Dynamic Neural Mechanisms of Brexanolone-induced Antidepressant Effects in Postpartum Depression (BRX-PPD)

Dynamic Neural Mechanisms of Brexanolone-induced Antidepressant Effects in Postpartum Depression: a Feasibility Study

This is a feasibility study of performing repeated EEG recordings and assessment of affective states during open-label administration of BRX to women with postpartum depression. Study phases will include screening, enrollment, intervention, and follow-up. Subjects will be screened for study eligibility criteria through clinical assessments and self-report. Enrolled subjects will be admitted to the UNC Women's Hospital, where five serial EEG recordings will be obtained, along with frequent assessments of affective state, before, during, and after a 60-hour IV infusion of BRX. Follow-up procedures will include assessments of PPD and affective symptoms, as well as an exit interview with the study team. If feasibility outcomes are achieved, exploratory EEG analyses will be performed with AMICA (adaptive mixture independent component analysis), community detection, and microstate assessment. Exploratory analyses of data collected by facial expression detection software (iMotions Affectiva) are also planned.

Study Overview

• Status: Completed
• Conditions: Postpartum Depression
• Intervention / Treatment: Drug: Brexanolone

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women with moderate to severe PPD, medically eligible to receive FDA-approved BRX infusion, recruited from current inpatient and outpatient population in the Women's Mood Disorders Clinic at UNC and through local advertisements. Subjects recruited from outpatient setting will be individuals for whom BRX is the chosen recommended course of treatment.

Description

Inclusion Criteria:

• Signed informed consent.
• Documented proof of full COVID-19 vaccination
• Ambulatory, female, aged 18-45
• ≤ 8 months postpartum
• Agrees to adhere to the study requirements.
• Onset of depression in 3rd trimester or within 4 weeks of delivery
• Meets DSM-V criteria for major depressive disorder with peripartum onset.
• 17-item HAM-D total score ≥20 at screening
• Stopped breastfeeding or agrees to temporarily stop for 7 days including 4 days of hospitalization and 3 days after
• No new psychotropic drugs during screening and active treatment of study
• Stable use of any current psychotropic drugs for at least 28 days prior to enrollment, with stable dosage for at least 14 days prior to enrollment
• Must be on documented contraceptive.
• Must have a caregiver or family member with them to help care for the subject's child(ren) during the infusion and to be in the room with the subject if the child(ren) are present during the infusion

Exclusion Criteria:

• Positive pregnancy test at screening or day 1
• Pregnancy that resulted in a stillbirth, termination, or child that was placed for adoption.
• Renal impairment or failure, hepatic impairment or failure, or anemia
• Untreated or inadequately treated hypothyroidism or hyperthyroidism
• Known allergy to progesterone or allopregnanolone.
• Suicide attempt at this episode
• Medical history of schizophrenia, and/or schizoaffective disorder
• Current psychotic symptoms including delusions, hallucinations, or formal thought disorder.
• Concurrent substance abuse
• Exposure to another investigational medication or device within 30 days
• Has previously participated in any study employing brexanolone or SAGE-217.
• Subject is investigative site personnel, sponsor personnel, or an immediate member of their family.
• Has received electroconvulsive therapy during current episode.
• History of seizure disorder
• On anticonvulsant agents
• On benzodiazepines

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Successfully Analyzed EEG Recordings	Feasibility of EEG recordings. Each participant was scheduled to have 5 EEG recordings.	4 days
Number of Subjects Completing the Entire Study Protocol Through the Follow-up Phase	Feasibility of study completion	30 days
Number of Subjects Withdrawn From Protocol Due to Adverse Events or Participation Burden	Feasibility of subject burden	30 days

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Sage Therapeutics; Baszucki Brain Research Fund
• Investigators: Principal Investigator: Susan Girdler, PhD, UNC Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Behavioral Symptoms; Mood Disorders; Puerperal Disorders; Depression; Depressive Disorder; Depression, Postpartum; Neurosteroids; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; GABA Modulators; GABA Agents; Brexanolone
• Other Study ID Numbers: 21-2224

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No