Effect of Perioperative Ketamine on Early Postpartum Depressive Symptoms Following Cesarean Section: A Meta-Analysis.
Samantha Siu, Peter Hsin, Sarah Simon, Talia Lall, Anabel Lin, Da Young Lee, Rose Berkun, Patricia Junquera
Cureus April 1, 2026 DOI: 10.7759/cureus.107180 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Population | Adults undergoing elective cesarean section |
| Interventions | ketamine esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Cesarean section Meta-analysis Peri-operative medicine Postpartum depression |
| Key findings | Perioperative ketamine or esketamine was associated with a significant reduction in early postpartum depressive symptoms compared with control (SMD = -0.36; 95% CI -0.49 to -0.22). |
Abstract
Postpartum depression (PPD) is a common condition associated with adverse maternal and infant outcomes. Higher rates have been observed following cesarean delivery, prompting interest in perioperative preventive strategies. Ketamine has demonstrated rapid antidepressant effects and may provide psychiatric benefits beyond analgesia. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating perioperative ketamine or esketamine for early postpartum depressive symptom reduction in adults undergoing elective cesarean section. PubMed, ScienceDirect, and PsycINFO were searched for studies published between January 2015 and September 2025. Eligible studies reported Edinburgh Postnatal Depression Scale (EPDS) scores between postoperative days 3 and 14. A random-effects model was used to pool standardized mean differences (SMDs), with heterogeneity assessed using the I² statistic. Six randomized controlled trials met the inclusion criteria. Perioperative ketamine or esketamine was associated with a significant reduction in early postpartum depressive symptoms compared with control (SMD = -0.36; 95% CI -0.49 to -0.22). Moderate heterogeneity was observed (I² = 47.5%), with a consistent direction of effect favoring ketamine. These findings suggest that perioperative ketamine may reduce early postpartum depressive symptom burden, though further studies are needed to clarify optimal dosing, timing, and long-term clinical impact.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cites 7
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology March 1, 2025
- Beyond NMDA Receptors: A Narrative Review of Ketamine's Rapid and Multifaceted Mechanisms in Depression Treatment. International Journal of Molecular Sciences December 20, 2024
- The effect of a subclinical dose of esketamine on depression and pain after cesarean section: A prospective, randomized, double-blinded controlled trial. Medicine November 1, 2024
- Ketamine in neuropsychiatric disorders: an update. Neuropsychopharmacology January 2024
and 2 more in the library