Intranasal Esketamine-dexmedetomidine Combination and Postpartum Depression

June 5, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

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

Esketamine has rapid-onset antidepressant effects and may reduce the risk of postpartum depression in parturients with prenatal depressive symptoms. However, its adverse neuropsychiatric symptoms limits clinical application. Dexmedetomidine can alleviate these adverse symptoms and has independent antidepressant effect. This randomized, double-blind, placebo-controlled trial is designed to evaluate whether intranasal esketamine combined with dexmedetomidine can reduce the prevalence of postpartum depression in women with prenatal depressive symptoms.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

164

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100034
        • Peking University First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pregnant women aged ≥18 years who are preparing for childbirth;
  • Positive prenatal depression screening, defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥5.

Exclusion Criteria:

  • History of schizophrenia or existence of communication barriers;
  • Severe obstetric complications, including severe preeclampsia, placenta accreta, HELLP syndrome, placenta previa, placental abruption, or ASA physical status classification >III;
  • Contraindications to ketamine/esketamine, including refractory hypertension, severe cardiovascular disease (NYHA class ≥III), or hyperthyroidism;
  • Contraindications to dexmedetomidine, including severe bradycardia (heart rate <50 bpm), or second-degree or higher atrioventricular block;
  • Unsuitable for intranasal administration due to nasal cavity diseases (e.g., rhinitis, nasal polyps, or nasal congestion of any cause);
  • Refusal to participate in this study or concurrent participation in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intranasal esketamine-dexmedetomidine

Participants in this arm will receive intranasal administration of dexmedetomidine-esketamine combination.

The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached.

The combination will be administered twice after chilbirth with an interval of 12 hours (2 sessions in total).
Drug: Esketamine-dexmedetomidine combination
The dosage will be calculated based on body weight (approximately 0.4 μg/kg of dexmedetomidine and 0.2 mg/kg of esketamine). The mixture of study drugs will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The combination will be administered twice after delivery with an interval of 12 hours (2 sessions in total).
Placebo Comparator: Intranasal placebo

Participants in this arm will receive intranasal administration of placebo (normal sline).

The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group. The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached.

The placebo will be administered twice after childbirth with an interval of 12 hours (2 sessions in total).
Drug: Placebo
The dosage (volume) will be calculated based on body weight in the same way as that in the intervention group. The placebo (normal saline) will be administered via a nasal spray device, alternating between the two nostrils every 5 minutes, until the target dose is reached. The placebo will be administered twice after delivery with an interval of 12 hours (2 sessions in total).
Other Names:
  • Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of depressive symptoms at 42 days postpartum
Time Frame: At 42 days postpartum
Maternal depression will be assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17; scores range from 0 to 54, with higher scores indicating more severe depressive symptoms) at 42 days postpartum. A HAMD-17 total score ≥8 is defined as presence of at least mild depressive symptoms.
At 42 days postpartum

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of depressive symptoms at 7 days postpartum
Time Frame: At 7 days postpartum
Maternal depression will be assessed using the HAMD-17 at 7 days postpartum at 7 days postpartum. A HAMD-17 total score ≥8 is defined as presence of at least mild depressive symptoms.
At 7 days postpartum
Treatment response rates at 7 and 42 days postpartum
Time Frame: At 7 and 42 days postpartum
Treatment response is defined as a ≥50% reduction in HAMD-17 score from baseline.
At 7 and 42 days postpartum
Prevalence of major depressive episode at 42 days postpartum
Time Frame: At 42 days postpartum
The presence of major depressive episodes will be diagnosed with the the Mini-International Neuropsychiatric Interview version 7.0.2 (MINI 7.0.2), a brief structured diagnostic interview to assess the diagnosis of depression.
At 42 days postpartum

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of hospital stay after giving birth
Time Frame: Up to 30 days after giving birth
Length of hospital stay after giving birth
Up to 30 days after giving birth
Time to initiation of breastfeeding
Time Frame: Up to 3 days after giving birth
Time to initiation of breastfeeding after giving birth
Up to 3 days after giving birth
Pain intensity at 1 and 7 days postpartum
Time Frame: At 1 and 7 days postpartum
Pain intensity will be assessed using the Numeric Rating Scale (NRS; an 11-point scale where 0=no pain and 10=the worst pain), both at rest and with movement.
At 1 and 7 days postpartum
Incidence of persistent pain at 42 days postpartum
Time Frame: At 42 days postpartum
Persistent pain is defined as pain with an NRS pain score ≥1 that persisted since childbirth.
At 42 days postpartum
Proportion of exclusive breastfeeding
Time Frame: At 1, 7, and 42 days postpartum
Proportion of exclusive breastfeeding at 1, 7, and 42 days postpartum
At 1, 7, and 42 days postpartum
Maternal complications within 42 days.
Time Frame: Up to 42 days postpartum
Maternal complications are defined as any medical conditions that required hospital visits and therapeutic intervention.
Up to 42 days postpartum
Neonatal complications within 42 days.
Time Frame: Up to 42 days after birth
Neonatal complications are defined as any medical conditions that required hospital visits and therapeutic intervention.
Up to 42 days after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Investigators

  • Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

October 1, 2029

Study Completion (Estimated)

December 1, 2029

Study Registration Dates

First Submitted

June 4, 2026

First Submitted That Met QC Criteria

June 5, 2026

First Posted (Actual)

June 10, 2026

Study Record Updates

Last Update Posted (Actual)

June 10, 2026

Last Update Submitted That Met QC Criteria

June 5, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0287

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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