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Intraoperative Esketamine and Postpartum Depression Among Women With Cesarean Delivery: A Randomized Clinical Trial

Li Ren, Ting Zhang, B Zou, Xiaomei Su, Yuan Tao, Jixing Yang, Fangfang Lv, Peining Li, Fei Peng, Guodong Wu

Obstetric Anesthesia Digest November 18, 2025 DOI: 10.1097/01.aoa.0001171036.71757.fb (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized clinical trial Peer reviewed
Population New mothers who had cesarean birth
Intervention Esketamine
Topics Depression Esketamine Ketamine
Keywords Postpartum depression Randomized controlled trial Incidence geometry Depression economics Clinical trial Postpartum period Obstetrics Pregnancy Pediatrics Cesarean delivery
Citations 1
Key findings Esketamine may reduce the risk of postpartum depression following cesarean birth, but prior randomized clinical trials have shown mixed results.

Abstract

( JAMA Network Open . 2025;8(2):e2459331. doi: 10.1001/jamanetworkopen.2024.59331) Postpartum depression (PPD) is a widespread condition affecting about 17.7% of new mothers globally, with an even higher incidence of 21.4% reported in China. Cesarean birth (CB) appears to increase the risk of developing PPD compared to vaginal births. Given the growing recognition of esketamine, a derivative of ketamine, as a rapid-acting antidepressant, its potential use in PPD prevention has become a subject of interest. While prior randomized clinical trials (RCTs) have shown mixed results, there has been limited real-world evidence of its efficacy in typical clinical settings. The objective of this study was to examine the practical impact of esketamine in reducing the risk of PPD following CB.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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