Esketamine bolus reduces PPD incidence at 6 weeks to 9.15% compared to 19.33% in salineTrial shows Esketamine bolus reduces postpartum depression risk

Drug design, development and therapy Published June 29, 2026 Study authors: Yang Jie, Yan Qiqi, Zhang Ting, Hu Yaoyue, Peng Fangliang, Zhao Ruihan, Deng Meiling, Ren Li PubMed ↗ DOI ↗ Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain

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Key Takeaway

Note that esketamine bolus reduces 6-week PPD incidence and shows fewer intraoperative adverse events than infusion.

This randomized controlled trial enrolled 503 subjects without prenatal depression undergoing caesarean delivery to evaluate the efficacy of esketamine in preventing postpartum depression (PPD). Participants were assigned to receive either an esketamine bolus (0.25 mg/kg), an esketamine continuous infusion (0.25 mg/kg), or a normal saline control.

At 6 weeks postpartum, the incidence of PPD (EPDS score > 10) was 9.15% in the bolus group compared to 19.33% in the saline group (RR 0.47; 95% CI 0.25-0.91). No statistically significant difference was found between the bolus and infusion groups at 6 weeks (9.15% vs 11.54%; RR 0.79; 95% CI 0.40-1.57). No significant differences were observed for PPD incidence at 1 or 4 weeks postpartum, nor were there differences in analgesic effects among the three groups.

Regarding safety, the bolus group experienced fewer intraoperative adverse events (45.75% vs 65.38%) and less dizziness and nausea/vomiting during surgery compared to the infusion group. While both esketamine administration methods are comparable for preventing PPD, the bolus route may be preferred due to a lower incidence of certain adverse events.

How this fits prior evidence

How this fits prior evidence: This finding extends previous evidence that esketamine significantly reduces postoperative anxiety and depressive symptoms in adult patients. It also builds upon findings that esketamine improves response in treatment-resistant depression, though it specifically addresses the prevention of postpartum depression (PPD) in a surgical population. While earlier data noted dose-dependent adverse events with esketamine, this study suggests bolus administration may offer a more tolerable profile than continuous infusion for PPD prevention.

Researchers conducted a randomized controlled trial to see if esketamine could help prevent postpartum depression. The study included 503 women who did not have depression before giving birth and underwent a cesarean delivery. They compared two ways of giving esketamine: a bolus (a single dose) and a continuous infusion, against a saline solution.

The results showed that the group receiving the esketamine bolus had a lower rate of postpartum depression at six weeks compared to the saline group. However, there was no significant difference in depression rates between those who received the bolus and those who received the continuous infusion. Pain levels were similar across all three groups.

Safety data showed that the bolus method resulted in fewer instances of dizziness, nausea, and vomiting during surgery compared to the infusion method. While both ways of giving esketamine were effective at preventing depression, the bolus might be easier for patients to tolerate during the procedure. You should talk with your doctor about these options if you are concerned about postpartum depression.

What this means for you:

Esketamine bolus may reduce postpartum depression risk and have fewer side effects than continuous infusion.

Common questions

Is it safe to use esketamine for postpartum depression?

The study included 503 women and found that both bolus and infusion methods were effective at reducing the incidence of postpartum depression. While both methods worked, the bolus method resulted in fewer cases of dizziness, nausea, and vomiting during surgery compared to the continuous infusion.

What is the difference between a bolus and an infusion?

In this study, both the bolus and the continuous infusion were comparable in preventing postpartum depression at six weeks. However, the bolus administration showed a lower incidence of certain adverse events like nausea and vomiting during surgery compared to the infusion method.

How does esketamine compare to other treatments for pain?

The study measured pain scores across three groups: those receiving an esketamine bolus, an esketamine infusion, and a saline solution. The results showed that analgesic effects were comparable across all three groups.

Study Details

Study typeRct

EvidenceLevel 2

PublishedJan 2026

PMID42369371

View Original Abstract ↓

BACKGROUND: Esketamine is increasingly being applied for preventing postpartum depression (PPD). However, clinical protocols for this application are inconsistent, particularly concerning the route of administration. The aim was to determine whether esketamine bolus administration differed from continuous infusion in terms of preventing PPD. METHODS: A total of 503 subjects without prenatal depression undergoing caesarean delivery were included in this superiority trial and randomly allocated to three groups: the esketamine bolus group received a bolus injection of 0.25 mg/kg esketamine, the esketamine infusion group was administered a continuous infusion of 0.25 mg/kg esketamine, while the control group was given an equivalent volume of normal saline. Primary outcome was set as the incidence of PPD at 6 weeks postpartum. The positive screening of PPD was defined as Edinburgh Postnatal Depression Scale (EPDS) with scores of more than 10. Incidence of PPD at 1 and 4 weeks postpartum, pain scores and all adverse events were also assessed. RESULTS: Esketamine bolus administration significantly reduced the incidence of PPD compared with control group (9.15% vs 19.33%; RR 0.47, 95% CI 0.25-0.91). However, no statistically significant difference was observed between the bolus group and the infusion group (9.15% vs 11.54%; RR 0.79, 95% CI 0.40-1.57). There were no significant differences in PPD incidence at 1 and 4 weeks postpartum among the three groups. Similarly, the analgesic effects were comparable across the three groups. Regarding adverse events, less dizziness and nausea/vomiting during surgery was revealed with esketamine bolus administration. Overall, subjects receiving esketamine bolus administration also experienced fewer intraoperative adverse events than those in the infusion group (45.75% vs 65.38%, RR 0.73, 95% CI 0.56-0.95). CONCLUSION: For patients without prenatal depression undergoing caesarean delivery, esketamine bolus administration or continuous infusion demonstrated comparable efficacy for preventing PPD, bolus administration may be the preferred route due to a lower incidence of adverse events.

Esketamine bolus reduces PPD incidence at 6 weeks to 9.15% compared to 19.33% in salineTrial shows Esketamine bolus reduces postpartum depression risk

How this fits prior evidence

Common questions

Study Details

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Esketamine bolus reduces PPD incidence at 6 weeks to 9.15% compared to 19.33% in salineTrial shows Esketamine bolus reduces postpartum depression risk

How this fits prior evidence

Common questions

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Study Details

PETRUSHKA decision-support tool reduced treatment discontinuation and improved symptoms in major depressive disorder

The Algorithm That Helps Doctors Pick the Right Antidepressant for You

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