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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called brexanolone to assess its impact on depression in women undergoing perimenopause (the transition to menopause). The study aims to understand how allopregnanolone, a hormone-related substance and another name for brexanolone, affects mood and brain function during this period. Participants will receive either brexanolone or a placebo through a continuous IV (a tube that delivers medicine directly into the bloodstream) for 60 hours. Women experiencing depressive symptoms and not currently on depression medications might be suitable for this trial. As a Phase 4 trial, brexanolone has already received FDA approval and proven effective, and this research seeks to understand how it benefits more patients.

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.

What is the safety track record for brexanolone?

Research has shown that brexanolone is generally safe for use. Studies have found it can effectively reduce depression symptoms. The FDA has approved brexanolone for treating postpartum depression, confirming its safety for that purpose.

However, like any treatment, brexanolone can cause side effects. Previous trials reported that some participants experienced dizziness, sleepiness, or dry mouth, though these effects were usually mild. This is a Phase 4 trial, indicating that brexanolone has already passed earlier safety tests. Researchers are now studying its long-term effects and its efficacy for specific groups, such as women with perimenopausal depression. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Brexanolone is unique because it's specifically designed to target depression in perimenopausal women with a fast-acting approach. Unlike conventional antidepressants that can take weeks to become effective and often come in pill form, Brexanolone is administered as a continuous 60-hour intravenous infusion. This delivery method allows the treatment to potentially work within days, offering quicker relief for those struggling with severe depressive symptoms. Researchers are particularly excited about Brexanolone due to its promising mechanism of action that modulates GABA receptors, which are crucial for mood regulation, setting it apart from typical treatments that generally target serotonin pathways.

What is the effectiveness track record for Brexanolone in treating perimenopausal depression?

Research has shown that brexanolone, which participants in this trial may receive, can effectively treat postpartum depression, leading to quick and noticeable mood improvements compared to a placebo. This effect may occur because it influences levels of allopregnanolone, a hormone often lower in women with depression during menopause. Medicines like brexanolone have also shown promise for conditions such as premenstrual dysphoric disorder, which resembles depression during menopause. Based on these findings, brexanolone might help with depression during menopause by addressing hormonal imbalances. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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, 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]

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]

Citations

1. womensmentalhealth.org womensmentalhealth.org/posts/new-research-study-at-the-cwmh-a-novel-treatment-for-menopausal-depression/

New Research Study at the CWMH: A Novel Treatment ... Both preclinical and human data suggest that pregnenolone may be a promising treatment for depression. Dr. Freeman's study will test the effectiveness of ...

2. mghpsychnews.org mghpsychnews.org/new-study-will-investigate-novel-antidepressant-for-the-treatment-of-menopausal-depression/

New Study Will Investigate Novel Antidepressant for the ... Dr. Freeman's study will test the effectiveness of pregnenolone in women with menopausal depression. You can learn more about the study HERE.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6594874/

Allopregnanolone and Reproductive Psychiatry: An Overview Allopregnanolone and the Menopausal Transition​​ Depressed postmenopausal women have lower levels of ALLO than do healthy postmenopausal controls, and these ...

4. womensmentalhealth.org womensmentalhealth.org/posts/tag/brexanolone/

brexanolone Neuroactive steroids, derivatives of allopregnanolone, may be effective for the treatment of premenstrual dysphoric disorder.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8146562/

Brexanolone to Treat Postpartum Depression in Adult Women Brexanolone infusion resulted in rapid-onset, clinically significant, and durable reductions in HAM-D scores as compared to placebo.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02942004

NCT02942004 | A Study to Evaluate Efficacy and Safety of ... A negative change from baseline indicates less depression. A positive change from baseline indicates more depression. Baseline, Hour 60. Secondary Outcome ...