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出境医 / 临床实验 / Low-dose S-Ketamine and Postpartum Depression in Parturients With Prenatal Depression

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

Study Description
Brief 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 risk of postpartum depression. Low-dose s-ketamine can be used for antidepressant therapy. We hypothesize that low-dose s-ketamine has a therapeutic effect on parturients with prenatal depression. This study is designed to investigate whether low-dose s-ketamine administered after childbirth can reduce the incidence of postpartum depression in parturients with prenatal depression.

Condition or disease Intervention/treatment Phase
Perinatal Depression Ketamine Postpartum Depression Drug: S-ketamine Drug: Placebo Not Applicable

Detailed Description:

Postpartum depression refers to maternal depression developed early after childbirth, with reported incidences varied from 10% 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 a commonly used general anesthetic. In addition, low-dose ketamine is recommended for antidepressant therapy. S-ketamine is more potent as an anaesthetic and might also have a better antidepressive effect. We hypothesize that low-dose s-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 s-ketamine administered after childbirth can reduce the incidence of postpartum depression in parturients with prenatal depression.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 364 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effects of Low-dose S-Ketamine on Incidence of Postpartum Depression in Parturients With Prenatal Depression: A Randomized, Double-blind, Placebo-controlled Trial
Actual Study Start Date : June 19, 2020
Estimated Primary Completion Date : May 2021
Estimated Study Completion Date : June 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: S-katamine group
Low-dose s-ketamine (0.2 mg/kg in 20 ml normal saline) is intravenously infused in 40 minutes after childbirth.
 Drug: S-ketamine
S-ketamine (0.2 mg/kg in 20 ml normal saline) is administered by intravenous infusion in 40 minutes after childbirth.
Other Name: S-ketamine hydrochloride
Placebo Comparator: Placebo group
Placebo (20 ml normal saline) is intravenously infused in 40 minutes after childbirth.
 Drug: Placebo
Placebo (20 ml normal saline) is administered by intravenous infusion in 40 minutes after childbirth.
Other Name: Normal saline
Outcome Measures
Primary Outcome Measures :
  1. The incidence of depression at 42 days after childbirth. [ Time Frame: At 42 days after childbirth. ]
    Postpartum depression at 42 days is diagnosed by using the Mini-International Neuropsychiatric Interview-Version 6.0 (MINI-V6.0) by a psychiatrist.


Secondary Outcome Measures :
  1. The score of depression at 7 and 42 days after childbirth. [ Time Frame: At 7 and 42 days after childbirth. ]
    The score of depression at 7 and 42 days after childbirth is assessed by using the Edinburgh Postpartum Depression Scale (EPDS). This is a 10-item self-report questionnaire; each item is rated from 0 to 3 denoting the increasing severity of symptoms, resulting in a total score range from 0 to 30, with higher score indicating more severe depression.

  2. The score of pain at 1, 7 and 42 days after childbirth. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The score of pain at 1, 7 and 42 days after childbirth is assessed by using a Numeric Rating Scale (an 11-point scale where 0 indicates no pain and 10 the worst pain).

  3. The proportion of neonates with breast-feeding. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The proportion of neonates with breast-feeding.

  4. The incidence of postpartum complications within 42 days after childbirth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of postpartum complications within 42 days after childbirth.

  5. The incidence of neonatal disease within 42 days after birth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of neonatal disease within 42 days after birth.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Parturients with age ≥18 years;
  • Presence of prenatal depression (EPDS score ≥10);
  • Provide written informed consents.

Exclusion Criteria:

  • History of psychiatric disease (schizophrenia) or communication barriers that prevent normal communication before childbirth;
  • Severe complications during pregnancy (such as severe preeclampsia, placenta accreta, or HELLP [Hemolysis, Elevated Liver enzymes and Low Platelets] syndrome);
  • ASA physical status classification ≥III;
  • Presence of contraindications to ketamine, including refractory hypertension, severe cardiovascular disease (heart function classification ≥III), or hyperthyroidism;
  • Refuse to participate.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Dong-Xin Wang, MD, PhD 8610 83572784 wangdongxin@hotmail.com
Contact: Yuan Zeng, MD 8610 83572460 yuan_zeng@sina.com

