Table 3.

Cross-Domain Summary of Evidence for Peripartum Analgesic, Mood-Related, and Sleep-Related Outcomes

Domain and Clinical Question	Principal Evidence Base	Consistency	Directness	Current Interpretation	References
Does esketamine improve short-term post-cesarean analgesia?	RCTs and evidence syntheses	Generally favorable	Predominantly direct	Short-term analgesic benefit is reasonably supported, although effect magnitude varies with regimen, background analgesia, and study design.	[33–47]
Does esketamine reduce post-cesarean opioid exposure?	Individual RCTs and evidence syntheses	Mixed	Predominantly direct	Some individual studies reported lower opioid use or fewer PCIA activations, but opioid-sparing effects are not consistently reproduced across pooled evidence.	[37,41–45]
Is epidural esketamine an effective adjunct for labor analgesia?	Dose-finding and noninferiority studies	Favorable but limited	Direct	Supports neuraxial adjunct activity and local-anesthetic sparing, but does not establish a standardized dose, preferred regimen, or comparator superiority.	[48–51]
Does esketamine reduce EPDS-defined screen-positive postpartum depressive symptoms?	RCTs and substantially overlapping meta-analyses	Generally favorable but heterogeneous	Direct	Several studies suggest an early reduction in screening-defined depressive outcomes, but not all trials are positive, durability is inconsistent, and repeated meta-analyses do not represent independent confirmation.	[7,8,44,45,52,58–78]
Does esketamine prevent clinically diagnosed postpartum depressive episodes?	Limited multicenter randomized evidence	Promising but incompletely replicated	Direct but sparse	One multicenter trial using a structured diagnostic interview showed benefit at 42 days in women with antenatal depressive symptoms; external replication is required before broader inference.	[9]
Does esketamine improve subjective postpartum sleep?	Few obstetric studies using mainly questionnaire-based secondary outcomes	Preliminary	Direct but limited	A possible subjective sleep benefit has been reported, but it cannot be reliably separated from changes in pain, mood, sedation, or cointerventions.	[43,80,85]
Does esketamine improve objective postpartum sleep architecture?	No direct postpartum polysomnographic study	Not established	Indirect	Current evidence does not establish effects on REM sleep, slow-wave sleep, or other objective postpartum sleep-stage parameters.	[26,27,86,87]
What is known about short-term maternal and neonatal tolerability?	RCTs, cohorts, and evidence syntheses	Generally reassuring for studied regimens	Direct for short-term outcomes	Studied low-dose regimens generally show acceptable short-term tolerability, but this should not be interpreted as established long-term maternal or offspring safety.	[7–9,29,39,63,64,75,76]

Abbreviations: PPD, postpartum depression; RCT, randomized controlled trial.