Effect of Low-dose Esketamine on Maternal Depression at 2 Years After Childbirth

Sponsor

Peking University First Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05698394

Collaborator

(none)

364

Enrollment

Locations

Arms

52.4

Anticipated Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Postpartum depression refers to the depression after childbirth, which is a common mental disorder in women. The pathogenesis of postpartum depression is not fully understood, and may be related to a variety of factors. Prenatal depression is an important risk factor for postpartum depression. Our recent multicenter randomized controlled trial, "Effect of Low-dose esketamine on the incidence of postpartum depression in women with prenatal depression", explored the effect of immediate postpartum intravenous infusion of low-dose esketamine on the incidence of postpartum depression in women with prenatal depression. The preliminary results showed that it reduced the incidence of postpartum depression at 42 days. Since there were no studies on the effect of intravenous esketamine infusion after delivery on long-term postpartum depression, this study is a long-term follow-up of the previous randomized trial. We aim to explore the effect of low-dose intravenous esketamine after delivery on the incidence of 2-year maternal depression after delivery in women with prenatal depressive symptoms.

Condition or Disease	Intervention/Treatment	Phase
Prenatal Depression Ketamine Postpartum Depression	Drug: Esketamine Drug: Placebo	Phase 4

Detailed Description

Postpartum depression refers to the depression after childbirth. It is a common mental disorder after childbirth. In recent years, it has attracted more and more public attention. Studies have reported an incidence of postpartum depression ranging from 10% to 29%. Our previous findings showed that the incidence of depression at 42 days postpartum was 24.3%. Postpartum depression has adverse effects on physical and mental health of women, but also may have adverse influences on offspring including nutrition health, and cognitive and behavioral development. The pathogenesis of postpartum depression is not completely clear, and may be related to many factors, such as hormone level changes after childbirth, psychosocial factors, and adverse obstetric factors. Plently of studies have shown that prenatal depression is an important risk factor for postpartum depression. One meta-analysis showed that the incidence of postnatal depression could be as high as 39% in people with prenatal depression. Therefore, it is possible to reduce the occurrence of postpartum depression by active intervention of prenatal depressed parturients.

Ketamine, an NMDA-receptor antagonist, is a classic analgesic drug with advantages of light respiratory and circulatory inhibition and good analgesic effect. Recently, it has been found to have antidepressant effect and has been widely used in the field of psychiatry. Esketamine, a S-enantiomer of racemic ketamine, has similar antidepressant effects to equivalent doses of ketamine, with a lower incidence of adverse reactions. In 2019, esketamine was approved by the US FDA for the treatment of treatment-resistant depression. At present, the results of studies on the use of esketamine in the perioperative period for the prevention and treatment of postoperative or postpartum depression are mixed.

Our recent multicenter randomized controlled trial, "Effect of low-dose esketamine on the incidence of postpartum depression in women with prenatal depression", explored the effect of immediate postpartum intravenous administration of low-dose esketamine on the incidence of postpartum depression in women with prenatal depression. The multicenter study included 364 women who were given a low dose of esketamine intravenously after delivery. Preliminary results show that it can reduce the incidence of postpartum depression at 42 days. Here we conduct a 2-year follow-up of the women enrolled in the underlying trial to figure out the occurrence of 2-year maternal depression, and to explore the effect of immediate intravenous infusion of low-dose esketamine on the incidence of chronic depression at 2 years postpartum.

Study Design

Study Type:

Interventional

Actual Enrollment :

364 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel AssignmentParallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Effect of Intravenous Low-dose Esketamine on Maternal Depression at 2 Years After Childbirth in Women With Prenatal Depression: 2-year Follow-up of a Randomized Controlled Trial

Actual Study Start Date :

Jun 19, 2020

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Esketamine group For women in this group, study drug (esketamine 0.2 mg/kg in 20 ml normal saline) will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth.	Drug: Esketamine 0.2 mg/kg S-ketamine in 20 ml normal saline will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth
Placebo Comparator: placebo group For women in this group, study drug (20 ml normal saline) will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth.	Drug: Placebo 20 ml normal saline will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth. Other Names: normal saline 0.9% sodium chloride

Arm

Intervention/Treatment

Experimental: Esketamine group

For women in this group, study drug (esketamine 0.2 mg/kg in 20 ml normal saline) will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth.

Drug: Esketamine

0.2 mg/kg S-ketamine in 20 ml normal saline will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth

Placebo Comparator: placebo group

For women in this group, study drug (20 ml normal saline) will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth.

Drug: Placebo

20 ml normal saline will be infused at a rate of 30 ml/h (infusion finished in 40 minutes) after giving birth.

Other Names:

normal saline

0.9% sodium chloride

Outcome Measures

Primary Outcome Measures

Incidence maternal depression at 2 years postpartum [At 2 years postpartum (24-30 months)]
Incidence of depression in women at 2 years postpartum. Diagnosis was made according to M.I.N.I. 6.0.

Secondary Outcome Measures

PHQ-9 scores and incidence of moderate-severe depression in women at 2 years postpartum. [At 2 years postpartum (24-30 months)]
PHQ-9 score and moderate-severe depression (PHQ-9 score ≥10) in women at 2 years postpartum.
Incidence of chronic pain in women at 2 years postpartum [At 2 years postpartum (24-30 months)]
Incidence of chronic pain in women at 2 years postpartum
Incidence of developmental delay in offspring at 2 years of age [At 2 years postpartum (24-30 months)]
Incidence of developmental delay in offspring at 2 years of age measured by the Ages & Stages Questionnaires 3rd edition (ASQ-3) in Chinese

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

All 364 pregnant women who participated in the underling trial "Effect of low-dose esketamine on the incidence of postpartum depression in women with prenatal depression: a randomized, double-blind, placebo-controlled trial" NCT04414943）and agreed to accept this 2-year follow-up.

The inclusion criteria of the underlying trial:

Maternal age ≥18 years;
Prenatal Edinburgh postnatal depression scale score ≥10 points.

Exclusion Criteria of the previous study:

A clear history of mental illness (depression, schizophrenia, etc.) or communication disorders
Severe pregnancy complications (such as severe preeclampsia, placenta accreta, HELLP syndrome, placenta previa, placenta abruption) before surgery;
ASA grade ≥III;
The presence of contraindications to ketamine/esketamine use (e.g., stubborn, refractory hypertension, severe cardiovascular disease [cardiac function grade ≥III], hyperthyroidism).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hunan Provincial Maternal and Child Health Care Hospital	Changsha	Hunan	China
2	Women's Hospital of Nanjing Medical University	Nanjing	Jiangsu	China
3	Women's Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang	China
4	Peking University First Hospital	Beijing		China	100034