This is an open-label, proof of concept trial to investigate the efficacy, safety and tolerability of Zulresso (brexanolone) administered to adult female subjects diagnosed with postpartum psychosis. This study will provide critical pilot data to determine whether there is similar treatment efficacy among patients with postpartum psychosis as observed to date in patients with postpartum depression.

This is a single site, open label study design to evaluate the efficacy, safety and tolerability of Zulresso in female subjects diagnosed with postpartum psychosis.

Participants will be consented, and if possible, participation will be discussed with available family members. Participants will take a consent questionnaire prior to consenting to ensure the voluntary nature and understanding of study procedures. Participants will undergo a screening visit including diagnostic interviews, clinical laboratory assessments and an EKG to determine eligibility. If eligible, participants will be admitted in-patient to UNC Hospitals and administered a continuous 60-hour infusion of Zulresso using the approved FDA REMS protocol for postpartum depression. A target dose of 90 μg/kg/hour will be administered over a period of 2.5 days following a strict tapering schedule. Monitoring will occur for an additional 12 hours after the infusion. The subject will participate in 6 follow up visits at day 7 post-infusion, day 14, day 21, day 30, day 60 and day 90.

Inclusion Criteria:

• All participating subjects sign an informed consent form;
• Age 18-45 years old;
• Onset of affective psychosis or mania symptoms in the 3rd trimester, within 4 weeks of delivery, or within 4 weeks of weaning;
• Clinician diagnosis of affective psychosis or mania;
• ≤12 months postpartum at screening

Exclusion Criteria:

• Positive pregnancy test at screening or day 1;
• Recent pregnancy did not result in a live birth;
• Subject is in renal failure;
• Subject is in hepatic failure;
• Subject is anemic (hemoglobin ≤10 g/dL);
• Untreated or inadequately treated hypothyroidism or hyperthyroidism;
• History of schizophrenia, and/or schizoaffective disorder;
• Current/active alcohol or drug abuse

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Data will be available by investigator request starting 9 months following publication and continue through 36 months afterwards.

Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.