Accredited 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 just lately, we have now realized that ketamine and esketamine administered at sub-anestetic doses have speedy antidepressant and anti-suicidal results.
A number of research have explored using ketamine and ketamine for the remedy of PPD. Most of those research haven’t examined ketamine or esketamine as an antidepressant particularly for the remedy of ladies 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 research 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 Melancholy Scale (EPDS) rating of 10 or better on the time of supply, however no historical past of despair previous to being pregnant, had been randomly assigned to obtain both 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth. Assessments had been carried out 18-30 hours after childbirth, at 1 week postpartum, and once more at 6 weeks.
The outcomes had been pretty exceptional. EPDS scores had 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 members 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 unwanted 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 nervousness, misery, or terror just like nightmares (3.3% vs. 0%). About 10% of members within the esketamine group required momentary interruption of the infusion on account of dizziness. Unwanted side effects had been transient and didn’t require any medical intervention.
In abstract, this research demonstrated {that a} single dose of esketamine administered intravenously to girls with delicate depressive signs at supply was related to lowered depressive signs at week 1 postpartum. As well as, those that obtained esketamine had a 75% decrease threat of experiencing important depressive signs at 6 weeks postpartum.
Who’s a Good Candidate for Ketamine?
Up to now, most research exploring using ketamine and esketamine for postpartum despair haven’t been conventional remedy research, the place a specific medicine or placebo is run to girls with postpartum despair. As an alternative, ketamine or esketamine is run to girls present process cesarean part, and depressive signs are assessed in the course of the postpartum interval.
A current 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 lowered 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 remedy of PPD.
Whereas the outcomes of the BMJ research are spectacular, it included a really well-defined subgroup of ladies, 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 by way of postpartum ache aid, 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 remedy of postpartum despair and, if helpful on this setting, which girls are most certainly to profit from this remedy.
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 software 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.
