Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.

IF 2.7 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Clinical Drug Investigation Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI:10.1007/s40261-025-01465-4
Houlin Hong, Jack Donlon, Martin Schaefer, Susanne Sarkar, Dragana Bugarski-Kirola, Mujeeb U Shad, Wei Hou, Matthias Kirschner, Sajoy P Varghese, Ludmil Mitrev, Valentina Echeverria, John Dibato, Selene R T Veerman, Rohit Aiyer, Thomas N Ferraro, Gerardo Villarreal, Shafiqur Rahman, Trevor W Stone, Maju M Koola
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引用次数: 0

Abstract

Background: Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist with favorable safety and side effect profiles. There is a growing body of evidence for memantine as an adjunctive therapy for the positive, negative, and cognitive symptoms of schizophrenia.

Objective: This meta-analysis examined the efficacy of memantine as an add-on to treatment with antipsychotic(s) for the primary negative symptoms (PNS) of schizophrenia.

Methods: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched for relevant publications in PubMed, Cochrane Library, PsycINFO, Embase, and China Journal Net databases from inception using the following search terms: memantine, schizophrenia, randomized controlled trials (RCTs), RCT, and clinical trial. Searches were limited to English- and Chinese-language articles to date. Standardized mean differences (SMDs) with 95% confidence intervals were calculated using RevMan 5.4 to assess the effect size. Risk of bias was assessed using RoB 2.0.

Results: In total, 13 RCTs were identified (N = 681). Memantine was superior to placebo in treating negative symptoms, with an SMD of 0.79 (p = 0.0001, N = 631, 12 RCTs). Analysis of three studies whose corresponding authors provided original datasets showed an SMD of 2.16 (p = 0.25, N = 97) after adjusting for change in psychosis, depression, and extrapyramidal symptoms, suggesting that memantine is efficacious in treating PNS. Additionally, cognitive testing significantly improved, with an SMD of 0.66 (p = 0.0001, N = 395, eight RCTs). Positive symptoms were not significantly improved (SMD = 0.24, p = 0.1, N = 631, 12 RCTs).

Conclusions: To our knowledge, this is the first study showing a large effect size for treating PNS with memantine. Although statistical significance was not reached because of the small sample size (N = 97), the results were as expected because drugs such as memantine that act at NMDA receptors are unlikely to be effective as stand-alone treatments. Future RCTs should evaluate NMDAergic drugs in combination with complementary medications to optimize therapeutic effects for all three domains of schizophrenia psychopathology.

美金刚治疗精神分裂症原发性阴性症状:一项随机对照试验的荟萃分析
背景:美金刚是一种n -甲基- d -天冬氨酸(NMDA)受体拮抗剂,具有良好的安全性和副作用。有越来越多的证据表明美金刚可以作为精神分裂症阳性、阴性和认知症状的辅助治疗。目的:本荟萃分析检验了美金刚作为抗精神病药物治疗精神分裂症原发性阴性症状(PNS)的附加疗法的疗效。方法:我们遵循系统评价和荟萃分析的首选报告项目(PRISMA)指南,从一开始就在PubMed、Cochrane图书馆、PsycINFO、Embase和中国期刊网数据库中检索相关出版物,使用以下搜索词:美金刚、精神分裂症、随机对照试验(RCTs)、随机对照试验(RCT)和临床试验。到目前为止,搜索仅限于英文和中文文章。采用RevMan 5.4计算具有95%置信区间的标准化平均差异(SMDs)来评估效应大小。偏倚风险采用rob2.0进行评估。结果:共纳入13项rct (N = 681)。美金刚在治疗阴性症状方面优于安慰剂,SMD为0.79 (p = 0.0001, N = 631, 12项随机对照试验)。对三篇由相应作者提供原始数据集的研究的分析显示,在调整精神病、抑郁和锥体外系症状的变化后,SMD为2.16 (p = 0.25, N = 97),提示美金刚对PNS有效。此外,认知测试显著改善,SMD为0.66 (p = 0.0001, N = 395, 8项随机对照试验)。阳性症状无明显改善(SMD = 0.24, p = 0.1, N = 631, 12个rct)。结论:据我们所知,这是第一个显示用美金刚治疗PNS有很大效果的研究。虽然由于样本量小(N = 97),没有达到统计学意义,但结果如预期的那样,因为作用于NMDA受体的药物,如美金刚,不太可能作为单独治疗有效。未来的随机对照试验应该评估NMDAergic药物与补充药物的结合,以优化精神分裂症精神病理的所有三个领域的治疗效果。
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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来源期刊
CiteScore
5.90
自引率
3.10%
发文量
108
审稿时长
6-12 weeks
期刊介绍: Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.
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