PubMed日本語 - アルツハイマー病患者におけるメマンチンは、ドネペジルを受ける:有効性の新しい分析と併用療法のための安全性。―QLifePro医療翻訳医療翻訳 QLifePro


Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy.


Published date



Alireza Atri, José L Molinuevo, Ole Lemming, Yvonne Wirth, Irena Pulte, David Wilkinson


Memory Assessment & Research Centre, Tom Rudd Unit, Moorgreen Hospital, Botley Road, West End, Southampton, SO30 3JB, UK.


INTRODUCTION: Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD.


METHODS: Post hoc meta-analyses of data combined from two 24-week, randomised, double-blind, placebo-controlled trials of memantine 20 mg/day versus placebo, added to a stable cholinesterase inhibitor, were conducted. Data were included for all patients receiving donepezil 10 mg/day with Mini-Mental State Examination (MMSE) scores < 20 (n = 510). Efficacy was assessed using measures of cognition, function, and global status. Furthermore, marked clinical worsening, defined as concurrent deterioration from baseline in the three main efficacy domains, and safety, measured by treatment-emergent adverse events, were assessed. Analyses were performed for patients with moderate to severe AD (MMSE 5-19; MOD-SEV subgroup), and also for patients with moderate AD (MMSE 10-19; MOD subgroup; n = 367).


RESULTS: At week 24, in the MOD-SEV subgroup, patients receiving memantine added to donepezil significantly outperformed those receiving placebo added to donepezil in measures of cognition (P < 0.0001), function (P = 0.02), and global status (P = 0.010), with standardised mean differences (SMDs) of 0.36, 0.21, and 0.23, respectively (all last observation carried forward). Similarly, in the MOD subgroup, significant benefits were observed for cognition (P = 0.008), function (P = 0.04) and global status (P = 0.008), with SMDs of 0.28, 0.21, and 0.28, respectively. Significantly fewer patients receiving memantine added to donepezil showed marked clinical worsening than those receiving placebo added to donepezil, in both subgroups (MOD-SEV: 8.7% versus 20.4%, P = 0.0002; MOD: 5.9% versus 15.0%, P = 0.006). The incidence of adverse events was similar between treatment groups.


CONCLUSIONS: These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful.



データは、ミニ-精神状態検査(MMSE)スコア<20(n = 510)で、ドネペジル10mg/日の投与を受けたすべての患者のために含まれた。
分析は、中等度から重度のAD(MMSE 5-19; MOD-SEVサブグループ)を有する患者のために、更に、穏健なAD(MMSE 10-19; MODサブグループ; n = 367)を有する患者のために行われた。

結果週24に、MOD-SEVサブグループにおいて、それぞれ0.36、0.21および0.23(進められるすべての最後の観察)の標準化された平均差(SMDs)で、有意にドネペジルに加えられるメマンチンの投与を受けた患者は、認識(P < 0.0001)、機能(P = 0.02)と全体的な状態(P = 0.010)の計測でドネペジルに加えられるプラセボ群を上回った。
同様に、MODサブグループにおいて、それぞれ0.28、0.21および0.28のSMDsで、有意の有益性は、認識(P = 0.008)、機能(P = 0.04)と全体的な状態(P = 0.008)のために観察された。
プラセボ群が、両方のサブグループ(MOD-SEV:8.7%対20.4%(P = 0.0002); MOD:5.9%対15.0%(P = 0.006))で、ドネペジルを増したより有意に少しのドネペジルに加えられるメマンチンの投与を受けた患者は、臨床に悪化することと記録されて現れた。


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