There has been considerable interest over the last decade in the use of ketamine as an antidepressant. While ketamine is certainly not a first line treatment for depression, researchers have questioned whether ketamine administered at the time of delivery could be used to either treat or prevent postpartum depressive symptoms. Most of these studies come from China, where ketamine is often used for perioperative pain management after Cesarean section. The results have yielded mixed results; however, a recent study from Yang and colleagues (2022) suggests that ketamine may have much greater effects in women at high-risk for PPD, as compared to women at lower risk.
IV Ketamine and Prevention of PPD
This study actually has two parts – both of them interesting. In the first part of the study, the researchers assessed whether ketamine administered at the time of delivery would reduce risk for postpartum depression. Pregnant women receiving a cesarean section were randomized to receive either standard perioperative care (n=1004) or standard care plus IV ketamine (n=305). Women in both groups received postoperative analgesia with sufentanil 100 ?g. The ketamine group additionally received 160 mg of ketamine.
A crude analysis of the results (without controlling for potential confounders) observed that in the control group, 171 out of 1004 or 17.0% of the women developed PPD. Fewer women in the ketamine group developed PPD (39 out of 305, or 12.8%).
Ketamine More Effective in Women at Higher Risk for PPD
In the second part of the study, they identified previously reported risk factors for PPD in the control group of women (who did not receive ketamine) to develop a predictive model which could be used at the time of delivery to identify women at high risk for PPD. Using mathematical modeling, they identified five variables which predicted PPD in this population, including stress during pregnancy, mood during pregnancy, domestic violence, prenatal self-harm ideation and elevated prenatal EPDS score. The final model predicted PPD with a specificity of 0.766 and a sensitivity of 0.604.
Using this model to estimate risk in the women who received ketamine, they divided the ketamine group into high and low risk subgroups and then compared the prevalence of PPD in women at low versus high risk for PPD. While the crude analysis of the data suggested that ketamine decreased risk for PPD, it turns out that ketamine reduced risk only in women at high risk for PPD. In women at low risk for PPD, ketamine did not impact risk.
Food for Thought
This study contributes to our understanding of how to prevent postpartum depression. In this study, researchers used IV ketamine to reduce risk for PPD in a general population of women undergoing C-section, a study that is unlikely to be repeated in the United States. However, there is some useful information in this study.
Predictive models can be used to identify women at high risk for PPD in the general population. In this study, mathematical modeling was used to screen women for previously reported PPD risk factors, and the strongest predictors of risk were used to generate a predictive model. Since there are cultural differences in risk factors for PPD, it would be important to do this type of modeling in different populations in order to develop the most robust culturally sensitive predictive models.
Intravenous ketamine decreases risk of PPD in high-risk women. While a crude analysis of the results suggested that ketamine reduced risk for PPD, this prophylactic effect was observed only in women at high risk for PPD. This parallels what we have seen with other prophylactic interventions, including psychotherapy and psychoeducational interventions, where the most robust effects are observed in women at high risk for PPD.
While there may be understandable resistance to using ketamine in the general population, one could imagine that this might be an attractive intervention for women at high risk for PPD, for example women with a history of severe PPD after a previous pregnancy. A single dose of IV ketamine could easily be administered at the time of delivery; however, further studies are necessary to determine how long the prophylactic effects of ketamine last.
Ruta Nonacs, MD PhD
Yang ST, Yang SQ, Duan KM, Tang YZ, Ping AQ, Bai ZH, Gao K, Shen Y, Chen MH, Yu RL, Wang SY. The development and application of a prediction model for postpartum depression: optimizing risk assessment and prevention in the clinic. J Affect Disord. 2022 Jan 1; 296:434-442.