# Ketamine to reduce postpartum depression and pain after cesarean delivery

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $542,296

## Abstract

PROJECT SUMMARY (ABSTRACT)
Postpartum depression (PPD) affects 28 million mothers worldwide in the first year after birth, risking suicide—
a leading cause of maternal death globally—and placing children at risk for future mental health problems.
Cesarean delivery (CD) is the most common major abdominal surgery in the world, and a lack of data on new
pain treatments in pregnancy and lactation puts 1.2 million US women every year after CD at risk for poor pain
control, depressed mood, and poor recovery. Despite high individual variability in pain after CD, current CD
treatments ignore the multidimensionality of pain. NMDA receptor antagonists like ketamine are known to
reduce postoperative pain and opioid use in non-obstetric surgical populations, and recently, ketamine has
been recognized for its utility in treating depression. Although limited-use postpartum ketamine studies show
no evidence of serious negative effects, ketamine has known and undesirable side effects (e.g., nausea,
dysphoria) which can interfere with newborn care. Studies on pregnant/lactating women are limited by lack of
data on optimal dose and long-term PPD and pain recovery outcomes. This knowledge gap precludes
understanding how ketamine might reduce PPD and pain in this population. There is a critical need for better
treatments to reduce PPD risk and pain after CD. To address these needs, we will identify ketamine’s tolerable
dose, pharmacokinetics, and pharmacodynamics after CD so that future randomized trials using appropriately
dosed ketamine in postpartum women can be conducted. Our long-term goal is to reduce the burden and
impact of depression and pain in special populations. Our central hypothesis is that post-CD ketamine reduces
PPD risk by reducing pain in multiple dimensions. Specific Aims: A1: Quantify tolerable dose of postpartum
ketamine using MTD design. A2: Identify PK/PD of postpartum ketamine infusion in an open-label
observational study. A3: Identify change points/trajectories of PPD symptoms to inform future postpartum
ketamine trial outcomes. This proposal has the potential to change practice because preventive therapies for
PPD are lacking, and the dearth of alternative non-opioid analgesia after CD has been a critical barrier to
progress in postpartum pain recovery. Our approach is innovative because it employs novel theoretical
concepts to postpartum multimodal pain management strategies. It addresses gaps in prior studies that used
best-guess doses of ketamine, leading to variable results on efficacy and side effects. This work will identify
new therapeutic strategies that reduce both PPD risk and postpartum pain. It will directly inform the next steps
for a randomized trial on post-CD ketamine at a tolerable dose, for PPD and pain recovery outcomes.

## Key facts

- **NIH application ID:** 10872230
- **Project number:** 5R01MH134538-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Grace Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $542,296
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872230

## Citation

> US National Institutes of Health, RePORTER application 10872230, Ketamine to reduce postpartum depression and pain after cesarean delivery (5R01MH134538-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10872230. Licensed CC0.

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