Intranasal Esketamine-dexmedetomidine Combination and Postpartum Depression

NCT07639099 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2026-0287
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postpartum Depression; Parturients; Depressive Symptoms; Esketamine; Dexmedetomidine; Intranasal Administration

Keywords

Parturients; Prenatal depressive symptoms; Esketamine; Dexmedetomidine; Intranasal administration; Postpartum depression

Outcome Measures

Primary Outcomes (1)

• Prevalence of depressive symptoms 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 Outcomes (3)

• Prevalence of depressive symptoms at 7 days postpartum

  At 7 days postpartum

• Treatment response rates at 7 and 42 days postpartum

  At 7 and 42 days postpartum

• Prevalence of major depressive episode at 42 days postpartum

  At 42 days postpartum

Other Outcomes (7)

• Length of hospital stay after giving birth

  Up to 30 days after giving birth

• Time to initiation of breastfeeding

  Up to 3 days after giving birth

• Pain intensity at 1 and 7 days postpartum

  At 1 and 7 days postpartum

Study Arms (2)

Intranasal esketamine-dexmedetomidine

EXPERIMENTAL

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

Intranasal placebo

PLACEBO COMPARATOR

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

Interventions

Placebo DRUG

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).

Also known as: Normal saline

Intranasal placebo

Esketamine-dexmedetomidine combination DRUG

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).

Intranasal esketamine-dexmedetomidine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (28)

• Rodrigues NB, McIntyre RS, Lipsitz O, Lee Y, Cha DS, Shekotikhina M, Vinberg M, Gill H, Subramaniapillai M, Kratiuk K, Lin K, Ho R, Mansur RB, Rosenblat JD. A simplified 6-Item clinician administered dissociative symptom scale (CADSS-6) for monitoring dissociative effects of sub-anesthetic ketamine infusions. J Affect Disord. 2021 Mar 1;282:160-164. doi: 10.1016/j.jad.2020.12.119. Epub 2020 Dec 29.

  PMID: 33418362 BACKGROUND

• Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.

  PMID: 21818162 BACKGROUND

• Chernik DA, Gillings D, Laine H, Hendler J, Silver JM, Davidson AB, Schwam EM, Siegel JL. Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol. 1990 Aug;10(4):244-51.

  PMID: 2286697 BACKGROUND

• Huge V, Lauchart M, Magerl W, Schelling G, Beyer A, Thieme D, Azad SC. Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain. Eur J Pain. 2010 Apr;14(4):387-94. doi: 10.1016/j.ejpain.2009.08.002. Epub 2009 Sep 3.

  PMID: 19733106 BACKGROUND

• Lu X, Tang L, Lan H, Li C, Lin H. A Comparison of Intranasal Dexmedetomidine, Esketamine or a Dexmedetomidine-Esketamine Combination for Induction of Anaesthesia in Children: A Randomized Controlled Double-Blind Trial. Front Pharmacol. 2022 Jan 27;12:808930. doi: 10.3389/fphar.2021.808930. eCollection 2021.

  PMID: 35185548 BACKGROUND

• Li HP, Liu KP, Yao L. Dexmedetomidine in combination with ketamine for pediatric procedural sedation or premedication: A meta-analysis. Am J Emerg Med. 2021 Dec;50:442-448. doi: 10.1016/j.ajem.2021.08.073. Epub 2021 Aug 31.

  PMID: 34492589 BACKGROUND

• Uusalo P, Seppanen SM, Jarvisalo MJ. Feasibility of Intranasal Dexmedetomidine in Treatment of Postoperative Restlessness, Agitation, and Pain in Geriatric Orthopedic Patients. Drugs Aging. 2021 May;38(5):441-450. doi: 10.1007/s40266-021-00846-6. Epub 2021 Mar 16.

  PMID: 33728561 BACKGROUND

• Li A, Yuen VM, Goulay-Dufay S, Sheng Y, Standing JF, Kwok PCL, Leung MKM, Leung AS, Wong ICK, Irwin MG. Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine. Br J Anaesth. 2018 May;120(5):960-968. doi: 10.1016/j.bja.2017.11.100. Epub 2018 Feb 2.

  PMID: 29661413 BACKGROUND

• Jun JH, Kim KN, Kim JY, Song SM. The effects of intranasal dexmedetomidine premedication in children: a systematic review and meta-analysis. Can J Anaesth. 2017 Sep;64(9):947-961. doi: 10.1007/s12630-017-0917-x. Epub 2017 Jun 21.

  PMID: 28639236 BACKGROUND

• Liu Y, Hu Q, Xu S, Li W, Liu J, Han L, Mao H, Cai F, Liu Q, Zhu R, Fang C, Lou Y, Wang Z, Yang H, Wang W. Antidepressant effects of dexmedetomidine compared with ECT in patients with treatment-resistant depression. J Affect Disord. 2024 Feb 15;347:437-444. doi: 10.1016/j.jad.2023.11.077. Epub 2023 Nov 23.

  PMID: 38000472 BACKGROUND

• Zhou Y, Bai Z, Zhang W, Xu S, Feng Y, Li Q, Li L, Ping A, Chen L, Wang S, Duan K. Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jan 2;7(1):e2353252. doi: 10.1001/jamanetworkopen.2023.53252.

