There was considerable interest during the last decade in the usage of ketamine as an antidepressant. While ketamine is definitely not a primary line treatment for depression, researchers have questioned whether ketamine administered on the time of delivery may very well be used to either treat or prevent postpartum depressive symptoms. Most of those studies come from China, where ketamine is usually used for perioperative pain management after Cesarean section. The studies have yielded mixed results; nevertheless, a recent study from Yang and colleagues (2022) suggests that ketamine can have much greater effects in women at high risk for PPD, as in comparison with women at lower risk. This study used mathematical modeling to discover five variables that predicted PPD on this population: stress while pregnant, mood while pregnant, domestic violence, prenatal self-harm ideation and elevated prenatal EPDS rating.

In one other study, Li and colleagues use logistic regression and machine learning algorithms to predict the effectiveness of IV ketamine or esketamine administered during cesarean section for the prevention of PPD. The researchers analyzed data from two randomized controlled trials, and focused on 12 prenatal features in 507 women who received intravenous ketamine or esketamine on the time of cesarean section.

Several different prediction models were tested using prenatal features and ketamine dosage regimen as predictors. They observed the next:

• Women with prenatal EPDS scores of 10 or greater or thoughts of self-injury were less prone to profit from ketamine
• The next dose of esketamine (0.25 mg/kg loading dose + 2 mg/kg PCIA) was probably the most effective dosage regimen
• On the whole, esketamine was simpler and had fewer uncomfortable side effects than ketamine 

What we are able to glean from these studies is that while IV ketamine or esketamine will not be an acceptable intervention for all women, some women may profit. The studies from Yang and colleagues indicate that ladies at high risk for PPD based on certain risk aspects (higher prenatal EPDS scores, prenatal thoughts of self-injury, domestic violence, and stress while pregnant) usually tend to experience a discount in risk for PPD than women at low risk.

The research of Li and colleagues builds on these earlier findings, noting that ladies with higher prenatal EPDS scores and self-harm ideation are less prone to profit from ketamine.  They recommend that ladies with these risk aspects may respond higher to the next dose of esketamine. On the whole, they note that esketamine is simpler and higher tolerated than ketamine.

While there could also be comprehensible resistance to using ketamine, one could imagine that this could be a sexy intervention for ladies at high risk for PPD, for instance women with a history of severe PPD after a previous pregnancy. Intravenous ketamine could easily be administered on the time of delivery; nevertheless, further studies are mandatory to raised understand who’s most probably to profit from this intervention.  

Ruta Nonacs, MD PhD

References

Li Q, Gao K, Yang S, Yang S, Xu S, Feng Y, Bai Z, Ping A, Luo S, Li L, Wang L, Shi G, Duan K, Wang S. Predicting efficacy of sub-anesthetic ketamine/esketamine i.v. dose during course of cesarean section for PPD prevention, utilizing traditional logistic regression and machine learning models. J Affect Disord. 2023 Jul 13; 339:264-270.

Yang ST, Yang SQ, Duan KM, Tang YZ, Ping AQ, Bai ZH, Gao K, Shen Y, Chen MH, Yu RL, Wang SY. The event and application of a prediction model for postpartum depression: optimizing risk assessment and prevention within the clinic. J Affect Disord. 2022 Jan 1;  296:434-442.