Brexanolone for Post-Traumatic Stress Disorder

Overseen by Donald J Newport, MD

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Donald Jeffrey Newport

Must not be taking: Benzodiazepines, CNS depressants

Disqualifiers: Pregnancy, Renal failure, Bipolar, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests if an IV drip of brexanolone can reduce PTSD symptoms in adult women who have experienced non-military trauma. The study will also check the safety of the treatment and its effects on depression and daily functioning. Participants will be monitored closely throughout the process. Brexanolone is the first therapy approved by the US FDA for the treatment of postpartum depression (PPD) in adults.

Will I have to stop taking my current medications?

The trial requires that if you are taking psychotropic medications, they must be at a stable dose for at least 14 days before the study and until 72 hours after the study drug infusion. You cannot start any new antidepressant or anti-anxiety medications until after the 72-hour assessments are completed.

Is brexanolone safe for humans?

Brexanolone, used for postpartum depression, is generally safe but can cause side effects like sleepiness, dizziness, and headaches. A small number of people may experience excessive sleepiness or fainting, so monitoring is required during treatment. ^{1 2 3 4 5}

How is the drug Brexanolone unique for treating PTSD?

Brexanolone is unique because it is an intravenous drug that acts as a neuroactive steroid, specifically targeting GABAA receptors in the brain, which is different from most oral medications used for PTSD. It was originally developed for postpartum depression, highlighting its novel mechanism of action in modulating brain chemistry. ^{1 2 3 4 5}

Research Team

Donald J Newport, MD

Principal Investigator

University of Texas at Austin/ Dell Medical School

Eligibility Criteria

This trial is for premenopausal women aged 18-50 with PTSD from civilian trauma, fluent in the test language, and in good health. Participants must not be pregnant or breastfeeding, have a stable psychotropic medication dose if any, and agree to use effective birth control during the study.

Inclusion Criteria

I have been diagnosed with PTSD from a civilian trauma.

Subject has signed an ICF prior to any study-specific procedures being performed

Subject agrees to adhere to the study requirements

Exclusion Criteria

I am not starting any new mental health medications within 2 weeks of screening.

History of an active substance use disorder in the 6 months prior to screening

I have a history of seizures.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive continuous IV infusion of brexanolone over a 24-hour period

30 hours

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

5 visits (telemedicine)

Treatment Details

Interventions

• Brexanolone Injection [Zulresso] (Corticosteroid)

Trial Overview The study tests Brexanolone Injection [Zulresso], given intravenously over 60 hours to see if it reduces PTSD symptoms severity based on PCL-5 scores and improves sleepiness and depression scales without causing significant side effects.

Participant Groups

Group I: Open-Label Infusion of Brexanolone Experimental Treatment 1 Intervention

This is a single arm pilot study of open label brexanolone delivered intravenously over a continuous 60-hour period. Infusions will be administered in a certified healthcare setting in accordance with the Zulresso™ dosing, administration and safety guidelines.

Who Is Running the Clinical Trial?

Donald Jeffrey Newport

Lead Sponsor

Trials

1

Recruited

20+

Sage Therapeutics

Industry Sponsor

Trials

51

Recruited

11,000+

Founded

2010

Headquarters

Cambridge, USA

Known For

Brain Health Medicines

Top Products

ZURZUVAE (zuranolone), SAGE-324

Findings from Research

Brexanolone (ZULRESSO™) is an intravenously administered treatment specifically designed for postpartum depression (PPD), acting as a positive allosteric modulator of GABAA receptors, which helps enhance inhibitory neurotransmission in the brain.

Approved in March 2019, brexanolone is a formulation that combines allopregnanolone, a natural neurosteroid, with a solubilizing agent, marking a significant advancement in the treatment options available for adult women suffering from PPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. Scott, LJ.[2020]

A pharmacovigilance study identified 267 cases of adverse drug reactions (ADRs) associated with brexanolone, with a significant number of reports related to psychiatric and nervous system issues, indicating a need for further investigation into these effects.

Serious outcomes were reported in 11.61% of patients using brexanolone, highlighting potential safety concerns that warrant additional prospective research to clarify the drug's safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). Zhang, M., Xie, W., Li, J., et al.[2023]

ZULRESSO (Brexanolone) is an FDA-approved treatment specifically for moderate-to-severe postpartum depression, highlighting the role of neurosteroids like allopregnanolone in managing this condition.

While brexanolone shows efficacy in alleviating depressive symptoms, it remains uncertain whether its effects last beyond 30 days after treatment, indicating a need for further research to assess long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone to Treat Postpartum Depression in Adult Women. Cornett, EM., Rando, L., Labbé, AM., et al.[2023]

Zulresso (brexanolone) is the only FDA-approved treatment for postpartum depression (PPD) and works by stimulating specific GABAA receptors in the brain, but its long infusion time and high cost can be barriers to use.

The study suggests that barbiturates and pyrazolopyridines, which also target the same GABAA receptors, could be repurposed as safer and more cost-effective alternatives for treating PPD, despite concerns about dependence with barbiturates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. Horwitz, AB., Rubin, RT.[2023]

Brexanolone (Zulresso) is an effective new treatment for postpartum depression (PPD), showing significant reductions in depression scores compared to placebo in clinical trials, particularly at doses of 60 and 90 μg/kg/hour.

While brexanolone has promising efficacy, it carries risks of somnolence and loss of consciousness, necessitating a Risk Evaluation and Mitigation Strategies (REMS) program to ensure patient safety during its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. Leader, LD., O'Connell, M., VandenBerg, A.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Brexanolone: First Global Approval. [2020]

2. Austria pubmed.ncbi.nlm.nih.gov

Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Brexanolone to Treat Postpartum Depression in Adult Women. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Barbiturates and pyrazolopyridines for the treatment of postpartum depression-repurposing of two drug classes. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. [2020]