  PMID: 38270949 BACKGROUND

• Yu HY, Wang SY, Quan CX, Fang C, Luo SC, Li DY, Zhen SS, Ma JH, Duan KM. Dexmedetomidine Alleviates Postpartum Depressive Symptoms following Cesarean Section in Chinese Women: A Randomized Placebo-Controlled Study. Pharmacotherapy. 2019 Oct;39(10):994-1004. doi: 10.1002/phar.2320. Epub 2019 Sep 15.

  PMID: 31411762 BACKGROUND

• Bosch OG, Dornbierer DA, Bavato F, Quednow BB, Landolt HP, Seifritz E. Dexmedetomidine in Psychiatry: Repurposing of its Fast-Acting Anxiolytic, Analgesic and Sleep Modulating Properties. Pharmacopsychiatry. 2023 Mar;56(2):44-50. doi: 10.1055/a-1970-3453. Epub 2022 Nov 16.

  PMID: 36384232 BACKGROUND

• Keating GM. Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting. Drugs. 2015 Jul;75(10):1119-30. doi: 10.1007/s40265-015-0419-5.

  PMID: 26063213 BACKGROUND

• Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893-913. doi: 10.1007/s40262-017-0507-7.

  PMID: 28105598 BACKGROUND

• Wang S, Deng CM, Zeng Y, Chen XZ, Li AY, Feng SW, Xu LL, Chen L, Yuan HM, Hu H, Yang T, Han T, Zhang HY, Jiang M, Sun XY, Guo HN, Sessler DI, Wang DX. Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ. 2024 Apr 10;385:e078218. doi: 10.1136/bmj-2023-078218.

  PMID: 38808490 BACKGROUND

• Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739.

  PMID: 29282469 BACKGROUND

• Feder A, Parides MK, Murrough JW, Perez AM, Morgan JE, Saxena S, Kirkwood K, Aan Het Rot M, Lapidus KA, Wan LB, Iosifescu D, Charney DS. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.

  PMID: 24740528 BACKGROUND

• Marcantoni WS, Akoumba BS, Wassef M, Mayrand J, Lai H, Richard-Devantoy S, Beauchamp S. A systematic review and meta-analysis of the efficacy of intravenous ketamine infusion for treatment resistant depression: January 2009 - January 2019. J Affect Disord. 2020 Dec 1;277:831-841. doi: 10.1016/j.jad.2020.09.007. Epub 2020 Sep 7.

  PMID: 33065824 BACKGROUND

• Dwyer JB, Landeros-Weisenberger A, Johnson JA, Londono Tobon A, Flores JM, Nasir M, Couloures K, Sanacora G, Bloch MH. Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial. Am J Psychiatry. 2021 Apr 1;178(4):352-362. doi: 10.1176/appi.ajp.2020.20010018. Epub 2021 Mar 3.

  PMID: 33653121 BACKGROUND

• McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, Brietzke E, Dodd S, Gorwood P, Ho R, Iosifescu DV, Lopez Jaramillo C, Kasper S, Kratiuk K, Lee JG, Lee Y, Lui LMW, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA Jr, Stahl S. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry. 2021 May 1;178(5):383-399. doi: 10.1176/appi.ajp.2020.20081251. Epub 2021 Mar 17.

  PMID: 33726522 BACKGROUND

• Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sanchez E, Gutierrez-Rojas L, Meana JJ. Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review. CNS Drugs. 2018 May;32(5):411-420. doi: 10.1007/s40263-018-0519-3.

  PMID: 29736744 BACKGROUND

• Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.

  PMID: 29870457 BACKGROUND

• Latendresse G, Elmore C, Deneris A. Selective Serotonin Reuptake Inhibitors as First-Line Antidepressant Therapy for Perinatal Depression. J Midwifery Womens Health. 2017 May;62(3):317-328. doi: 10.1111/jmwh.12607. Epub 2017 May 9.

  PMID: 28485526 BACKGROUND

• Oyetunji A, Chandra P. Postpartum stress and infant outcome: A review of current literature. Psychiatry Res. 2020 Feb;284:112769. doi: 10.1016/j.psychres.2020.112769. Epub 2020 Jan 9.

  PMID: 31962260 BACKGROUND

• Nisar A, Yin J, Waqas A, Bai X, Wang D, Rahman A, Li X. Prevalence of perinatal depression and its determinants in Mainland China: A systematic review and meta-analysis. J Affect Disord. 2020 Dec 1;277:1022-1037. doi: 10.1016/j.jad.2020.07.046. Epub 2020 Jul 18.

  PMID: 33065811 BACKGROUND

• Howard LM, Molyneaux E, Dennis CL, Rochat T, Stein A, Milgrom J. Non-psychotic mental disorders in the perinatal period. Lancet. 2014 Nov 15;384(9956):1775-88. doi: 10.1016/S0140-6736(14)61276-9. Epub 2014 Nov 14.

  PMID: 25455248 BACKGROUND

• Stewart DE, Vigod S. Postpartum Depression. N Engl J Med. 2016 Dec 1;375(22):2177-2186. doi: 10.1056/NEJMcp1607649. No abstract available.

  PMID: 27959754 BACKGROUND

MeSH Terms

Conditions

Depression; Depression, Postpartum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dong-Xin Wang, MD, PhD

CONTACT

010-83572784; wangdongxin@hotmail.com

Chun-Mei Deng, MD

CONTACT

010-83575085; amychunmei@126.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anaesthesiology

Study Record Dates

• First Submitted: June 4, 2026
• First Posted: June 10, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)