Intravenous ketamine versus esketamine for depression: a systematic review and meta-analysis.

IF 5 3区医学 Q2 PHARMACOLOGY & PHARMACY

Therapeutic Advances in Psychopharmacology Pub Date : 2025-11-13 eCollection Date: 2025-01-01 DOI:10.1177/20451253251394127

Ahmed Elmosalamy, Idil Tarikogullari, Liliana Patarroyo-Rodriguez, Gwen Wilson, Jennifer L Vande Voort, Simon Kung, Mark A Frye, Balwinder Singh

{"title":"Intravenous ketamine versus esketamine for depression: a systematic review and meta-analysis.","authors":"Ahmed Elmosalamy, Idil Tarikogullari, Liliana Patarroyo-Rodriguez, Gwen Wilson, Jennifer L Vande Voort, Simon Kung, Mark A Frye, Balwinder Singh","doi":"10.1177/20451253251394127","DOIUrl":null,"url":null,"abstract":"Background: Depression affects approximately 5.7% of adults worldwide, and around one-third of these individuals develop treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (administered IV or intranasally (IN)) are novel treatment options for TRD; however, only IN esketamine currently holds FDA approval.Objectives: Compare the acute effectiveness of IV ketamine with esketamine (IV or IN) in adults with TRD.Design: Mantel-Haenszel random-effects meta-analysis of head-to-head studies. Response and remission at study end point were co-primary outcomes, expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses explored the impact of diagnosis, study type, and publication format; heterogeneity was quantified with I 2.Data sources and methods: MEDLINE, Embase, Cochrane, APA Psycinfo, and Scopus were searched from inception through 19 March 2025. Eligible studies enrolled adults with unipolar or bipolar depression directly comparing IV ketamine with esketamine and reporting response or remission.Results: Screening 1089 records identified eight studies (n = 978). Seven observational studies (n = 915) comparing IV ketamine with IN esketamine were included in the meta-analysis, while one randomized controlled trial (RCT) comparing IV formulations was summarized qualitatively. Pooled response from six studies gave OR = 1.26 (95% CI, 0.92-1.71; p = 0.15) and remission from seven studies gave OR = 1.31 (95% CI, 0.93-1.86; p = 0.12), both nonsignificantly favoring IV ketamine with negligible heterogeneity (I 2 = 0%). Sensitivity analyses excluding bipolar depression or abstract-only reports yielded similar effect estimates, reinforcing the robustness of the findings. Evidence across three studies for faster onset with IV ketamine ranged from significant in one study to modest trends in two.Conclusion: Based on the currently available comparative evidence, which is almost entirely observational, IV ketamine and IN esketamine show comparable acute response and remission rates, though IV ketamine may act faster. Large head-to-head RCTs are needed to confirm these findings.Trial registration: The study protocol was prospectively registered on the Open Science Framework (OSF) at https://osf.io/5jzev.","PeriodicalId":23127,"journal":{"name":"Therapeutic Advances in Psychopharmacology","volume":"15 ","pages":"20451253251394127"},"PeriodicalIF":5.0000,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12615959/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/20451253251394127","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Depression affects approximately 5.7% of adults worldwide, and around one-third of these individuals develop treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (administered IV or intranasally (IN)) are novel treatment options for TRD; however, only IN esketamine currently holds FDA approval.

Objectives: Compare the acute effectiveness of IV ketamine with esketamine (IV or IN) in adults with TRD.

Design: Mantel-Haenszel random-effects meta-analysis of head-to-head studies. Response and remission at study end point were co-primary outcomes, expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses explored the impact of diagnosis, study type, and publication format; heterogeneity was quantified with I ².

Data sources and methods: MEDLINE, Embase, Cochrane, APA Psycinfo, and Scopus were searched from inception through 19 March 2025. Eligible studies enrolled adults with unipolar or bipolar depression directly comparing IV ketamine with esketamine and reporting response or remission.

Results: Screening 1089 records identified eight studies (n = 978). Seven observational studies (n = 915) comparing IV ketamine with IN esketamine were included in the meta-analysis, while one randomized controlled trial (RCT) comparing IV formulations was summarized qualitatively. Pooled response from six studies gave OR = 1.26 (95% CI, 0.92-1.71; p = 0.15) and remission from seven studies gave OR = 1.31 (95% CI, 0.93-1.86; p = 0.12), both nonsignificantly favoring IV ketamine with negligible heterogeneity (I ² = 0%). Sensitivity analyses excluding bipolar depression or abstract-only reports yielded similar effect estimates, reinforcing the robustness of the findings. Evidence across three studies for faster onset with IV ketamine ranged from significant in one study to modest trends in two.

Conclusion: Based on the currently available comparative evidence, which is almost entirely observational, IV ketamine and IN esketamine show comparable acute response and remission rates, though IV ketamine may act faster. Large head-to-head RCTs are needed to confirm these findings.

Trial registration: The study protocol was prospectively registered on the Open Science Framework (OSF) at https://osf.io/5jzev.

Abstract Image

查看原文本刊更多论文

静脉注射氯胺酮与艾氯胺酮治疗抑郁症：系统回顾和荟萃分析。

背景：抑郁症影响全球约5.7%的成年人，其中约三分之一的人患有难治性抑郁症（TRD）。静脉注射氯胺酮和艾氯胺酮（静脉或鼻内给药）是治疗TRD的新选择；然而，目前只有艾氯胺酮获得了FDA的批准。目的：比较静脉注射氯胺酮和静脉注射氯胺酮治疗成人TRD的急性疗效。设计：对头对头研究进行Mantel-Haenszel随机效应meta分析。研究结束时的缓解和缓解是共同的主要结局，用95%置信区间（ci）的优势比（ORs）表示。亚组分析和敏感性分析探讨了诊断、研究类型和出版格式的影响；异质性用i2量化。数据来源和方法：MEDLINE， Embase, Cochrane, APA Psycinfo， Scopus检索自成立至2025年3月19日。符合条件的研究纳入了患有单极或双相抑郁症的成年人，直接比较静脉注射氯胺酮和艾氯胺酮，并报告反应或缓解。结果：筛选1089份记录，确定了8项研究（n = 978）。meta分析纳入了7项比较静脉氯胺酮与静脉氯胺酮的观察性研究（n = 915），并对1项比较静脉氯胺酮处方的随机对照试验（RCT）进行了定性总结。6项研究的综合反应OR = 1.26 (95% CI, 0.92-1.71; p = 0.15)， 7项研究的缓解OR = 1.31 (95% CI, 0.93-1.86; p = 0.12)，均无显著性倾向于IV氯胺酮，异质性可忽略不计（I 2 = 0%）。敏感性分析排除双相抑郁症或仅摘要报告得出类似的效果估计，加强了研究结果的稳健性。三项研究的证据表明，静脉注射氯胺酮起效更快，其中一项研究的证据显著，而另两项研究的证据则较为温和。结论：根据目前可获得的比较证据，这些证据几乎完全是观察性的，静脉注射氯胺酮和静脉注射氯胺酮具有相当的急性反应和缓解率，尽管静脉注射氯胺酮可能更快起作用。需要大规模的头对头随机对照试验来证实这些发现。试验注册：研究方案在开放科学框架（OSF）上注册，网址为https://osf.io/5jzev。

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

Therapeutic Advances in Psychopharmacology Multiple-

CiteScore

7.90

自引率

2.40%

发文量

审稿时长

10 weeks

期刊介绍： Therapeutic Advances in Psychopharmacology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of psychopharmacology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in psychopharmacology, providing a forum in print and online for publishing the highest quality articles in this area.