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Esketamine After C-Section Eased Postpartum Depression Symptoms

— Symptoms were reduced a week after delivery, but effects faded rapidly

MedpageToday
 A photo of a mom slumped on her couch as her baby plays on the floor.

Intravenous esketamine given during and after C-section diminished postpartum depression (PPD) symptoms early after birth, a randomized controlled trial in China showed.

Women who received IV esketamine had a significantly lower prevalence of PPD symptoms 7 days after birth compared with those who didn't get the drug (23% vs 35.3%; OR 0.55, 95% CI 0.33-0.91, P=0.02), according to Xiao-Dan Wu, MD, of Fujian Medical University in China, and colleagues.

However, there were no differences in PPD symptoms between groups at days 14, 28, or 42 after birth, they reported in .

"An intravenous injection of esketamine during the perioperative period of elective cesarean delivery was effective in improving depressive symptoms in the early postpartum period, although the effect faded rapidly over time," the researchers concluded.

Esketamine and its sister compound ketamine are glutamatergic N-methyl-D-aspartate (NDMA) receptor antagonists. Studies have shown that NMDA receptor abnormalities may play a role in various psychiatric disorders, including depression disorders, by affecting glutamatergic neurotransmission, the researchers said. Thus, there's been more attention around preventing PPD by using NMDA receptor antagonists.

In the U.S., ketamine is approved as an anesthetic, but not for mood disorders. Esketamine (Spravato) is approved in the U.S. as a nasal spray for treatment-resistant depression and major depressive disorder with acute suicidal ideation or behavior.

This double-blind, placebo-controlled trial, conducted at a single center in China throughout 2022, enrolled 298 pregnant women ages 18 to 40 years undergoing elective C-section and randomly assigned to IV esketamine (n=148) or control (n=150). Median age was 31 years in both groups.

Those in the esketamine group received two doses of the drug: one IV dose of 0.25 mg/kg immediately after delivery, and another 50-mg dose in patient-controlled IV analgesia for 48 hours after surgery. Controls received saline.

PPD symptoms were assessed using the , and a positive screen was defined as a score of 10 or more points. The primary outcome was PPD symptoms at postpartum day 7.

Wu and colleagues found that patients in the esketamine group had a significantly lower change in EPDS scores (effect size 0.74, P=0.008), but there were no differences between groups in the incidence of positive screening results for PPD.

There were also no differences in postoperative pain scores on a numeric rating scale of 0 to 10 points, the researchers reported.

The medication was generally well tolerated, with no difference in the incidence of nausea and vomiting between groups. Also, mothers in the esketamine group didn't show any significant differences in mental symptoms, including dizziness, headaches, somnolence, hallucinations, nightmares, and nystagmus, compared with controls.

The study was limited because it couldn't assess potential confounding factors, such as socioeconomic status, spousal and family support, and other stressful life events. Postpartum day 42 is typically the peak period for PPD to manifest, which was the final follow-up point in the study. The findings also might lack generalizability outside mothers in China.

  • author['full_name']

    Michael DePeau-Wilson is a reporter on MedPage Today’s enterprise & investigative team. He covers psychiatry, long covid, and infectious diseases, among other relevant U.S. clinical news.

Disclosures

The trial was funded by grants from the National Natural Science Foundation of China, the Fujian Provincial Health Technology Project, the Natural Science Foundation of Fujian Province, and the Startup Fund for Scientific Research, Fujian Medical University.

The authors reported no financial conflicts of interest.

Primary Source

JAMA Network Open

Chen Y, et al "Perioperative adjunctive esketamine for postpartum depression amongwomen undergoing elective cesarean delivery: A randomized clinical trial" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.0953.