Metabolomic biomarkers for (R, S)-ketamine and (S)-ketamine in treatment-resistant depression and healthy controls: A systematic review

IF 5 2区医学 Q1 CLINICAL NEUROLOGY

Bipolar Disorders Pub Date : 2024-02-07 DOI:10.1111/bdi.13412

Rakesh Kumar, Nicolas A. Nuñez, Neha Joshi, Boney Joseph, Alessandra Verde, Ashok Seshadri, Alfredo B. Cuellar Barboza, Larry J. Prokop, Gustavo C. Medeiros, Balwinder Singh

{"title":"Metabolomic biomarkers for (R, S)-ketamine and (S)-ketamine in treatment-resistant depression and healthy controls: A systematic review","authors":"Rakesh Kumar, Nicolas A. Nuñez, Neha Joshi, Boney Joseph, Alessandra Verde, Ashok Seshadri, Alfredo B. Cuellar Barboza, Larry J. Prokop, Gustavo C. Medeiros, Balwinder Singh","doi":"10.1111/bdi.13412","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Ketamine is increasingly used for treatment-resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 1859 abstracts were screened of which 11 were included for full-text review. Of these, a total of five articles were included (<i>N</i> = 147), including three RCTs (<i>n</i> = 129) and two open-label trials (<i>n</i> = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment-resistant bipolar depression (<i>n</i> = 22), unipolar depression (<i>n</i> = 91), and HCs (<i>n</i> = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post-infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed.</p>\n </section>\n </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bipolar Disorders","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bdi.13412","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Ketamine is increasingly used for treatment-resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs).

Methods

A comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine.

Results

A total of 1859 abstracts were screened of which 11 were included for full-text review. Of these, a total of five articles were included (N = 147), including three RCTs (n = 129) and two open-label trials (n = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment-resistant bipolar depression (n = 22), unipolar depression (n = 91), and HCs (n = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post-infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients.

Conclusions

This systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed.

查看原文本刊更多论文

难治性抑郁症和健康对照组中(R, S)-氯胺酮和(S)-氯胺酮的代谢生物标志物：系统综述。

背景：氯胺酮越来越多地被用于治疗难治性抑郁症（TRD），但其作用机制仍在研究之中。在这篇系统性综述中，我们评估了外消旋氯胺酮和埃斯氯胺酮在TRD患者和健康对照组（HCs）中的代谢组学生物标志物的现有证据：我们对多个数据库（Ovid MEDLINE®、Embase和Epub Ahead of Print）进行了全面检索，检索时间从每个数据库建立之初至2022年6月29日，检索语言不限。我们纳入了在 TRD 或 HC 中调查外消旋氯胺酮或艾司氯胺酮代谢组生物标志物的研究。我们的主要结果是研究接受氯胺酮/伊斯氯胺酮治疗的患者代谢物的变化，并探讨与氯胺酮/伊斯氯胺酮反应的关联：共筛选出1859篇摘要，其中11篇被纳入全文综述。其中，共纳入了 5 篇文章（N = 147），包括 3 项 RCT（n = 129）和 2 项开放标签试验（n = 18）。所有研究均使用外消旋氯胺酮，其中一项研究额外使用了艾司氯胺酮。纳入的研究评估了耐药性双相抑郁症患者（22 人）、单相抑郁症患者（91 人）和 HCs 患者（34 人）。纳入的研究报告称，氯胺酮可改变 TRD 患者的多种代谢物，包括酰基肉碱、脂类、犬尿氨酸（KYN）和精氨酸。研究表明，能量代谢、犬尿氨酸和精氨酸途径均有参与。在HCs中，乙酰肉碱在输注后下降，而在TRD患者中，氯胺酮输注后观察到的结果不一致：本系统综述提供的初步证据表明，氯胺酮可能会导致能量代谢和炎症过程中的几种重要通路发生变化。需要进行更大规模、更严格的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Bipolar Disorders 医学-精神病学

CiteScore

8.20

自引率

7.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Bipolar Disorders is an international journal that publishes all research of relevance for the basic mechanisms, clinical aspects, or treatment of bipolar disorders and related illnesses. It intends to provide a single international outlet for new research in this area and covers research in the following areas: biochemistry physiology neuropsychopharmacology neuroanatomy neuropathology genetics brain imaging epidemiology phenomenology clinical aspects and therapeutics of bipolar disorders Bipolar Disorders also contains papers that form the development of new therapeutic strategies for these disorders as well as papers on the topics of schizoaffective disorders, and depressive disorders as these can be cyclic disorders with areas of overlap with bipolar disorders. The journal will consider for publication submissions within the domain of: Perspectives, Research Articles, Correspondence, Clinical Corner, and Reflections. Within these there are a number of types of articles: invited editorials, debates, review articles, original articles, commentaries, letters to the editors, clinical conundrums, clinical curiosities, clinical care, and musings.