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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how ketamine, a medication sometimes used for pain and depression, works in women who have just had a cesarean delivery compared to others. Researchers seek to determine if ketamine behaves differently in the body after childbirth, focusing on its processing and effects. The trial includes two groups: women who have had a cesarean delivery and healthy men and women who have not recently been pregnant. Women who have recently had a cesarean delivery and are not planning to breastfeed or need ketamine for pain management might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that ketamine can help prevent postpartum depression after a cesarean delivery. Research indicates that it is generally well-tolerated for this purpose. However, caution surrounds its use during pregnancy due to insufficient safety information. Since this trial involves women who have just given birth, the focus is on how the body processes the drug post-childbirth, which may differ from other times. While researchers continue to study ketamine, past trials suggest it can be used safely in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for postpartum depression?

Most treatments for postpartum depression, like antidepressants and psychotherapy, can take weeks to show effectiveness. Ketamine is unique because it acts much faster, potentially delivering relief within hours. Researchers are excited about ketamine's ability to target the brain's glutamate system, which is different from traditional options that typically focus on serotonin. This new mechanism of action could provide quicker, more effective relief for new mothers struggling with postpartum depression.

What evidence suggests that ketamine might be an effective treatment for postpartum depression?

Research has shown that ketamine might help treat postpartum depression. Some studies found that ketamine can quickly ease depression symptoms, providing fast relief for new mothers. In this trial, participants will receive ketamine infusions, with one group consisting of a healthy control population and another group consisting of a cesarean delivery population. Early findings suggest that ketamine changes certain chemical signals in the brain, which can lift mood. More research is needed to understand ketamine's effectiveness specifically for postpartum depression, but initial results are promising. ^{1 5 6 7 8}

Who Is on the Research Team?

Grace Lim, MD, MSc

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. samhsa.gov samhsa.gov/

Home | SAMHSA - Substance Abuse and Mental Health ... SAMHSA leads efforts to advance behavioral health across the U.S., offering resources for mental health, substance use, and community well-being.

2. bmcpregnancychildbirth.biomedcentral.com bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-025-07186-y

Efficacy and safety of ketamine and esketamine in reducing ... Postpartum depression (PPD) is categorized by the Disorders-Fifth Edition as depression that begins during pregnancy or within the first ...

3. womensmentalhealth.org womensmentalhealth.org/posts/ketamine-esketamine-for-postpartum-depression/

Is Ketamine or Esketamine an Option for the Treatment ... Further studies are needed to determine whether ketamine and esketamine are effective for the treatment of postpartum depression.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032724002210

Effects of ketamine and esketamine on preventing ... Postpartum depression (PPD) is defined as depressive disorder that occurs during pregnancy or within 4 weeks following delivery by the ...

5. bmj.com bmj.com/content/385/bmj-2023-078218

Efficacy of a single low dose of esketamine after childbirth ... At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11994625/

Ketamine and Perinatal Mental Health ... postpartum use, and guidelines caution that “likely patients should not use it during pregnancy until further safety data are available.

7. nature.com nature.com/articles/s41380-025-03320-6

Efficacy and safety of esketamine on major depression ... In conclusion, our findings demonstrate that esketamine is effective in treating MDD/TRD and preventing PPD and postoperative depression.

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830227

Intraoperative Esketamine and Postpartum Depression ... This randomized clinical trial evaluates the effect of esketamine infusion during cesarean delivery on postpartum depression 6 weeks after ...