Esketamine during elective cesarean delivery may reduce postpartum depression
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Key takeaways:
- At 7 days postpartum, esketamine was associated with significantly lower depressive symptom prevalence vs. placebo.
- No differences in depression incidence were noted between groups at 14, 28 and 42 days.
Esketamine administered intravenously during elective cesarean delivery may significantly reduce depressive symptoms in the early postpartum period, according to study results published in JAMA Network Open.
“Recently, esketamine, a novel antagonist of the N-methyl-D-aspartate receptor with a higher affinity than ketamine, has been used in several countries, including China,” Yu Chen, MD, from the department of anesthesiology at Shengli Clinical Medical College of Fujian Medical University, China, and colleagues wrote. “As a dextral resolution of ketamine, esketamine has been shown to improve the effectiveness of anesthetics and analgesics, with a similar antidepressant effect to its predecessor.”
Chen and colleagues conducted a single-center, double-blind, placebo-controlled, prospective, randomized clinical trial in 2022 with data from 298 pregnant women (median age, 31 years) who were scheduled for elective cesarean deliveries of a singleton pregnancy at full term at Fujian Provincial Hospital. All women had an American Society of Anesthesiologists (ASA) grade I to III classification, with grade I denoting healthy patients and grade III denoting those with severe, nonthreatening systemic disease.
Women were randomly assigned to esketamine 0.25 mg/kg IV immediately after delivery followed by adjuvant esketamine 50 mg in patient-controlled IV analgesia for 48 hours after surgery (n = 148) or IV saline (n = 150).
Primary outcome was postpartum depression symptoms assessed by the Edinburgh Postnatal Depression Scale (EPDS) at 7 days postpartum, with a score of 10 or more indicating a positive postpartum depression screen. Secondary outcomes included postoperative pain assessed by the numeric rating scale (NRS) and esketamine safety at 14, 28 and 42 days postpartum.
At 7 days postpartum, the esketamine group had lower depressive symptom prevalence compared with the control group (23% vs. 35.3%; OR = 0.55; 95% CI, 0.33-0.91; P = .02). The esketamine group also had lower EPDS score changes compared with the control group at 7 days postpartum (least-squares mean difference = –1.17; 95% CI, –2.04 to –0.31; P = .008).
Researchers observed no differences in positive postpartum depression screening incidence or changes from baseline EPDS scores at 14, 28 and 42 days postpartum between the esketamine and control groups. In addition, researchers noted no differences in postoperative pain scores at rest and during movement, except for movement at 72 hours after surgery, wherein the esketamine group had lower scores compared with the control group (P = .03).
Esketamine was generally well tolerated with no difference in nausea and vomiting incidence between the two groups. The esketamine group also had no significant differences in mental symptoms, such as dizziness, headaches, somnolence, hallucinations, nightmares and nystagmus, compared with the control group.
The researchers noted some limitations, one of which was that all participants were new Chinese mothers, so the findings may lack generalizability. According to the researchers, multicenter studies that involve different regions, countries, races and ethnicities are needed to confirm or negate the findings.
“Overall, our study demonstrated a potential beneficial effect of perioperative adjunctive esketamine administration on the treatment of postpartum depression in women undergoing elective cesarean deliveries,” the researchers wrote.
Editor’s note: This article was updated on March 12 to include a study limitation.
Perspective
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Mental health disorders, including postpartum depression, are the leading cause of preventable maternal mortality in the U.S. Thus, it is incredibly important to investigate many different strategies in preventing such complications. The authors of this study investigated the use of the drug esketamine, in addition to routine medications given at the time of cesarean, to assess its effect of postpartum depression. While the authors found lower rates of depression symptoms at 1 week postpartum in the group of patients who received esketamine, they did not find lower rates of postpartum depression at that time point or at any time point up to 6 weeks postpartum. As postpartum depression can occur any time in the first year postpartum, longer follow-up is needed for studies that aim to decrease the rates of postpartum depression.
Esketamine has been studied for pain control at the time of cesarean in previous studies as well. However, higher rates of postoperative vomiting (up to 17%) and neurologic symptoms including vertigo (45%) and hallucination (up to 7%) were noted compared with patients who did not receive esketamine. Cesarean birth differs from other surgical procedures in that patients strongly desire to remember the experience as it is the time when they meet their newborn. Therefore, extreme care should be taken in adopting the use of a drug that can not only change the way a patient experiences the procedure, but also their memories following the procedure.
The benefits of esketamine on maternal mental health disorders require further study before we would recommend implementing this as part of our patient care. As ketamine and esketamine have been studied for the use in treatment refractory depression, there may yet be a role for it in the treatment of perinatal mental health disorders including postpartum depression, but more research is needed.
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