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  • Systematic Review
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Efficacy and safety of esketamine on major depression, postpartum depression and perioperative depression: a systematic review and meta-analysis

Molecular Psychiatry (2025)Cite this article

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Abstract

This review and meta-analysis aimed to evaluate esketamine in managing major depressive disorder (MDD) / treatment resistant depression (TRD), preventing postpartum depression (PPD) and postoperative depression, including comparisons within and between administrations. Five databases (Pubmed, MEDLINE, Embase, Web of science and the Cochrane Library) were searched up to July 24, 2025. Randomized clinical trials investigating esketamine for depression, compared with control group were included. Efficacy outcomes included depression scales, remission rate, response rate and depression incidence rates. Safety outcomes included adverse events reported in more than two comparisons. Standardized mean differences (SMDs) and Relative risks (RRs) with their corresponding 95% confidential intervals (CIs) were estimated using fixed- or random-effects models. Administration regimes were ranked using surface under the cumulative ranking. Of 12,285 studies identified, 67 trials with 11,553 participants were included: 19 trials on MDD/TRD, 18 studies on PPD and 30 studies on postoperative depression. The overall pooled SMDs, compared with comparator, showed effective in treating and preventing depression (MDD -0.36, 95%CI -0.49, -0.24; PPD for postpartum 6 week -0.40, 95%CI -0.78, -0.02, and postoperative depression for postoperative 3 month -0.82, 95%CI -1.46, -0.18). Intravenous administration yields the greatest effect in treating MDD/TRD and preventing PPD, no matter of the measured outcome (scales scores, response rate of MDD/TRD or incidence rate of PPD or postoperative depression). Esketamine was associated with higher incidences of dizziness in both therapeutic and preventive effects. These findings highlight both short- and long-term efficacy of eskatemine in treating MDD/TRD, and preventing PPD and postoperative depression, with efficacy differing across administration routes.

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Fig. 1: Forest plot of efficacy in treating MDD/TRD.
Fig. 2: Surface under the cumulative ranking curve (SUCRA) analysis for administration regimes in MDD/TRD.
Fig. 3: Forest plot of efficacy in reducing depression scores for preventing postpartum and postoperative depression.

Data availability

Data in this systematic review and meta-analysis were extracted from published studies available on the internet.

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Acknowledgements

CXH is supported by Education Department of Anhui (2024AH030026), Anhui provincial institute of translational medicine (2022zhyx-C53). LL is supported by Joint Innovation Team for Clinical & Basic Research (202404), the National Programs for Brain Science and Brain-like Intelligence Technology of China (STI2030-Major Projects, 2021ZD0200800, 2021ZD0200700), National Key Research and Development Program of China (2021YFC0863700), and the National Natural Science Foundation of China (82288101). This work was funded in part by AR with the Hessian Ministry of Science and Arts (HMWK) LOEWE program (LOEWE Centre DYNAMIC), and LHH with Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan (2024B0034).

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Author notes

  1. These authors contributed equally: Chunxia Huang, Linhui Hu.

Authors and Affiliations

  1. Institute of Brain Science and Brain-inspired Research, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China

    Chunxia Huang

  2. Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital of Anhui Medical University, Key Laboratory of Anesthesiology and Perioperative Medicine of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China

    Chunxia Huang, Wu Liu, Ye Zhang & Qi Xue

  3. Department of Hematology, the Second Affiliated Hospital of Nanchang University, Nanchang, China

    Linhui Hu

  4. Jiangxi Provincial Key Laboratory of Hematological Diseases, Nanchang, China

    Linhui Hu

  5. Department of Psychology and Sleep Medicine, the Second affiliated Hospital of Anhui Medical University, Hefei, China

    Feng Geng

  6. Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, SARHong Kong, China

    Gordon Tin Chun Wong

  7. Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany

    Andreas Reif

  8. National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, School of Public Health, Peking University, Beijing, China

    Yanping Bao

  9. Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China

    Lin Lu

  10. Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

    Lin Lu

Authors
  1. Chunxia Huang
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  2. Linhui Hu
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  3. Wu Liu
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  4. Feng Geng
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  6. Ye Zhang
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  8. Yanping Bao
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  9. Qi Xue
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  10. Lin Lu
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Contributions

CXH: conceptualisation, data curation, formal analysis, writing-original draft, writing-review and editing, funding and supervision. LHH: conceptualisation, data curation, formal analysis, writing-original draft, writing-review and editing, and funding. WL: investigation, writing-original draft. FG: investigation, writing-review and editing. GTCW: writing-original draft and writing-review and editing. YZ: writing-review and editing. AR: writing-review and editing and funding. YPB: writing-original draft, writing-review and editing, and supervision. QX: conceptualisation, data curation, formal analysis, writing-original draft, writing-review and editing, and supervision. LL: conceptualisation, writing-review and editing, funding and supervision.

Corresponding authors

Correspondence to Chunxia Huang, Qi Xue or Lin Lu.

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Huang, C., Hu, L., Liu, W. et al. Efficacy and safety of esketamine on major depression, postpartum depression and perioperative depression: a systematic review and meta-analysis. Mol Psychiatry (2025). https://doi.org/10.1038/s41380-025-03320-6

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