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CompletedNCT03336541Updated Dec 13, 2021

Low-dose Ketamine and Postpartum Depression in Parturients With Prenatal Depression

A Phase 4 interventional study of Ketamine and Placebo in Perinatal Depression, Ketamine and Cesarean Delivery, sponsored by Peking University First Hospital. Completed at 1 site in China. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2021-12-13.

Sponsored by Peking University First Hospital · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
64
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
Female
01

Study summary

Postpartum depression is common in mothers early after childbirth and produces harmful effects not only on mothers, but also on infants and young children. Parturients with prenatal depression are at increased of postpartum depression. Low-dose ketamine can be used for antidepressant therapy. We hypothesize that low-dose ketamine has a therapeutic effect on parturients with prenatal depression. This study is designed to investigate whether low-dose ketamine administered during cesarean delivery can decrease the incidence of postpartum depression in parturients with prenatal depression.

Read the detailed description

Postpartum depression refers to maternal depression developed early after childbirth, with reported incidences varied from 15% to 20%. The development of postpartum depression produces harmful effects not only on mothers, but also on infants and young children. Prenatal depression or high depression score is an independent risk factor for the development of postpartum depression.

Ketamine is commonly used as an general anesthetic. In addition, low-dose ketamine is recommended for antidepressant therapy. We hypothesize that low-dose ketamine has a therapeutic effect on parturients with prenatal depression. However, evidences in this aspect are insufficient. The purpose of this study is to investigate whether low-dose ketamine administered during cesarean delivery can decrease the incidence of postpartum depression in parturients with prenatal depression.

02

Conditions studied

  • Perinatal Depression
  • Ketamine
  • Cesarean Delivery
  • Postpartum Depression

Keywords

  • Prenatal depression
  • Ketamine
  • Cesarean delivery
  • Postpartum depression
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Parturients with age from 18 to 45 years and scheduled for elective cesarean delivery;
  • Prenatal depression score (EPDS) of 10 or higher;
  • Provide written informed consents.

Exclusion criteria

Exclusion Criteria:

  • Refused to participate in the study;
  • History of schizophrenia or other disease that prevent normal communication before delivery;
  • Presence of contraindications to neuraxial anesthesia, including central nervous system diseases (such as poliomyelitis), spinal diseases (such as spinal canal tumor, lumbar disc prolapse, history of spinal trauma), systemic infection (such as sepsis, bacteremia), local infection in the site of puncture, or coagulopathy;
  • Severe complications during pregnancy (such as severe preeclampsia, placenta accreta, HELLP syndrome);
  • Severe comorbidity before pregnancy (such as severe cardiac dysfunction);
  • Scheduled to undergo cesarean delivery under general anesthesia;
  • Other reasons that are considered unsuitable for study participation.
04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
64 participants (actual)

Study arms

  • Experimental
    Ketamine group

    Low-dose ketamine (0.5 mg/kg in 100 ml normal saline) is intravenously infused in 40 minutes after childbirth during cesarean delivery.

    Drug: Ketamine

  • Placebo comparator
    Placebo group

    Placebo (100 ml normal saline) is intravenously infused in 40 minutes after childbirth during cesarean delivery.

    Drug: Placebo

Interventions

  • DrugKetamine

    Ketamine (0.5 mg/kg in 100 ml normal saline) will be administered by intravenous infusion in 40 minutes after childbirth during cesarean delivery.

    Also known as: Ketamine hydrochloride

  • DrugPlacebo

    Placebo (100 ml normal saline) will be administered by intravenous infusion in 40 minutes after childbirth during cesarean delivery.

    Also known as: Normal saline

05

What researchers measure

Primary outcomes

  1. The score of postpartum depression at 48 hous after childbirth.

    Postpartum depression is assessed with Edinburgh postnatal depression scale (EPDS) at 48 hours after childbirth. The EPDS is a 10-item self-rating post-natal depression scale. Each item is scored from 0 to 3, resulting an overall score ranging from 0-30; a high score indicates severe depression.

    Time frame: At 48 hours after delivery.

Secondary outcomes

  1. Time of first breast feeding.

    Time of first breast feeding.

    Time frame: From delivery to 24 hours after delivery.

