Accepted by the FDA as an anesthetic in 1970, ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used for many years. Extra not too long ago, we’ve got realized that ketamine and esketamine administered at sub-anestetic doses have speedy antidepressant and anti-suicidal results.
A number of research have explored the usage of ketamine and ketamine for the therapy of PPD. Most of those research haven’t examined ketamine or esketamine as an antidepressant particularly for the therapy of girls with postpartum despair; as a substitute these research have measured depressive signs in girls receiving ketamine or esketamine as an anesthetic agent administered throughout or after a Cesarean part.
In a extremely publicized examine revealed within the BMJ final month, researchers investigated the efficacy of a single low dose of esketamine administered after childbirth to moms with depressive signs throughout being pregnant. On this randomized managed trial, 364 girls with an Edinburgh Postnatal Despair Scale (EPDS) rating of 10 or larger on the time of supply, however no historical past of despair previous to being pregnant, have been randomly assigned to obtain both 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth. Assessments have been carried out 18-30 hours after childbirth, at 1 week postpartum, and once more at 6 weeks.
The outcomes have been pretty exceptional. EPDS scores have been decrease within the esketamine group at 1 week (median distinction ?3) and at 6 weeks (median distinction ?3). At 6 weeks postpartum, PPD was noticed in 6.7% of contributors within the esketamine group in comparison with 25.4% of these within the placebo group (relative threat 0.26, 95% confidence interval (CI) 0.14 to 0.48; P < 0.001).
Not surprisingly, girls within the esketamine group reported extra uncomfortable side effects than these receiving placebo (45.1% vs. 22.0%), together with sedation (5.5% vs. 0.5%), dizziness (26.4% vs. 9.3%), double imaginative and prescient (4.9% vs. 0%), and hallucinations or acute anxiousness, misery, or terror just like nightmares (3.3% vs. 0%). About 10% of contributors within the esketamine group required short-term interruption of the infusion attributable to dizziness. Unwanted effects have been transient and didn’t require any medical intervention.
In abstract, this examine demonstrated {that a} single dose of esketamine administered intravenously to girls with delicate depressive signs at supply was related to diminished depressive signs at week 1 postpartum. As well as, those that obtained esketamine had a 75% decrease threat of experiencing vital depressive signs at 6 weeks postpartum.
Who’s a Good Candidate for Ketamine?
So far, most research exploring the usage of ketamine and esketamine for postpartum despair haven’t been conventional therapy research, the place a specific remedy or placebo is run to girls with postpartum despair. As a substitute, ketamine or esketamine is run to girls present process cesarean part, and depressive signs are assessed throughout the postpartum interval.
A latest meta-analysis (Wen et al, 2024) analyzed seven research and a complete of 669 sufferers handled with esketamine and 619 comparisons. Whereas esketamine was not used to deal with depressive signs, the meta-analysis demonstrated that girls receiving esketamine had decrease ranges of postpartum depressive signs, and the general incidence of PPD was diminished in these receiving esketamine after a cesarean part. Even at 42 days postpartum, the incidence of PPD was nonetheless considerably decrease within the esketamine group. Comparable outcomes have been noticed in people receiving ketamine after Cesarean part (Li et al, 2024). So primarily based on these findings, it seems that ketamine and esketamine could stop or scale back threat for PPD, however these research don’t inform us whether or not esketamine and ketamine can be efficient for the therapy of PPD.
Whereas the outcomes of the BMJ examine are spectacular, it included a really well-defined subgroup of girls, particularly girls with no historical past of despair previous to being pregnant who developed delicate depressive signs throughout being pregnant (with a median EPDS rating of 10). In scientific follow, girls with delicate depressive signs and no historical past of despair previous to being pregnant can be referred for psychotherapy and monitoring. Though there are advantages to esketamine when it comes to postpartum ache reduction, would girls with delicate signs elect to obtain an intravenous infusion of esketamine on the time of supply?
Additional research are wanted to find out whether or not ketamine and esketamine are efficient for the therapy of postpartum despair and, if helpful on this setting, which girls are almost certainly to profit from this therapy.
Ruta Nonacs, MD PhD
References
Wang S, et al. Efficacy of a single low dose of esketamine after childbirth for moms with signs of prenatal despair: randomised scientific trial. BMJ 2024; 385:e078218.
Wen Y, Mao M, Wang X, Xu C, Shi X, Li P, Tian Z, Jiang M, Yuan H, Feng S. Efficacy and security of perioperative utility of esketamine on postpartum despair: A meta-analysis of randomized managed research. Psychiatry Res. 2024 Mar; 333:115765.
Li S, Zhou W, Li P, Lin R. Results of ketamine and esketamine on stopping postpartum despair after cesarean supply: A meta-analysis. J Have an effect on Disord. 2024 Apr 15;351:720-728.
