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

The Perinatal SMILES (Synergistic Multi-component Intervention to alLeviate dEpressive Symptoms) Case Series. Combining Ketamine and Interpersonal Psychotherapy to Improve Postpartum Mood

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. Is it feasible to recruit a sufficient number of participants?
2. Is it feasible to administer Perinatal SMILES and
3. Is it feasible to collect participant outcomes?

To profile EEG in participants at rest and in response to TMS, before and after subcutaneous ketamine

Participants will:

1. Complete five sessions of interpersonal therapy
2. Receive two skin injections of ketamine, approximately 24 hours apart, in the first four postpartum day
3. Receive additional therapy sessions before (to prepare for ketamine) and after (interpersonal therapy) each ketamine injection
4. 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
5. Complete mood assessments over the first 12 postpartum weeks

Study Overview

• Status: Not yet recruiting
• Conditions: Postpartum Depression
• Intervention / Treatment: Behavioral: interpersonal psychotherapy (IPT); Drug: Ketamine

Detailed Description

The investigators will perform an open-label case series to evaluate the feasibility of performing a trial of a novel intervention to reduce postpartum depression symptoms after cesarean delivery. The intervention, Perinatal SMILES (Synergistic Multi-component Intervention to alLeviate dEpressive Symptoms), combines interpersonal therapy with subcutaneous ketamine therapy. The interpersonal therapy consists of five sessions that will be administered during the antepartum and/or postpartum. The ketamine therapy will be administered as two injections, approximately 24 hours apart, in the first four postpartum days and will be preceded and followed by additional therapy sessions. The investigators will assess brain electronic activity before and after the ketamine injections and mood in the first 12 postpartum weeks. The objective is to determine the feasibility of recruiting participant, administering the intervention and collect the outcome data.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: David Monks, MBCHB; Phone Number: 314-323-1845; Email: dmonks@wustl.edu
• Study Contact Backup: Name: Haley Bernstein; Phone Number: 314-747-6073; Email: bernstein.h@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

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.

Exclusion Criteria

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention Interpersonal psychotherapy plus ketamine; 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); 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.; Other Names: Reach Out Stay Strong Essentials (ROSE) IPT; Drug: Ketamine; 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).; Other Names: Subcutaneous Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
Obstetric Quality of Recovery	(ObsQoR10 score, 10 items, total score 0-100)	through postoperative day 84

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: David Monks, MBCHB, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Cesarean; Postpartum depression; Socio-economically disadvantaged
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Pregnancy Complications; Puerperal Disorders; Depressive Disorder; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depression; Depression, Postpartum; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 202306156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No