The Perinatal Synergistic Multi-component Intervention to alLeviate dEpressive Symptoms. A Case Series

NCT06048263 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 202306156
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open label case series is to learn about the feasibility of conducting a future randomised controlled trial to evaluate how well the Perinatal SMILES intervention works in improving post-cesarean mood in low-income women. The main questions it aims to answer are:

1. 1.Is it feasible to recruit a sufficient number of participants?
2. 2.Is it feasible to administer Perinatal SMILES and
3. 3.Is it feasible to collect participant outcomes?
4. 4.Complete five sessions of interpersonal therapy
5. 5.Receive two skin injections of ketamine, approximately 24 hours apart, in the first four postpartum day
6. 6.Receive additional therapy sessions before (to prepare for ketamine) and after (interpersonal therapy) each ketamine injection
7. 7.Undergo assessments of brain electrical activity (at rest and evoked by trans-cranial magnetic stimulation) before and at three timepoints in the 10 hours after each ketamine injection
8. 8.Complete mood assessments over the first 12 postpartum weeks

Conditions

Postpartum Depression

Keywords

Pregnancy; Socio-economically disadvantaged; Cesarean; Postpartum depression

Outcome Measures

Primary Outcomes (20)

• Depressive symptoms

  These will be assessed using the Edinburgh Postpartum Depression Scale (EDPS) questionnaire.30 The EPDS is a set of ten questions about the subject's mood in the previous seven days. Each symptom is scored on a numeric rating scale of none (0) to severe (3). Commonly employed thresholds for psychiatric referral are 10-13 out of a possible 30 points.

  through postoperative day 84

• P30 (TMS-evoked potential)

  This will be assessed using TMS-EEG. The amplitude of each of component positive (P) and negative (N) deflections in the evoked EEG signal will be recorded before and at 3 timepoints in the 2-10 hours after ketamine. The component deflections are named according to polarity of the deflection (N = negative, P = Positive) and the approximate time in milliseconds after the TMS input. For example N45 is the negative deflection observed approximately 45 ms after the TMS input.

  4 days

• N45 (TMS-evoked potential)

  This will be assessed using TMS-EEG. The amplitude of each of component positive (P) and negative (N) deflections in the evoked EEG signal will be recorded before and at 3 timepoints in the 2-10 hours after ketamine. The component deflections are named according to polarity of the deflection (N = negative, P = Positive) and the approximate time in milliseconds after the TMS input. For example N45 is the negative deflection observed approximately 45 ms after the TMS input.

  4 days

• P60 (TMS-evoked potential)

  This will be assessed using TMS-EEG. The amplitude of each of component positive (P) and negative (N) deflections in the evoked EEG signal will be recorded before and at 3 timepoints in the 2-10 hours after ketamine. The component deflections are named according to polarity of the deflection (N = negative, P = Positive) and the approximate time in milliseconds after the TMS input. For example N45 is the negative deflection observed approximately 45 ms after the TMS input.

  4 days

• N100 (TMS-evoked potential)

  This will be assessed using TMS-EEG. The amplitude of each of component positive (P) and negative (N) deflections in the evoked EEG signal will be recorded before and at 3 timepoints in the 2-10 hours after ketamine. The component deflections are named according to polarity of the deflection (N = negative, P = Positive) and the approximate time in milliseconds after the TMS input. For example N45 is the negative deflection observed approximately 45 ms after the TMS input.

  4 days

• Cortical evoked activity (CEA)

  The CEA will be calculated from the area under the curve of the rectified single pulse TMS-evoked potential

  4 days

• Anxiety

  This will be assessed using the General Anxiety Disorder-7 (GAD-7) questionnaire. There are 7 items scored from 0-3. The total score can range from 0 (no anxiety) - 21 (most anxiety).

  through postoperative day 84

• Psychosocial stress

  This will be assessed using the Antenatal Risk Questionnaire (ANRQ). The range of scores is 5-60. A higher score indicates greater psychosocial risk.

  at enrollment 1 day

• Post-Traumatic Stress Disorder (PTSD)

  The Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) questionnaire. Scores range 0 - 80. More severe PTSD scores higher.

  through postoperative day 84

• Obstetric Quality of Recovery

  (ObsQoR10 score, 10 items, total score 0-100)

  through postoperative day 84

• Number of participants who successfully breastfeed their newborn baby

  Success in any 24-hour period will be defined as when an infant breastfeeds, for 10 minutes or more in a rhythmic suck/swallow/pause/suck pattern, at least eight times in that 24-hour period.

