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) 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.