Scientists recently found that a single dose of 0.2 mg/kg of esketamine soon after childbirth reduced major depressive events among women with prenatal depressive symptoms by almost three-quarters at 42 days’ postpartum, but say more studies are needed to see if the benefits last longer.
Perinatal depression is common, particularly in low-income nations, with negative consequences for both mother and child – the moms frequently feeling anxiety, weaker connections, and lower attachment, and their children being more likely to have behavioural and emotional issues, as well as long-term psychological and developmental disorders.
Poor physical health, a lack of social support, a low socio-economic level, insufficient education, and a history of violent exposure are all risk factors for prenatal depression, which is also a primary predictor of postnatal depression, and which occasionally requires pharmacological therapies.
Esketamine, a rapid-onset antidepressant, offers potential advantages for treatment-resistant depression, but its effect on women with perinatal depression is unknown, reports News-Medical.net. Previous studies have mainly focused on Caesarean births, omitting mothers who are depressed or at high risk of developing depression after delivery.
About the study
In the present randomised, placebo-controlled, double-blinded, controlled trial, published in The BMJ, researchers evaluated whether low-dose esketamine administered immediately after birth lowers depression in moms suffering from prenatal depression for 42 days.
The researchers conducted the trial at five hospitals across China between 19 June 2020 and 3 August 2022. They included pregnant women aged 18 and above with mild, moderate, or severe prenatal depression (defined as Edinburgh postnatal depression scale [EPDS] scores equal to or above 10) hospitalised for delivery.
They excluded women with pre-pregnancy mood disorders, severe pregnancy complications, physical status 3 or higher, or contraindications to ketamine or esketamine use, such as severe cardiovascular disease, refractory hypertension, or hyperthyroidism.
Exclusion criteria included American Society of Anaesthesiologists (ASA) physical status 3 or higher.
The researchers randomised the individuals in a 1:1 ratio to the esketamine group (0.20 mg per kg body weight) or placebo group, with drugs administered intravenously during the initial 40 minutes post-delivery while clipping the birth cord.
The primary research outcomes were major depressive events after 42 days of delivery, identified using mini-international neuropsychiatric interviews.
Secondary study outcomes included EPDS scores on days one and 42 after childbirth and the Hamilton Depression Rating Scale (HDRS) score 42 days after delivery. The researchers monitored adverse occurrences until 24 hours after delivery. They used logistic regression to determine the relative risk (RR) values. They used imputed missing primary outcome data in post-hoc sensitivity analyses.
The researchers measured anxiety using the Zung self-rating anxiety scale, social assistance using the social support rating scale, marital satisfaction using the ENRICH (evaluation and nurturing relationship issues, communication, and happiness) scale, and agitation-sedation using the Richmond agitation-sedation scale.
Maternal data included epidural analgesia acceptance, delivery style, fluid infusion, and blood loss, as well as the use of additional analgesics and sedatives. Body weight, sex, Apgar scores at one and five minutes after delivery, and initial destination were all recorded.
Results
The researchers screened 14 243 women and randomly assigned 364 to the study groups. The average participation age was 32 years. After 42 days, 12 (6.7%) esketamine recipients and 46 (25%) placebo recipients experienced a severe depressive episode (RR 0.3). After accounting for missing data, 14 (7.7%) of esketamine recipients and 46 (25%) of placebo recipients experienced severe depressive episodes (RR 0.3). The protocol analysis yielded comparable results.
Esketamine-treated women had lower EPDS scores on day seven and day 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4).
Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.
Esketamine-treated women had lower EPDS scores on day seven and 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4). Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.
Overall, the study found that a single modest dosage of 0.2 mg/kg of esketamine administered soon after childbirth reduces major depressive events among women with prenatal depressive symptoms by almost three-quarters at 42 days postpartum.
Esketamine increased the frequency of neuropsychiatric symptoms, but they were brief and lasted <24 hours, requiring no medication.
The antidepressant effect of low-dose esketamine appears to continue longer in women with prenatal depression than in the overall population with depression. Further analysis is required to establish whether the reaction continues after 42 days.
Study details
Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial
Shuo Wang, Daniel Sessler, Dong-Xin Wang et al.
Published in The BMJ on 27 February 2024
Abstract
Objective
To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression.
Design
Randomised, double blind, placebo controlled trial with two parallel arms.
Setting
Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022.
Participants
A total of 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery.
Interventions
Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped.
Main outcome measures
The primary outcome was prevalence of a major depressive episode at 42 days’ post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days’ post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth.
Results
A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference −3, 95% CI −4 to −2; P<0.001) and 42 days (−3, −4 to −2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (−4, −6 to −3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment.
Conclusions
For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days’ post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention.
See more from MedicalBrief archives:
Perinatal depression: mums, dads, babies all at risk – London meta-analysis
Misinformation on postpartum depression ‘risks lives’
Depression during and after pregnancy needs more attention, says obstetrician
SA moves to treat depression with psychedelics