Peripartum Esketamine: A Narrative Review of Analgesia, Postpartum Depressive Symptoms, Sleep-Related Outcomes, and Safety.

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.