A meta-analysis update evaluating the treatment effects of donepezil alone versus donepezil combined with memantine for Alzheimer's disease

IF 2.9 Q3 NEUROSCIENCES

IBRO Neuroscience Reports Pub Date : 2025-05-29 DOI:10.1016/j.ibneur.2025.05.016

Sajjad Hajihosseini , Seyed Amirali Zakavi , Zahra Farrokhi , Mahnaz Amanzadeh , Parham Panahi , Mina Mahram , Nima Eftekhari , Masoud Noroozi , Mohammad Javad Ebrahimi , Alaleh Alizadeh , Pegah Refahi , Melika Arab Bafrani , Maral Moafi , Niloofar Deravi

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Abstract

Background

Alzheimer's disease (AD) remains a significant global health problem, with ongoing debates about the most effective treatment approach. While donepezil monotherapy has been traditionally used, recent interest has focused on combining it with memantine. This updated meta-analysis aimed to compare the efficacy of donepezil monotherapy versus its combination with memantine for treating AD.

Method

A literature search was conducted in the PubMed, Scopus, and Google Scholar databases up to February 14, 2024. Randomized controlled trials (RCTs) comparing donepezil monotherapy with donepezil combined with memantine in AD patients were included. The quality of each selected study was assessed using the Joanna Briggs Institute (JBI) risk-of-bias tool. Data on cognitive function, measured using the Mini-Mental State Examination (MMSE) and the Severe Impairment Battery (SIB), were extracted and analyzed using a random-effects model.

Results

A total of four RCTs, including 1930 patients, met the inclusion criteria. Analysis using a forest plot revealed no significant difference in MMSE scores between monotherapy and combination therapy (OR = 0.54, 95 % CI: 0.06–4.60, p > 0.05). However, SIB scores showed a significant improvement with combination therapy (OR = 7.00, 95 % CI: 1.13–43.24, p < 0.05). Both analyses exhibited high heterogeneity (I² = 72 % for MMSE; I² = 89 % for SIB). The funnel plots suggested minor publication bias for the MMSE outcomes, but some asymmetry was observed in the results for SIB.

Conclusion

This meta-analysis suggests that combination therapy with donepezil and memantine significantly benefits patients with severe cognitive impairment, as assessed by the SIB, compared to donepezil monotherapy. However, no significant advantage was observed in MMSE scores. The high heterogeneity among studies highlights the need for cautious interpretation and calls for larger, well-designed randomized controlled trials to further elucidate the comparative efficacy of these two therapeutic approaches in Alzheimer's disease.

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一项评估多奈哌齐单用与多奈哌齐联合美金刚治疗阿尔茨海默病疗效的最新荟萃分析

阿尔茨海默病（AD）仍然是一个重大的全球健康问题，关于最有效的治疗方法的争论正在进行中。虽然传统上使用多奈哌齐单药治疗，但最近的兴趣集中在将其与美金刚联合使用。这项最新的荟萃分析旨在比较多奈哌齐单药治疗与美刚联合治疗AD的疗效。方法对截至2024年2月14日的PubMed、Scopus和b谷歌Scholar数据库进行文献检索。纳入比较多奈哌齐单药治疗与多奈哌齐联合美金刚治疗AD患者的随机对照试验（RCTs）。采用乔安娜布里格斯研究所（JBI）的偏倚风险工具对每项选定研究的质量进行评估。使用简易精神状态检查（MMSE）和严重损伤电池（SIB）测量认知功能数据，并使用随机效应模型进行提取和分析。结果符合纳入标准的患者共4项rct，共1930例。森林图分析显示，单药治疗和联合治疗的MMSE评分无显著差异（OR = 0.54, 95 % CI: 0.06-4.60, p >； 0.05）。然而，联合治疗后SIB评分有显著改善（OR = 7.00, 95 % CI: 1.13-43.24, p <； 0.05）。两项分析均显示出高度异质性(I²= 72 %的MMSE；I²= 89 % （SIB）。漏斗图显示MMSE结果有轻微的发表偏倚，但SIB结果有一些不对称。结论：该荟萃分析表明，与多奈哌齐单药治疗相比，多奈哌齐和美金刚联合治疗对严重认知障碍患者有显著益处。然而，在MMSE评分中没有观察到明显的优势。研究之间的高度异质性强调了谨慎解释的必要性，并呼吁进行更大规模、设计良好的随机对照试验，以进一步阐明这两种治疗方法在阿尔茨海默病中的比较疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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