishi, Taro

AU - Matsunaga, Shinji

AU - Oya, Kazuto

AU - Nomura, Ikuo

AU - Ikuta, Toshikazu

AU - Iwata, Nakao

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n = 7,567; memantine versus placebo: N= 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N= 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95%CIs) = -0.34, -0.15, p < 0.00001, I2 = 35%] and BD (SMD = -0.16, 95%CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95%CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95%CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95%CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction inBDcompared with ChEIs without considerable heterogeneity(SMD = -0.11, 95%CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95%CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.

AB - Background: The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n = 7,567; memantine versus placebo: N= 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N= 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95%CIs) = -0.34, -0.15, p < 0.00001, I2 = 35%] and BD (SMD = -0.16, 95%CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95%CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95%CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95%CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction inBDcompared with ChEIs without considerable heterogeneity(SMD = -0.11, 95%CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95%CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.

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DO - 10.3233/JAD-170424

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