Peripartum Esketamine: A Narrative Review of Analgesia, Postpartum Depressive Symptoms, Sleep-Related Outcomes, and Safety.
Zhaoying Zhong, Baozhen Liao, Donglan Peng, Xiaohui Cao, Jianqiang Zeng
Drug Design, Development and Therapy October 17, 2026 DOI: 10.2147/dddt.s646618 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Randomized Peer reviewed |
|---|---|
| Intervention | Esketamine |
| Dose | low-dose |
| Measures | EPDS |
| Topics | Esketamine Ketamine |
| Keywords | Humans Pain Depression, postpartum Sleep Pregnancy Female Peripartum period Analgesia Cesarean delivery Postpartum depressive symptoms Peripartum care |
| Key findings | The authors conclude that esketamine may serve as an individualized adjunct in peripartum care but that current evidence does not support routine prophylactic use. Evidence is most consistent for short-term analgesic benefit; opioid-sparing effects are inconsistent. Several randomized trials suggest low-dose peri-delivery esketamine may reduce early EPDS-defined screen-positive postpartum depressive symptoms, though structured diagnostic evidence remains limited, and sleep-related evidence is preliminary and subjective. |
Abstract
Pain, depressive symptoms, and sleep disruption frequently overlap during the peripartum period, although their relationships are associative rather than established as causal. Esketamine, an N-methyl-D-aspartate receptor antagonist, has attracted interest as a peripartum intervention with potential effects on pain, mood, and sleep. This narrative review evaluates the clinical and mechanistic evidence for peripartum esketamine in analgesia, postpartum depressive symptoms, sleep-related outcomes, and maternal-infant safety, with particular attention to the directness and interpretability of the evidence. Most direct clinical evidence derives from cesarean-delivery studies, many of which are single-center trials. Evidence is most consistent for short-term analgesic benefit, whereas opioid-sparing effects are less consistent across individual studies and evidence syntheses. Several randomized trials suggest that low-dose peri-delivery esketamine may reduce early EPDS-defined screen-positive postpartum depressive symptoms, while evidence based on structured diagnostic outcomes remains limited. Evidence for sleep-related benefit remains preliminary and relies predominantly on subjective measures, with no direct postpartum polysomnographic evidence. Studied low-dose regimens have generally shown acceptable short-term maternal and neonatal tolerability in selected populations, but pregnancy-specific pharmacokinetics, lactation, and long-term offspring neurodevelopment remain insufficiently characterized. Overall, esketamine may represent an individualized adjunct in peripartum care, but current evidence does not support its routine prophylactic use. Future multicenter studies should incorporate diagnostic mood outcomes, objective sleep assessment, standardized treatment protocols, and long-term maternal and infant follow-up.
Comparable studies
Other narrative reviews on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. | 2023 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review |