  2. The proportion of neonates with breast feeding.

    The proportion of neonates with breast feeding.

    Time frame: At 24 hours after delivery.

  3. Duration of neonatal sleep within 24 hours after delivery.

    Duration of neonatal sleep within 24 hours after delivery.

    Time frame: During the first 24 hours after delivery.

  4. Length of stay in hospital after delivery.

    Length of stay in hospital after delivery.

    Time frame: From childbirth up to 30 days after delivery.

  5. The score of postpartum depression at 42 days after delivery.

    Postpartum depression is assessed with EPDS at 42 days after childbirth.

    Time frame: At 42 days after delivery.

  6. Incidence of postpartum depression at 42 days after delivery.

    Postpartum depression is assessed with EPDS at 42 days after childbirth. A EPDS score of 10 or above is defined as postpartum depression.

    Time frame: At 42 days after delivery.

  7. Incidence of maternal complications with 42 days after delivery.

    Incidence of maternal complications with 42 days after delivery.

    Time frame: From childbirth up to 42 days after delivery.

  8. Incidence of neonatal complications with 42 days after delivery.

    Incidence of neonatal complications with 42 days after delivery.

    Time frame: From childbirth up to 42 days after delivery.

06

Study locations

1 site
  • Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital
    Beijing, Beijing 100034, China
07