Locations
Layout table for location information
China, Beijing
Peking University First Hospital Recruiting
Beijing, Beijing, China, 100034
Contact: Dong-Xin Wang, MD, PhD    861083572784    wangdongxin@hotmail.com   
Contact: Yuan Zeng, MD    861083572460    yuan_zeng@sina.com   
Sponsors and Collaborators
Peking University First Hospital
Investigators
Layout table for investigator information
Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hospital
Tracking Information
First Submitted Date  ICMJE April 23, 2019
First Posted Date  ICMJE April 25, 2019
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE June 19, 2020
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2020) 		The incidence of depression at 42 days after childbirth. [ Time Frame: At 42 days after childbirth. ]
Postpartum depression at 42 days is diagnosed by using the Mini-International Neuropsychiatric Interview-Version 6.0 (MINI-V6.0) by a psychiatrist.
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2019) 		The incidence of depression at 42 days after childbirth. [ Time Frame: At 42 days after childbirth. ]
Postpartum depression at 42 days is diagnosed by using the Mini-International Neuropsychiatric Interview-Version 6.0, MINI-V6.0) by a psychiatrist.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2019)
  • The score of depression at 7 and 42 days after childbirth. [ Time Frame: At 7 and 42 days after childbirth. ]
    The score of depression at 7 and 42 days after childbirth is assessed by using the Edinburgh Postpartum Depression Scale (EPDS). This is a 10-item self-report questionnaire; each item is rated from 0 to 3 denoting the increasing severity of symptoms, resulting in a total score range from 0 to 30, with higher score indicating more severe depression.
  • The score of pain at 1, 7 and 42 days after childbirth. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The score of pain at 1, 7 and 42 days after childbirth is assessed by using a Numeric Rating Scale (an 11-point scale where 0 indicates no pain and 10 the worst pain).
  • The proportion of neonates with breast-feeding. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The proportion of neonates with breast-feeding.
  • The incidence of postpartum complications within 42 days after childbirth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of postpartum complications within 42 days after childbirth.
  • The incidence of neonatal disease within 42 days after birth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of neonatal disease within 42 days after birth.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 23, 2019)
  • The score of depression at 7 and 42 days after childbirth. [ Time Frame: At 7 and 42 days after childbirth. ]
    The score of depression at 7 and 42 days after childbirth is assessed by using the Edinburgh Postpartum Depression Scale (EPDS).
  • The score of pain at 1, 7 and 42 days after childbirth. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The score of pain at 1, 7 and 42 days after childbirth is assessed by using a Numeric Rating Scale (an 11-point scale where 0 indicates no pain and 10 the worst pain).
  • The proportion of neonates with breast-feeding. [ Time Frame: At 1, 7 and 42 days after childbirth. ]
    The proportion of neonates with breast-feeding.
  • The incidence of postpartum complications within 42 days after childbirth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of postpartum complications within 42 days after childbirth.
  • The incidence of neonatal disease within 42 days after birth. [ Time Frame: Up to 42 days after childbirth. ]
    The incidence of neonatal disease within 42 days after birth.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Low-dose S-Ketamine and Postpartum Depression in Parturients With Prenatal Depression
Official Title  ICMJE Effects of Low-dose S-Ketamine on Incidence of Postpartum Depression in Parturients With Prenatal Depression: A Randomized, Double-blind, Placebo-controlled Trial
Brief 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 risk of postpartum depression. Low-dose s-ketamine can be used for antidepressant therapy. We hypothesize that low-dose s-ketamine has a therapeutic effect on parturients with prenatal depression. This study is designed to investigate whether low-dose s-ketamine administered after childbirth can reduce the incidence of postpartum depression in parturients with prenatal depression.
Detailed Description

