Hajihosseini Sajjad, Zakavi Seyed Amirali, Farrokhi Zahra, Amanzadeh Mahnaz, Panahi Parham, Mahram Mina, Eftekhari Nima, Noroozi Masoud, Ebrahimi Mohammad Javad, Alizadeh Alaleh, Refahi Pegah, Bafrani Melika Arab, Moafi Maral, Deravi Niloofar
Student Research Committee, Tehran University of Medical Sciences, Tehran, Iran.
Students Research Committee, school of medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
IBRO Neurosci Rep. 2025 May 29;19:72-82. doi: 10.1016/j.ibneur.2025.05.016. eCollection 2025 Dec.
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.
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.
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.
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.
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一直存在争议。虽然传统上使用多奈哌齐单药治疗，但最近的研究兴趣集中在将其与美金刚联合使用。这项更新的荟萃分析旨在比较多奈哌齐单药治疗与多奈哌齐联合美金刚治疗AD的疗效。
截至2024年2月14日，在PubMed、Scopus和谷歌学术数据库中进行了文献检索。纳入了比较AD患者多奈哌齐单药治疗与多奈哌齐联合美金刚治疗的随机对照试验（RCT）。使用乔安娜·布里格斯研究所（JBI）偏倚风险工具评估每项入选研究的质量。使用简易精神状态检查表（MMSE）和严重损害量表（SIB）测量的认知功能数据被提取，并使用随机效应模型进行分析。
共有四项RCT，包括1930名患者，符合纳入标准。使用森林图分析显示，单药治疗和联合治疗之间的MMSE评分没有显著差异（OR = 0.54，95%CI：0.06 - 4.60，p > 0.05）。然而，联合治疗的SIB评分显示出显著改善（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（MMSE的I² = 72%；SIB的I² = 89%）。漏斗图表明MMSE结果存在轻微的发表偏倚，但在SIB结果中观察到一些不对称性。
这项荟萃分析表明，与多奈哌齐单药治疗相比，多奈哌齐与美金刚联合治疗对严重认知障碍患者（通过SIB评估）有显著益处。然而，在MMSE评分方面未观察到显著优势。研究之间的高度异质性凸显了谨慎解读的必要性，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。
