Q&A: Peter Hsin, BS, on perioperative ketamine and early postpartum depression

Giving ketamine or esketamine during elective cesarean delivery was associated with lower early postpartum depressive symptom scores, according to a meta-analysis presented as a poster at the American Society of Anesthesiologists’ ANESTHESIOLOGY 2026 annual meeting, held October 16-20, 2026, in San Diego, California.¹

According to the study authors, postpartum depression affects approximately 20% of women after childbirth and carries significant consequences for both mother and infant. Cesarean delivery has been tied to a higher risk of depressive symptoms after birth, which has drawn attention to perioperative strategies that might ease early mood disturbances. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist widely used for anesthesia and analgesia, has produced rapid antidepressant effects in psychiatric populations.

What did the ketamine meta-analysis find?

The investigators searched PubMed, ScienceDirect, and APA PsycINFO for randomized controlled trials published from January 2015 to September 2025 in adults undergoing elective cesarean section. Eligible trials compared ketamine or esketamine, given before, during, or after surgery, with placebo or standard anesthetic care, and reported Edinburgh Postnatal Depression Scale (EPDS) scores between postoperative days (POD) 3 and 14. Results were pooled with a random-effects, inverse-variance model.

Across 6 randomized controlled trials, perioperative ketamine or esketamine was associated with a significant reduction in early postpartum depressive symptoms compared with control (SMD = −0.36; 95% CI −0.49 to −0.22). Heterogeneity was moderate (I² = 47.5%), with low between-study variance (τ² = 0.013), and most trials showed lower EPDS scores with ketamine despite differences in dosing, timing, and anesthetic protocols.

The authors described the reduction as modest but statistically significant, suggesting ketamine may offer psychiatric benefit beyond analgesia in the peripartum surgical setting. They called for further randomized trials with standardized dosing and longer follow-up to determine whether perioperative ketamine can lower the incidence of clinically diagnosed postpartum depression.

In a written interview with Contemporary OB/GYN, lead author and medical student Peter Hsin, BS, of FIU Herbert Wertheim College of Medicine in Miami, Florida, discussed how to interpret the size of the effect, what the variability in dosing and timing means for practice, and how ob-gyns can approach the evidence with anesthesia colleagues.²

Q&A with Peter Hsin, BS

Contemporary OB/GYN: Can you summarize what this meta-analysis found on perioperative ketamine and early postpartum depressive symptoms, and what prompted you to examine this question in the cesarean setting?

Hsin: Our meta-analysis included 6 randomized controlled trials examining whether perioperative ketamine or esketamine could reduce early postpartum depressive symptoms following elective cesarean delivery. We found that patients who received ketamine had significantly lower depressive symptom scores compared with those in the control groups, with a pooled standardized mean difference of -0.36. While the effect was modest, the overall findings suggest that ketamine may have benefits extending beyond its established role in perioperative pain management.

What interested us about this question was the growing recognition of postpartum depression as a major maternal health concern, particularly following cesarean delivery. Ketamine has demonstrated rapid antidepressant effects in other clinical settings, so we wanted to investigate whether administering it around the time of surgery could provide similar benefits during the early postpartum period.

Contemporary OB/GYN: The pooled effect was an SMD of −0.36, which you describe as modest but statistically significant. How should ob-gyns interpret that magnitude, and does a reduction in EPDS scores between POD 3 and 14 translate into a clinically meaningful difference for patients?

Hsin: An SMD of -0.36 represents a small-to-moderate improvement in depressive symptom scores among patients receiving ketamine compared with controls. Although this may not seem like a dramatic effect, even modest improvements in mood during the early postpartum period could be valuable, especially when patients are recovering from major surgery while adjusting to caring for a newborn.

However, it’s important to distinguish statistical significance from clinical significance. The Edinburgh Postnatal Depression Scale (EPDS) is a screening tool, and previous research has identified a 4-point change as a threshold for reliably detecting improvement in an individual’s symptoms. Our analysis used standardized differences between treatment groups rather than individual changes in EPDS scores, so we cannot conclude that this threshold was achieved.

I think the results are encouraging, but we still need studies examining whether these early improvements translate into meaningful outcomes for patients, such as reduced rates of clinically diagnosed postpartum depression, improved daily functioning, or better long-term mental health.

Contemporary OB/GYN: The included trials varied in ketamine and esketamine dosing, timing (preoperative, intraoperative, or postoperative), and anesthetic protocols. What can clinicians conclude about optimal dosing or timing, and what would a standardized protocol need to address?

Hsin: One of the main challenges we identified was the variability in how ketamine was administered across the included studies. Despite differences in dosing, timing, and anesthetic techniques, the overall findings favored ketamine. However, we cannot determine whether one specific dose or administration window is more effective than another.

Before establishing a standardized protocol, future studies would need to directly compare different dosing strategies and administration times. It’s also important to distinguish between ketamine and esketamine, as well as account for differences in anesthetic and postoperative pain management protocols.

Ideally, a standardized approach would identify a dose and timing strategy that provides consistent antidepressant benefits while minimizing adverse effects. It would also need to establish appropriate patient selection criteria, maternal monitoring requirements, and safety considerations for the newborn. At this point, our findings support further investigation rather than recommending a specific protocol for routine clinical practice.