Postpartum depression refers to maternal depression developed early after childbirth, with reported incidences varied from 10% 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 a commonly used general anesthetic. In addition, low-dose ketamine is recommended for antidepressant therapy. S-ketamine is more potent as an anaesthetic and might also have a better antidepressive effect. We hypothesize that low-dose s-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 s-ketamine administered after childbirth can reduce the incidence of postpartum depression in parturients with prenatal depression.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Perinatal Depression
  • Ketamine
  • Postpartum Depression
Intervention  ICMJE
  • Drug: S-ketamine
    S-ketamine (0.2 mg/kg in 20 ml normal saline) is administered by intravenous infusion in 40 minutes after childbirth.
    Other Name: S-ketamine hydrochloride
  • Drug: Placebo
    Placebo (20 ml normal saline) is administered by intravenous infusion in 40 minutes after childbirth.
    Other Name: Normal saline
Study Arms  ICMJE
  • Experimental: S-katamine group
    Low-dose s-ketamine (0.2 mg/kg in 20 ml normal saline) is intravenously infused in 40 minutes after childbirth.
    Intervention: Drug: S-ketamine
  • Placebo Comparator: Placebo group
    Placebo (20 ml normal saline) is intravenously infused in 40 minutes after childbirth.
    Intervention: Drug: Placebo
Publications *
  • Nonacs R, Cohen LS. Postpartum mood disorders: diagnosis and treatment guidelines. J Clin Psychiatry. 1998;59 Suppl 2:34-40. Review.
  • Kim S, Soeken TA, Cromer SJ, Martinez SR, Hardy LR, Strathearn L. Oxytocin and postpartum depression: delivering on what's known and what's not. Brain Res. 2014 Sep 11;1580:219-32. doi: 10.1016/j.brainres.2013.11.009. Epub 2013 Nov 14. Review.
  • Giallo R, Pilkington P, McDonald E, Gartland D, Woolhouse H, Brown S. Physical, sexual and social health factors associated with the trajectories of maternal depressive symptoms from pregnancy to 4 years postpartum. Soc Psychiatry Psychiatr Epidemiol. 2017 Jul;52(7):815-828. doi: 10.1007/s00127-017-1387-8. Epub 2017 Apr 27.
  • Giallo R, Cooklin A, Nicholson JM. Risk factors associated with trajectories of mothers' depressive symptoms across the early parenting period: an Australian population-based longitudinal study. Arch Womens Ment Health. 2014 Apr;17(2):115-25. doi: 10.1007/s00737-014-0411-1. Epub 2014 Jan 15.
  • Sutter-Dallay AL, Cosnefroy O, Glatigny-Dallay E, Verdoux H, Rascle N. Evolution of perinatal depressive symptoms from pregnancy to two years postpartum in a low-risk sample: the MATQUID cohort. J Affect Disord. 2012 Jun;139(1):23-9. doi: 10.1016/j.jad.2011.08.018. Epub 2012 Mar 11.
  • McCall-Hosenfeld JS, Phiri K, Schaefer E, Zhu J, Kjerulff K. Trajectories of Depressive Symptoms Throughout the Peri- and Postpartum Period: Results from the First Baby Study. J Womens Health (Larchmt). 2016 Nov;25(11):1112-1121. Epub 2016 Jun 16.
  • Tsai R, Schaffir J. Effect of depot medroxyprogesterone acetate on postpartum depression. Contraception. 2010 Aug;82(2):174-7. doi: 10.1016/j.contraception.2010.03.004. Epub 2010 Apr 13.
  • Ding T, Wang DX, Qu Y, Chen Q, Zhu SN. Epidural labor analgesia is associated with a decreased risk of postpartum depression: a prospective cohort study. Anesth Analg. 2014 Aug;119(2):383-92. doi: 10.1213/ANE.0000000000000107.
  • Quevedo LA, Silva RA, Godoy R, Jansen K, Matos MB, Tavares Pinheiro KA, Pinheiro RT. The impact of maternal post-partum depression on the language development of children at 12 months. Child Care Health Dev. 2012 May;38(3):420-4. doi: 10.1111/j.1365-2214.2011.01251.x. Epub 2011 Jun 8.
  • Parsons CE, Young KS, Rochat TJ, Kringelbach ML, Stein A. Postnatal depression and its effects on child development: a review of evidence from low- and middle-income countries. Br Med Bull. 2012;101:57-79. doi: 10.1093/bmb/ldr047. Epub 2011 Nov 29. Review.
  • Weitzman M, Rosenthal DG, Liu YH. Paternal depressive symptoms and child behavioral or emotional problems in the United States. Pediatrics. 2011 Dec;128(6):1126-34. doi: 10.1542/peds.2010-3034. Epub 2011 Nov 7.
  • Demontigny F, Girard ME, Lacharité C, Dubeau D, Devault A. Psychosocial factors associated with paternal postnatal depression. J Affect Disord. 2013 Aug 15;150(1):44-9. doi: 10.1016/j.jad.2013.01.048. Epub 2013 Mar 13.
  • Dietz LJ, Jennings KD, Kelley SA, Marshal M. Maternal depression, paternal psychopathology, and toddlers' behavior problems. J Clin Child Adolesc Psychol. 2009 Jan;38(1):48-61. doi: 10.1080/15374410802575362.
  • Pawlby S, Sharp D, Hay D, O'Keane V. Postnatal depression and child outcome at 11 years: the importance of accurate diagnosis. J Affect Disord. 2008 Apr;107(1-3):241-5. Epub 2007 Sep 12.
