Ketamine for Postpartum Depression

(PREPARE-2 Trial)

Recruiting at 1 trial location

Overseen By Amy Monroe, MPH, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Grace Lim, MD, MS

Must not be taking: Psychedelics, Antipsychotics

Disqualifiers: Schizophrenia, Psychosis, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12 hours

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop taking certain medications to participate in this trial. Specifically, you cannot use oral antihypertensive medications, intravenous magnesium, ketamine, phencyclidine, psilocybins, or any antipsychotic medications like lithium or valproate. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the drug ketamine for postpartum depression?

Research suggests that ketamine can help reduce postpartum depression symptoms, especially in women who have undergone a cesarean section. Studies have shown that ketamine, when given during surgery, can lower the chances of developing postpartum depression, particularly in women with a history of stress or depression during pregnancy. ^{1 2 3 4 5}

Is ketamine safe for treating postpartum depression?

Research suggests that ketamine can be safe for treating postpartum depression, with no significant difference in overall adverse events compared to other treatments, although vomiting may occur more frequently. ^{2 6 7 8 9}

How is the drug ketamine unique in treating postpartum depression?

Ketamine is unique for postpartum depression because it acts quickly and can be administered in different ways, such as through an intravenous infusion or subcutaneous injection, which may help prevent or reduce symptoms after childbirth, especially following a cesarean delivery. ^{1 2 3 5 6}

What is the purpose of this trial?

The purpose of this study is to identify pharmacokinetics of postpartum ketamine infusion. This study will assess ketamine kinetics and metabolism in this setting. Ketamine is expected to exert different kinetics during the physiologic state of post-pregnancy. The goal in conducting this study is to better understand the pharmacokinetics and pharmacodynamics of postpartum ketamine infusion. A secondary goal is to compare these kinetics to reproductive age matched controls and to assess sex differences in ketamine pharmacokinetics. The peripartum group of this study will receive ketamine after cesarean delivery, while the control group will consist of non-pregnant female subjects and male subjects receiving the same infusion protocol.

Research Team

Grace Lim, MD, MSc

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for women who have just given birth by cesarean section and are experiencing postpartum depression or pain. It aims to understand how ketamine, used here for its potential mood-lifting and pain-relieving effects, behaves in the body after pregnancy. Non-pregnant women and men will serve as controls to compare results.

Inclusion Criteria

* Cesarean delivery

* Term delivery ≥ 37 weeks gestation anticipated at time of delivery

* ASA PS 2 or 3

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a ketamine infusion for 12 hours after cesarean delivery, with a 1-hour loading dose followed by an 11-hour maintenance dose

12 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety, pain, and depression scores post-infusion

12 weeks

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Ketamine

Trial Overview The study is testing how ketamine (Ketalar) is processed by the body (pharmacokinetics) and its effects (pharmacodynamics) in new mothers following a cesarean delivery compared to non-pregnant control subjects. The goal is to see if there's a difference in drug behavior due to post-pregnancy physiology.

Participant Groups

Group I: Ketamine Infusion: Healthy Control Population Experimental Treatment 1 Intervention

Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.

Group II: Ketamine Infusion: Cesarean Delivery Population Experimental Treatment 1 Intervention

Loading dose infusion for 1 hour followed immediately by maintenance dose infusion for 11 hours.

Who Is Running the Clinical Trial?

Grace Lim, MD, MS

Lead Sponsor

Trials

10

Recruited

660+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Subanaesthetic doses of ketamine have shown substantial efficacy in treating depression, with response rates averaging 77% and remission rates around 43% within 4 to 72 hours after a single dose.

Despite the rapid improvement in mood for many patients, the effects are often short-lived, highlighting the need for further research on dosing regimens and strategies to maintain the antidepressant response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Katalinic, N., Lai, R., Somogyi, A., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

S-ketamine as an adjuvant in patient-controlled intravenous analgesia for preventing postpartum depression: a randomized controlled trial. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective clinical trial. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Intraoperative ketamine for reduction in postpartum depressive symptoms after cesarean delivery: A double-blind, randomized clinical trial. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Prophylactic use of ketamine reduces postpartum depression in Chinese women undergoing cesarean section✰. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Ketamine as potential treatment for postpartum depression: A narrative review. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A randomized feasibility pilot-study of intravenous and subcutaneous administration of ketamine to prevent postpartum depression after planned cesarean delivery under neuraxial anesthesia. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

A single intravenous administration of a sub-anesthetic ketamine dose during the perioperative period of cesarean section for preventing postpartum depression: A meta-analysis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Ketamine Transfer Into Human Milk. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. [2013]