Single Dose of Esketamine After Childbirth Reduces Postpartum Depression

A single esketamine injection following childbirth reduces postpartum depression in mothers with prenatal depression, a new study reported.^1,2

Previous research saw low-dose ketamine or esketamine reduces depression in mothers having a cesarean delivery but excluded mothers with prenatal depression.

“Our trial extends existing understanding by targeting women with pre-existing prenatal depression, who were therefore at high risk of postnatal depression,” wrote investigators, led by Shuo Wang, MD, from the department of anesthesiology at Peking University First Hospital in Beijing, China.

Investigators aimed to determine whether a low dose of esketamine given after childbirth reduced postpartum depression in mothers with prenatal depression. They conducted a randomized, double-blind, placebo-controlled trial with 2 parallel arms at 5 tertiary care hospitals in China from June 19, 2020, to August 3, 2022.

The sample included 364 mothers aged ≥ 18 years (mean age: 31.8 years) who had at least mild prenatal depression, determined by an Edinburgh postnatal depression scale score of ≥ 10 (range 0 – 30), and delivered their child in a hospital. They were excluded if they had a pre-pregnancy history of mood disorders, including depression. Participants were randomized 1:1 to either receive a 40-minute injection of 0.2 mg/kg esketamine or a placebo following childbirth after the umbilical cord had been clamped.

The primary outcome was the prevalence of a major depressive episode at 42 days postpartum, diagnosed with a mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at 7 and 42 days postpartum and the 17-item Hamilton depression rating score at 42 days postpartum. The team monitored adverse events until 24 hours after childbirth.

At 42 days postpartum, Wang and colleagues observed fewer major depressive episodes for participants who had an esketamine injection following childbirth compared to a placebo injection (6.7% vs 25.4, respectively; relative risk [RR], 0.26; 95% confidence interval [CI], 0.14 to 0.48; P < .001).

Compared to placebo, participants who received esketamine had lower postnatal depression scale scores at 7 days (mean difference, -3; 95% CI, - 4 to -2; P < .001) and 42 days (- 3; 95% CI, -4 to -2; P < .001). As for the Hamilton depression rating scale at 42 days postpartum, the esketamine group had lower scores (-4; 95% CI, -6 to -3; P < .001).

Regarding the safety profile of esketamine for postpartum depression, participants with esketamine and placebo had similar rates of blood pressure, heart rate, and oxygen saturation after 1 hour of the infusion. Participants in the esketamine group were more often sedated (4.4 vs 0.5%; P = .006), reported fewer stomach aches (1.1% vs 5.5%; P = .02), and had more neuropsychiatric symptoms (33.5% vs 11.0%; P < .001), such as more dizziness (26.4% vs. 9.3%; P < .001), diplopia (4.9% vs 0%; P = .004), and hallucinations or daymares (3.3% vs 0%; P = .03).

Although people injected with esketamine had a greater overall incidence of neuropsychic adverse events compared to placebo (45.1% vs 22.1, respectively; P < .001) the symptoms only lasted less than a day and did not require drug intervention.

“We did not find a significant correlation between neuropsychiatric symptoms and antidepressant effects of esketamine in the present study, which was in line with previously reported results,” investigators wrote.

Investigators noted the limitations of excluding mothers with pre-pregnancy mood disorders which are the ones who need intervention the most, the lack of standardized assessment tools, not evaluating the participant’s viewpoint of the drug they received, and most of the participants had only mild prenatal depression. Since the majority of participants had mild prenatal depression it is unknown if esketamine in mothers with more severe depression is just as effective.

The team concluded by stating a single low dose of esketamine after childbirth reduced major depressive episodes at 42 days postpartum by approximately 3 quarters.

^References

1. ^{Wang, S, Deng, C, Zeng, Y. Efficacy Of A Single Low Dose Of Esketamine After Childbirth For Mothers With Symptoms Of Prenatal Depression: Randomized Clinical Trial. BMJ 2024;385:e078218 | doi: 10.1136/bmj-2023-078218.}
2. ^{Esketamine Injection Just After Childbirth Reduces Depression in New Mothers. EurekAlert! April 10, 2024. https://www.eurekalert.org/news-releases/1040657?. Accessed April 10, 2024.}