What Is Brexanolone?
Brexanolone is an FDA-approved medication for postpartum depression. It is a synthetic form of allopregnanolone, a naturally occurring neurosteroid in the brain that plays a role in mood regulation. By acting on specific brain receptors, brexanolone is thought to help restore balance in brain activity that may be disrupted in conditions like postpartum depression.
Beyond its approved use, brexanolone is also being investigated for its potential to treat other conditions, including alcohol use disorder, depression, post-traumatic stress disorder, and postpartum psychosis. Researchers are exploring how its mechanism of action might benefit patients with various neurological and psychiatric conditions.
Uses and Conditions Under Study
Brexanolone is currently being studied in 11 clinical trials involving a total of 174 participants. While it is FDA-approved for postpartum depression, researchers are exploring its potential in several other areas.
-
Postpartum Mood Disorders: Brexanolone is primarily known for its use in postpartum depression, a serious mood disorder that can occur after childbirth. It is also being studied for postpartum psychosis, a more severe psychiatric emergency. A total of 5 trials are investigating brexanolone for these conditions, building on its established role in addressing mood changes related to reproductive steroid dynamics.
-
Alcohol Use Disorder (AUD): Brexanolone is being investigated for alcohol use disorder, a condition characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. The drug's influence on brain neurosteroids may offer a new approach to managing withdrawal symptoms or cravings. Two trials are exploring its efficacy in this area.
-
Other Mood and Anxiety Disorders: Researchers are also studying brexanolone for general depression and post-traumatic stress disorder (PTSD). These conditions involve dysregulation of mood and stress responses, which might be influenced by brexanolone's action on neurosteroid pathways. Four trials are dedicated to understanding its role in these broader mental health challenges.
-
COVID-19: In one trial, brexanolone is being explored in the context of COVID-19. While the specific rationale is not detailed, some research has investigated the role of neurosteroids in inflammatory responses or neurological symptoms associated with viral infections. One trial is currently examining this potential use.
Dosing
Brexanolone is administered as a continuous intravenous (IV) infusion under medical observation. The specific dosage and duration of infusion can vary depending on the condition being treated and the study protocol.
For its FDA-approved use in postpartum depression, brexanolone is typically given as a continuous IV infusion over 60 hours, with the dose titrated up to a maximal dose of 90 mcg/kg/hr, following an FDA-approved protocol.
In clinical trials, various dosing regimens have been studied for different conditions. These include:
-
A 20-hour intravenous infusion at doses of 90 mcg/kg/hr, 60 mcg/kg/hr, or 30 mcg/kg/hr.
-
An open-label infusion of brexanolone, where the specific dose may be adjusted based on individual patient needs or study design.
All brexanolone infusions require careful medical supervision due to the nature of the drug and its administration.
Side Effects
In clinical trials, patients taking Brexanolone experienced various side effects. The most common side effect was septic shock, which occurred in 28.6% of patients taking Brexanolone, compared to 0.0% on placebo. Other common side effects included:
- Delirium: 21.4% of patients on Brexanolone experienced delirium, compared to 0.0% on placebo.
- Infusion site pain: 15.0% of patients on Brexanolone experienced pain at the infusion site, compared to 0.0% on placebo.
- Constipation: 14.3% of patients on Brexanolone experienced constipation, which was the same rate as 14.3% on placebo.
- Blistering: 14.3% of patients on Brexanolone developed blisters, compared to 0.0% on placebo.
- Sedation: 10.0% of patients on Brexanolone experienced sedation, compared to 0.0% on placebo.
- Dizziness: 10.0% of patients on Brexanolone experienced dizziness, compared to 0.0% on placebo.
- Nausea: 8.8% of patients on Brexanolone experienced nausea, compared to 4.5% on placebo.
Less common side effects reported in patients taking Brexanolone included decubitus ulcer (7.1% vs 0.0% on placebo), Escherichia sepsis (7.1% vs 0.0% on placebo), bradycardia (7.1% vs 0.0% on placebo), and enterococcal bacteraemia (7.1% vs 0.0% on placebo).