  4 days

• Adverse effects - sedation

  Will be assessed on a four point scale (Not present, mild, moderate, severe): sedation.

  4 days

• Adverse effects - Blurred vision

  Will be assessed on a four point scale (Not present, mild, moderate, severe): blurred vision.

  4 days

• Adverse effects - diplopia

  Will be assessed on a four point scale (Not present, mild, moderate, severe): diplopia.

  4 days

• Adverse effects - dizziness

  Will be assessed on a four point scale (Not present, mild, moderate, severe): dizziness.

  4 days

• Adverse effects - euphoria

  Will be assessed on a four point scale (Not present, mild, moderate, severe): euphoria.

  4 days

• Adverse effects - amnesia

  Each of the following will be assessed on a four point scale (Not present, mild, moderate, severe): amnesia.

  4 days

• Adverse effects - hallucinations

  Will be assessed on a four point scale (Not present, mild, moderate, severe): hallucinations.

  4 days

• Adverse effects - nystamus

  Will be assessed on a four point scale (Not present, mild, moderate, severe): nystagmus.

  4 days

• Antidepressant treatment

  All current pharmacological and psychological therapies will be documented.

  through postoperative day 84

Study Arms (1)

Intervention Interpersonal psychotherapy plus ketamine

EXPERIMENTAL

Five sessions of interpersonal psychotherapy (IPT) and pre-, and post-, ketamine sessions b) Two doses of subcutaneous (SC) ketamine in the first 4 post-cesarean days

Behavioral: interpersonal psychotherapy (IPT); Drug: Ketamine

Interventions

interpersonal psychotherapy (IPT) BEHAVIORAL

The ROSE intervention is a five-session intervention developed to build communication skills, improve social support, and improve stress management. It is easy to learn and does not require a healthcare professional or mental health specialist to deliver. For this study, the investigators plan to deliver to individuals during inpatient visits, in-person appointments or via telemedicine (phone or videoconference), as appropriate or per participant preference. The first four sessions are approximately 60 minutes in length.

Also known as: Reach Out Stay Strong Essentials (ROSE) IPT

Intervention Interpersonal psychotherapy plus ketamine

Ketamine DRUG

During the first four post-cesarean days, the investigators will administer subcutaneous ketamine (0.5 mg/kg) and a repeated dose of 0.5 or 0.7 mg/kg \~24 hours later (the second dose will be increased to 0.7 mg/kg if no severe adverse effects are reported after the first dose and the patient is in agreement with the dose escalation).

Also known as: Subcutaneous Ketamine

Intervention Interpersonal psychotherapy plus ketamine

Eligibility Criteria

• Gender Eligibility Details: Must be \>20 weeks pregnant
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• English-speaking (necessary for IPT under the limitations of the pilot) Socio-economically disadvantaged (i.e., low-income requiring public assistance) Suffering with depressive symptoms (EPDS \> 10) \>18 years of age \> 20 weeks pregnant scheduled for cesarean delivery" or "within 48 hours of an unscheduled (or scheduled) cesarean delivery.

You may not qualify if:

• An allergy to ketamine
• Contraindications for TMS including the presence of metallic objects within 30 cm of the TMS coil, intracranial implants (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed; presence of intracardiac lines, defibrillators or a cardiac pacemaker and unable to assess safety; presence of implanted electronic devices that control physiologic functions and unable to assess safety
• Have a personal history of a primary seizure disorder or a seizure associated with an intracranial lesion
• History of severe head trauma or neurological disorders (e.g., pre-eclampsia) that substantially increase seizure risk, per PI discretion

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depression, Postpartum

Interventions

Interpersonal Psychotherapy; adenylate isopentenyltransferase; Ketamine

Condition Hierarchy (Ancestors)

Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• David Monks, MBCHB

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc Prof of Anesthesiology, Anesthesiology

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: September 21, 2023
• Study Start: October 15, 2025
• Primary Completion: October 15, 2025
• Study Completion: October 15, 2025
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)