PDF(Pubmed)
Abstract：
Objective: Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. Method : The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Results: Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. Conclusion: The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.
摘要：
目的：抑郁症的现有治疗方法疗效有限，缓解率不理想。本研究旨在回顾研究谷氨酸受体调节剂在治疗难治性抑郁症患者中的作用的随机对照试验（RCTs）。方法：研究方案在PROSPERO（CRD42021225516）中注册。Scopus,ISIWebofScience,Embase,科克伦图书馆,谷歌学者，截至2020年9月,我们搜索了3个试验登记处,以寻找评估谷氨酸受体调节剂对难治性抑郁症的RCT.干预组和对照组在抑郁评分从基线到终点变化方面的差异被认为是主要结果。用于随机试验的Cochrane偏倚风险工具的第2版用于评估随机对照试验的质量。没有收到资金。结果：纳入38个RCT。根据纳入的研究，发现了氯胺酮的令人信服的证据（有或没有电惊厥治疗，静脉注射或其他形式)，一氧化二氮,金刚烷胺,和rislenemdaz(MK-0657)；MK-0657、金刚烷胺的结果，和一氧化二氮仅基于一项研究。锂，lanicemine,D-环丝氨酸,脱胶剂的疗效好坏参半，and,利鲁唑,和7-氯代尿酸与安慰剂大部分相当。针对氯胺酮以外的药物的研究数量有限。结论：由于RCT之间的高度异质性，该研究无法确定药物与安慰剂之间的统计学和临床意义之间的差异。然而，氯胺酮可作为TRD的有效药物；需要额外的研究来确定最佳剂量，疗效持续时间，和间隔。还建议进一步研究除氯胺酮以外的谷氨酸能系统调节剂对治疗抗性抑郁症的有效性。
