Dynamic Neural Mechanisms of Brexanolone-induced Antidepressant Effects in Postpartum Depression

Study Overview
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Brief Summary
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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.

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

Conditions
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Postpartum Depression

Intervention / Treatment
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* Drug: Brexanolone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Brexanolone|Enrolled subjects will receive a 60-hour infusion of Brexanolone (BRX) according to FDA approved protocol for administration. A programmable peristaltic infusion pump will be used to ensure accurate delivery.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of successfully analyzed EEG recordings | Feasibility of EEG recordings | 4 days | 
| Number of subjects completing the entire study protocol through the follow-up phase | Feasibility of study completion | 7 weeks | 
| Number of subjects withdrawn from protocol due to adverse events or participation burden | Feasibility of subject burden | 7 weeks |