Contemporary OB/GYN: The analysis measured symptom severity on the EPDS, not clinically diagnosed postpartum depression, and was limited to elective cesarean delivery with short follow-up. What are the key limitations ob-gyns should keep in mind before applying these findings to practice?

Hsin: The biggest limitation is that our study evaluated early depressive symptoms rather than clinically diagnosed postpartum depression. While lower EPDS scores are encouraging, they do not necessarily mean that ketamine prevents patients from developing postpartum depression later on.

Another important consideration is the relatively short follow-up period. We examined EPDS scores collected between postoperative days 3 and 14, so we cannot determine whether the observed benefits persist for several weeks or months after delivery.

Additionally, all included studies involved elective cesarean deliveries, which limits how confidently we can generalize these findings to emergency cesarean procedures or vaginal deliveries. There were also differences in dosing and anesthetic protocols across studies, and the analysis included only six randomized trials.

For ob-gyns, I think the key takeaway is that ketamine shows promise for reducing early postpartum depressive symptoms, but the evidence is not yet sufficient to recommend it specifically for postpartum depression prevention in routine practice.

Contemporary OB/GYN: For an ob-gyn who doesn’t control anesthetic choices, how should this evidence factor into conversations with anesthesia colleagues, and what safety considerations or patient selection questions should be part of that discussion?

Hsin: I think these findings create an opportunity for closer collaboration between ob-gyns and anesthesiologists. While anesthetic decisions are generally made by the anesthesia team, ob-gyns play an important role in identifying patients who may be at increased risk for postpartum depression and discussing their concerns before delivery.

For patients undergoing cesarean delivery, it may be worthwhile to discuss whether ketamine is already being considered as part of their perioperative pain management plan and what potential benefits or risks might be relevant.

Patient selection is particularly important. Ketamine can produce adverse effects such as dizziness, dissociation, hallucinations, and increases in blood pressure or heart rate. Clinicians should consider cardiovascular conditions, psychiatric history, and other individual risk factors. Breastfeeding plans and neonatal safety should also be part of the discussion, as the available evidence remains limited.

I would emphasize that our study does not support administering ketamine solely to prevent postpartum depression at this time. Rather, it provides additional information that OB-GYNs and anesthesiologists can consider together when developing individualized perioperative care plans.

Contemporary OB/GYN: Postpartum depression affects roughly 20% of women, and cesarean delivery is linked to higher risk. What does it mean that a single perioperative intervention may offer psychiatric benefit on top of analgesia, and how might that change how we think about the surgical setting as a window for prevention?

Hsin: I think this is one of the most interesting implications of our findings. We traditionally think about perioperative medications in terms of their immediate effects on pain control, anesthesia, and recovery. However, ketamine raises the possibility that an intervention administered during surgery could also influence a patient’s mental health during the days that follow.

The early postpartum period can be especially challenging, as patients are simultaneously recovering physically and adjusting to significant emotional and lifestyle changes. If an intervention already being considered in the perioperative setting could also help reduce depressive symptoms, that would be a meaningful opportunity to improve overall maternal care.

More broadly, I think this research encourages us to view the surgical setting as an opportunity to support both physical and psychological recovery. We are not yet at the point of calling ketamine a proven preventive treatment for postpartum depression, but the possibility of addressing multiple aspects of recovery through a single intervention is certainly worth investigating further.

Contemporary OB/GYN: Despite differences in dosing, timing, and anesthetic protocols, most of the included trials favored ketamine, with only moderate heterogeneity. How encouraging is that consistency, and what would the next generation of trials need to show to move this toward routine practice?

Hsin: I find the consistency across studies encouraging. All 6 trials showed an effect in the direction of lower depressive symptom scores with ketamine, although not every individual study reached statistical significance. Considering the differences in dosing, timing, and anesthetic protocols, seeing a similar direction of effect suggests that the potential benefit is worth studying further.

At the same time, moderate heterogeneity indicates that the size of the benefit varied across studies, so we still have questions about which patients might benefit most and what administration strategy would be most effective.

The next step would be larger, multicenter randomized controlled trials using standardized protocols and longer follow-up periods. These studies should assess not only EPDS scores but also rates of clinically diagnosed postpartum depression, maternal functioning, breastfeeding outcomes, and adverse effects.

Ultimately, I think the strongest evidence would come from demonstrating that a specific perioperative ketamine regimen can safely produce meaningful and sustained improvements in maternal mental health. That would be an important step toward determining whether ketamine should become a routine component of postpartum depression prevention strategies.

Reference:

1. Hsin P, Siu S, Simon S, et al. Perioperative ketamine effect on early postpartum depression symptoms after cesarean section: a meta-analysis. Poster presented at: ANESTHESIOLOGY 2026, American Society of Anesthesiologists Annual Meeting; October 16-20, 2026; San Diego, California.
2. Ketamine during or after C-sections may ease early postpartum depression symptoms, new study suggests. American Society of Anesthesiologists. News release. Published October 17, 2026. Accessed November 3, 2026. https://www.asahq.org/about-asa/newsroom/news-releases/2026/10/ketamine-during-or-after-c-sections-may-ease-early-postpartum-depression-symptoms