  • Robertson E, Grace S, Wallington T, Stewart DE. Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry. 2004 Jul-Aug;26(4):289-95. Review.
  • Klainin P, Arthur DG. Postpartum depression in Asian cultures: a literature review. Int J Nurs Stud. 2009 Oct;46(10):1355-73. doi: 10.1016/j.ijnurstu.2009.02.012. Epub 2009 Mar 26. Review.
  • Eisenach JC, Pan PH, Smiley R, Lavand'homme P, Landau R, Houle TT. Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression. Pain. 2008 Nov 15;140(1):87-94. doi: 10.1016/j.pain.2008.07.011. Epub 2008 Sep 24.
  • Lee DT, Yip AS, Leung TY, Chung TK. Identifying women at risk of postnatal depression: prospective longitudinal study. Hong Kong Med J. 2000 Dec;6(4):349-54.
  • Jardri R, Pelta J, Maron M, Thomas P, Delion P, Codaccioni X, Goudemand M. Predictive validation study of the Edinburgh Postnatal Depression Scale in the first week after delivery and risk analysis for postnatal depression. J Affect Disord. 2006 Jul;93(1-3):169-76. Epub 2006 Apr 27.
  • Milgrom J, Gemmill AW, Bilszta JL, Hayes B, Barnett B, Brooks J, Ericksen J, Ellwood D, Buist A. Antenatal risk factors for postnatal depression: a large prospective study. J Affect Disord. 2008 May;108(1-2):147-57. Epub 2007 Dec 18.
  • Dennis CL. Can we identify mothers at risk for postpartum depression in the immediate postpartum period using the Edinburgh Postnatal Depression Scale? J Affect Disord. 2004 Feb;78(2):163-9.
  • Huynh NN, McIntyre RS. What Are the Implications of the STAR*D Trial for Primary Care? A Review and Synthesis. Prim Care Companion J Clin Psychiatry. 2008;10(2):91-6.
  • Schwartz J, Murrough JW, Iosifescu DV. Ketamine for treatment-resistant depression: recent developments and clinical applications. Evid Based Ment Health. 2016 May;19(2):35-8. doi: 10.1136/eb-2016-102355. Epub 2016 Apr 6. Review.
  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4.
  • Abdallah CG, Adams TG, Kelmendi B, Esterlis I, Sanacora G, Krystal JH. KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID-ACTING ANTIDEPRESSANTS. Depress Anxiety. 2016 Aug;33(8):689-97. doi: 10.1002/da.22501. Epub 2016 Apr 6. Review.
  • Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950-66. doi: 10.1176/appi.ajp.2015.15040465. Review.
  • Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med. 2016 May;46(7):1459-72. doi: 10.1017/S0033291716000064. Epub 2016 Feb 12.
  • Drewniany E, Han J, Hancock C, Jones RL, Lim J, Nemat Gorgani N, Sperry JK 3rd, Yu HJ, Raffa RB. Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression. J Clin Pharm Ther. 2015 Apr;40(2):125-30. doi: 10.1111/jcpt.12238. Epub 2014 Dec 26.
  • Strasburger SE, Bhimani PM, Kaabe JH, Krysiak JT, Nanchanatt DL, Nguyen TN, Pough KA, Prince TA, Ramsey NS, Savsani KH, Scandlen L, Cavaretta MJ, Raffa RB. What is the mechanism of Ketamine's rapid-onset antidepressant effect? A concise overview of the surprisingly large number of possibilities. J Clin Pharm Ther. 2017 Apr;42(2):147-154. doi: 10.1111/jcpt.12497. Epub 2017 Jan 22. Review.
  • Fond G, Loundou A, Rabu C, Macgregor A, Lançon C, Brittner M, Micoulaud-Franchi JA, Richieri R, Courtet P, Abbar M, Roger M, Leboyer M, Boyer L. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl). 2014 Sep;231(18):3663-76. doi: 10.1007/s00213-014-3664-5. Epub 2014 Jul 20. Review.
  • Park M, Niciu MJ, Zarate CA Jr. Novel Glutamatergic Treatments for Severe Mood Disorders. Curr Behav Neurosci Rep. 2015 Dec;2(4):198-208. Epub 2015 Oct 9.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 23, 2019) 		364
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Parturients with age ≥18 years;
  • Presence of prenatal depression (EPDS score ≥10);
  • Provide written informed consents.

Exclusion Criteria:

  • History of psychiatric disease (schizophrenia) or communication barriers that prevent normal communication before childbirth;
  • Severe complications during pregnancy (such as severe preeclampsia, placenta accreta, or HELLP [Hemolysis, Elevated Liver enzymes and Low Platelets] syndrome);
  • ASA physical status classification ≥III;
  • Presence of contraindications to ketamine, including refractory hypertension, severe cardiovascular disease (heart function classification ≥III), or hyperthyroidism;
  • Refuse to participate.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dong-Xin Wang, MD, PhD 8610 83572784 wangdongxin@hotmail.com
Contact: Yuan Zeng, MD 8610 83572460 yuan_zeng@sina.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03927378
Other Study ID Numbers  ICMJE 2018[224]
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dong-Xin Wang, Peking University First Hospital
Study Sponsor  ICMJE Peking University First Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dong-Xin Wang, MD, PhD Peking University First Hospital
PRS Account Peking University First Hospital
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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