Intranasal Esketamine-dexmedetomidine Combination and Postpartum Depression

Summary

Esketamine has rapid-onset antidepressant effects and may reduce 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.

Timeline

Start

2026-06

Primary completion

2029-10

Completion

2029-12

Publications

• Background 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications