Brexanolone for Depression in Perimenopausal Women

Overseen By Aleta Wiley

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Must not be taking: Antidepressants, Hormone therapy, others

Disqualifiers: Psychiatric illnesses, Suicidal ideation, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 hours

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This study aims to identify how the progesterone metabolite allopregnanolone affects behavior and neurobiology that may underlie perimenopausal depression.

Will I have to stop taking my current medications?

The trial requires that participants do not use medications to treat depression or systemic hormone therapy. If you are taking these, you would need to stop before joining the study.

Is brexanolone safe for use in humans?

Brexanolone, also known as Zulresso, has been approved for treating postpartum depression and is generally safe, but it can cause side effects like sleepiness, dizziness, and headaches. A small number of people may experience excessive sleepiness or fainting, so it must be given by a healthcare provider in a certified facility to ensure safety. ^{1 2 3 4 5}

What makes the drug Brexanolone unique for treating depression in perimenopausal women?

Brexanolone is unique because it is administered intravenously over 60 hours and works as a neuroactive steroid that modulates GABAA receptors, which is different from most oral antidepressants. It was originally developed for postpartum depression, highlighting its novel mechanism of action compared to traditional treatments. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for healthy perimenopausal women aged 40 to 60 who are experiencing depressive symptoms. Participants must be able to understand basic math and give informed consent. They cannot have sleep disorders, be on hormone therapy or certain medications, have severe psychiatric illnesses other than depression, unstable health conditions, liver/kidney issues, allergies to progesterone-related compounds, significant head injuries, intellectual disabilities or substance use disorders.

Inclusion Criteria

Ability to provide written informed consent

I am experiencing symptoms of depression.

Ability to read Arabic numerals and perform simple arithmetic

Exclusion Criteria

Inability to comply with study procedures

Investigator judgement that study participation constitutes substantial risk given medical or psychiatric condition

I am taking medication for depression.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a continuous 60-hour intravenous infusion of brexanolone or placebo

60 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 days

Treatment Details

Interventions

• Brexanolone
• Placebo

Trial Overview The study is testing the effects of a progesterone metabolite called allopregnanolone (given as brexanolone) versus a placebo in managing depression during perimenopause. It aims to understand how this compound influences behavior and brain function related to depression at this stage of life.

Participant Groups

Group I: brexanolone Experimental Treatment 1 Intervention

Participants will receive a continuous 60-hr intravenous infusion of brexanolone

Group II: placebo Placebo Group 1 Intervention

Participants will receive a continuous 60-hr infusion of placebo

Brexanolone is already approved in United States for the following indications:

Approved in United States as Zulresso for:

• Postpartum Depression

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

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]

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]

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]

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]

Brexanolone (Zulresso) was approved by the FDA for treating postpartum depression in adult women, based on three clinical trials that demonstrated its efficacy, particularly for treatment-resistant symptoms.

The drug must be administered in a certified healthcare facility under a special program, highlighting its safety measures and the importance of professional oversight during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone for the treatment of patients with postpartum depression. Morrison, KE., Cole, AB., Thompson, SM., et al.[2023]

Brexanolone, an injectable formulation of allopregnanolone, has been shown to be safe and effective for treating moderate to severe postpartum depression, based on three clinical trials that confirmed its efficacy and acceptable safety profile.

While brexanolone has a novel mechanism of action and is well tolerated, its use may be limited by high costs and potential serious side effects, such as loss of consciousness and excessive sedation, necessitating continuous monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexanolone: A Novel Drug for the Treatment of Postpartum Depression. Patatanian, E., Nguyen, DR.[2022]

References

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

Brexanolone: First Global Approval. [2020]

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

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

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

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

4. Austria pubmed.ncbi.nlm.nih.gov

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

5. Spain pubmed.ncbi.nlm.nih.gov

Brexanolone for the treatment of patients with postpartum depression. [2023]

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

Brexanolone: A Novel Drug for the Treatment of Postpartum Depression. [2022]