Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial

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 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)v22.0% (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. Trial registration ClinicalTrials.govNCT04414943.

The association between epidural labour analgesia and postpartum depression

“…The Edinburgh Postnatal Depression Scale is designed for screening rather than diagnosis, and the cut-off score of ≥ 10 lacks specificity for diagnosing perinatal depression compared with reference standards [4]. Using the Brief International Neuropsychiatric Interview [2] for depression assessment may provide more reliable results.…”

“…Although the study documented and compared the personal and family history of psychiatric conditions in participants, it did not assess the current antenatal mental status of the women near delivery. Recently, research by Wang et al suggests that the prevalence of mild or higher levels of antenatal depression (Edinburgh Postnatal Depression Scale score ≥ 10) among pregnant women near delivery was 3.36% (479/14,243) [2]. It is unclear whether the baseline antenatal mental status was similar in the women allocated to the two groups, as this could impact postpartum depression.…”

A holistic approach to maternal mental health: beyond epidural analgesia

“…The StEP-COMPAC consensus recommends defining acute myocardial injury according to the criteria outlined in the Fourth Universal Definition of Myocardial Infarction, which include a troponin value above the 99th percentile upper reference limit and a change from the baseline of > 20% [4]. However, it is unclear whether pre-operative…”

“…Prenatal depression is a strong predictor of postpartum depression. A recent randomised controlled trial of a single low-dose esketamine infusion (0.2 mg.kg -1 over 40 min) after childbirth once the umbilical cord had been clamped, for mothers with prenatal depression, reduced major depressive episodes 42 days postpartum by about three-quarters when compared with placebo (12/180, 6.5% vs. 46/181, 25.4%, relative risk (95%CI) 0.26 (0.14-0.48), p < 0.0001)[4].Despite no clear signal of an effect of epidural analgesia on postpartum depression, it is associated with a 35% reduction in severe maternal morbidity, with the greatest effects seen in those with a medical indication for epidural analgesia (e.g. serious cardiovascular or respiratory disease) or delivering preterm[5].…”