Impact of Intranasal Esketamine-dexmedetomidine Combination on Postpartum Depression in Parturients With Prenatal Depressive Symptoms: a Randomized, Double-blind, and Placebo-controlled Trial

Perinatal depression is a common mental disorder in women during the perinatal period. Many studies have shown that existence of prenatal depressive symptoms is an important risk factor of postpartum depression. Early identification of pregnant women with symptoms of prenatal depression, and providing appropriate interventions may play important roles in reducing the incidence of postpartum depression.

Ketamine is an NMDA-receptor antagonist. Esketamine, the S-enantiomer of ketamine, has a higher affinity for the NMDA receptor and is approximately twice as potent as ketamine in anesthesia and analgesia. Recent studies have demonstrated that ketamine and esketamine have marked rapid-acting antidepressant effects, but often accompanied by neuropsychiatric adverse effects, including dizziness, hallucinations, nightmares, and dissociative symptoms. Intranasal esketamine is approved for treatment-resistant depression.

Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, is commonly used as a perioperative adjuvant. Recently, its potential role in psychiatric disorders has drawn increasing attention, with evidence suggesting preventive and therapeutic effects on anxiety, depression, and post-traumatic stress disorder. Intranasal dexmedetomidine has been safely used in both adults and children, particularly for procedural sedation and preoperative administration.

Combined use of esketamine with dexmedetomidine has been shown to reduce the neuropsychiatric adverse effects associated with esketamine alone, while also exhibiting synergistic sedative and analgesic effects. The investigators suppose that, for pregnant women with prenatal depressive symptoms, intranasal administration of a low-dose esketamine-dexmedetomidine combination after childbirth may reduce the incidence of postpartum depression with fewer neuropsychiatric side effects.

This randomized controlled trial is designed to investigate the effect of intranasal esketamine-dexmedetomidine combination administered after childbirth on the incidence of postpartum depression among paturients with prenatal depressive symptoms.