References and documents

Publications

  • Patel M, Bailey RK, Jabeen S, Ali S, Barker NC, Osiezagha K. Postpartum depression: a review. J Health Care Poor Underserved. 2012 May;23(2):534-42. doi: 10.1353/hpu.2012.0037. PubMed 22643605 ↗
  • Stein A, Pearson RM, Goodman SH, Rapa E, Rahman A, McCallum M, Howard LM, Pariante CM. Effects of perinatal mental disorders on the fetus and child. Lancet. 2014 Nov 15;384(9956):1800-19. doi: 10.1016/S0140-6736(14)61277-0. Epub 2014 Nov 14. PubMed 25455250 ↗
  • Verbeek T, Bockting CL, van Pampus MG, Ormel J, Meijer JL, Hartman CA, Burger H. Postpartum depression predicts offspring mental health problems in adolescence independently of parental lifetime psychopathology. J Affect Disord. 2012 Feb;136(3):948-54. doi: 10.1016/j.jad.2011.08.035. Epub 2011 Sep 17. PubMed 21930302 ↗
  • Feldman R, Granat A, Pariente C, Kanety H, Kuint J, Gilboa-Schechtman E. Maternal depression and anxiety across the postpartum year and infant social engagement, fear regulation, and stress reactivity. J Am Acad Child Adolesc Psychiatry. 2009 Sep;48(9):919-927. doi: 10.1097/CHI.0b013e3181b21651. PubMed 19625979 ↗
  • Kersten-Alvarez LE, Hosman CM, Riksen-Walraven JM, van Doesum KT, Smeekens S, Hoefnagels C. Early school outcomes for children of postpartum depressed mothers: comparison with a community sample. Child Psychiatry Hum Dev. 2012 Apr;43(2):201-18. doi: 10.1007/s10578-011-0257-y. PubMed 22011810 ↗
  • Raposa E, Hammen C, Brennan P, Najman J. The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression. J Adolesc Health. 2014 Jan;54(1):88-93. doi: 10.1016/j.jadohealth.2013.07.038. Epub 2013 Sep 20. PubMed 24060574 ↗
  • Naicker K, Wickham M, Colman I. Timing of first exposure to maternal depression and adolescent emotional disorder in a national Canadian cohort. PLoS One. 2012;7(3):e33422. doi: 10.1371/journal.pone.0033422. Epub 2012 Mar 26. PubMed 22461893 ↗
  • Schiller CE, Meltzer-Brody S, Rubinow DR. The role of reproductive hormones in postpartum depression. CNS Spectr. 2015 Feb;20(1):48-59. doi: 10.1017/S1092852914000480. Epub 2014 Sep 29. PubMed 25263255 ↗
  • Hart AR, Farber KG, Kellner ChH. Postpartum Depression. N Engl J Med. 2017 Mar 2;376(9):895. doi: 10.1056/NEJMc1616547. No abstract available. PubMed 28252268 ↗
  • Kingston D, McDonald S, Austin MP, Tough S. Association between Prenatal and Postnatal Psychological Distress and Toddler Cognitive Development: A Systematic Review. PLoS One. 2015 May 21;10(5):e0126929. doi: 10.1371/journal.pone.0126929. eCollection 2015. PubMed 25996151 ↗
  • Layer RT, Popik P, Olds T, Skolnick P. Antidepressant-like actions of the polyamine site NMDA antagonist, eliprodil (SL-82.0715). Pharmacol Biochem Behav. 1995 Nov;52(3):621-7. doi: 10.1016/0091-3057(95)00155-p. PubMed 8545484 ↗
  • Meloni D, Gambarana C, De Montis MG, Dal Pra P, Taddei I, Tagliamonte A. Dizocilpine antagonizes the effect of chronic imipramine on learned helplessness in rats. Pharmacol Biochem Behav. 1993 Oct;46(2):423-6. doi: 10.1016/0091-3057(93)90374-3. PubMed 7903459 ↗
  • Moryl E, Danysz W, Quack G. Potential antidepressive properties of amantadine, memantine and bifemelane. Pharmacol Toxicol. 1993 Jun;72(6):394-7. doi: 10.1111/j.1600-0773.1993.tb01351.x. PubMed 8361950 ↗
  • Papp M, Moryl E. Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression. Eur J Pharmacol. 1994 Sep 22;263(1-2):1-7. doi: 10.1016/0014-2999(94)90516-9. PubMed 7821340 ↗
  • Przegalinski E, Tatarczynska E, Deren-Wesolek A, Chojnacka-Wojcik E. Antidepressant-like effects of a partial agonist at strychnine-insensitive glycine receptors and a competitive NMDA receptor antagonist. Neuropharmacology. 1997 Jan;36(1):31-7. doi: 10.1016/s0028-3908(96)00157-8. PubMed 9144639 ↗
  • Trullas R, Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990 Aug 21;185(1):1-10. doi: 10.1016/0014-2999(90)90204-j. PubMed 2171955 ↗
  • Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004 Jul;61(7):705-13. doi: 10.1001/archpsyc.61.7.705. PubMed 15237082 ↗
  • Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008 May;7(5):426-37. doi: 10.1038/nrd2462. PubMed 18425072 ↗
  • McCullumsmith RE, Kristiansen LV, Beneyto M, Scarr E, Dean B, Meador-Woodruff JH. Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res. 2007 Jan 5;1127(1):108-18. doi: 10.1016/j.brainres.2006.09.011. Epub 2006 Nov 17. PubMed 17113057 ↗
  • Paul IA, Nowak G, Layer RT, Popik P, Skolnick P. Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments. J Pharmacol Exp Ther. 1994 Apr;269(1):95-102. PubMed 8169857 ↗
  • Boyer PA, Skolnick P, Fossom LH. Chronic administration of imipramine and citalopram alters the expression of NMDA receptor subunit mRNAs in mouse brain. A quantitative in situ hybridization study. J Mol Neurosci. 1998 Jun;10(3):219-33. doi: 10.1007/BF02761776. PubMed 9770644 ↗
  • Aan Het Rot M, Zarate CA Jr, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry. 2012 Oct 1;72(7):537-47. doi: 10.1016/j.biopsych.2012.05.003. Epub 2012 Jun 16. PubMed 22705040 ↗
  • DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010 Dec;71(12):1605-11. doi: 10.4088/JCP.09m05327blu. Epub 2010 Jul 13. PubMed 20673547 ↗
  • Katalinic N, Lai R, Somogyi A, Mitchell PB, Glue P, Loo CK. Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Aust N Z J Psychiatry. 2013 Aug;47(8):710-27. doi: 10.1177/0004867413486842. Epub 2013 May 9. PubMed 23661785 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03336541
Lead sponsor
Peking University First Hospital
Responsible party
Dong-Xin Wang (Professor and Chairman, Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital) — Principal investigator
First posted
Nov 8, 2017
Start date
Nov 23, 2017
Primary completion
May 14, 2018
Completion
Jun 25, 2018
Last update
Dec 13, 2021

Study contacts

Dong-Xin Wang, MD, PhD
principal investigator · Peking University First Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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