Clinical Trial Results
Brexanolone has been studied in several clinical trials for various conditions, including postpartum depression, acute respiratory distress syndrome, and tinnitus.
Postpartum Depression (PPD) in Adolescent Females
A study (NCT03665038) evaluated the safety and how Brexanolone moves through the body (pharmacokinetics) in adolescent females with postpartum depression. In the double-blind phase of the study, 3 participants taking Brexanolone and 4 participants taking placebo experienced treatment-emergent adverse events. In the open-label phase, 5 participants taking Brexanolone experienced treatment-emergent adverse events. Measurements of drug levels in the blood, such as peak concentration (Cmax) and half-life (Thalf), were also collected.
Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19
In a study (NCT04537806) investigating Brexanolone for ARDS due to COVID-19, 8 participants taking Brexanolone died through day 28, compared to 6 participants taking placebo. The percentage of participants who were alive and free of respiratory failure at day 28 was 23.1% for both the Brexanolone group and the placebo group, indicating no difference between the two groups for this outcome. Treatment-emergent adverse events were reported by 14 participants on Brexanolone and 13 participants on placebo.
Dynamic Neural Mechanisms in Postpartum Depression
An open-label study (NCT05543746) explored the neural effects of Brexanolone in postpartum depression. All 10 participants completed the entire study protocol through the follow-up phase, and no participants withdrew due to adverse events or the burden of participation. The study successfully analyzed 49 EEG recordings to understand brain activity changes.
Tinnitus
An open-label study (NCT05645432) evaluated Brexanolone in adults with tinnitus. Participants reported changes in their tinnitus symptoms using Visual Analog Scales (VAS). For annoyance (VAS-A) ratings, participants experienced a reduction from baseline, with observed mean scores decreasing by approximately 7.6 to 22.3 points after 6 hours of infusion. Similarly, for loudness (VAS-L) ratings, observed mean scores decreased by approximately 3.1 to 15.7 points after 6 hours of infusion. A reduction in scores indicates an improvement in symptoms. Daily diary measurements also showed sustained reductions in both annoyance and loudness ratings post-infusion. Only 1 participant experienced a treatment-emergent adverse event in this study.
Currently Recruiting Trials
For individuals interested in exploring new treatment options, Brexanolone is currently being investigated in a clinical trial actively seeking participants. These studies are crucial for understanding how new therapies can help patients with specific conditions and expand our knowledge of existing treatments.
One such opportunity is an open-label pilot study, NCT05254405, sponsored by Donald Jeffrey Newport. This Phase 4 study, titled "An Open Label Pilot Study of IV Brexanolone for the Treatment of Post-Traumatic Stress Disorder," is designed to evaluate Brexanolone's potential in a real-world setting. As a pilot study, it aims to gather preliminary data to inform larger future research efforts. Researchers are specifically looking at whether a 24-hour intravenous infusion of Brexanolone, administered at up to 60 μg/kg/h, can reduce the severity of PTSD symptoms. The study aims to enroll 20 adult women who have been diagnosed with post-traumatic stress disorder and are not veterans. This research focuses on understanding the potential benefits of Brexanolone for this specific patient group, building upon previous findings and exploring new applications.
Participants in this study will receive an open-label infusion of Brexanolone, meaning both the participants and the researchers will know the treatment being administered. The primary goal is to determine the effectiveness of the treatment in reducing PTSD symptom severity in this specific population. Eligibility criteria for this study include being female, between 18 and 50 years of age, and having a diagnosis of PTSD. It is important to note that healthy volunteers are not eligible, and the study is not designed for children, ensuring the focus remains on individuals directly affected by PTSD. This careful selection helps ensure the study results are relevant to the target patient population.
Where to Participate
The currently recruiting study for Brexanolone, focusing on Post-Traumatic Stress Disorder, is available at a single location. This approach allows researchers to concentrate efforts and resources in one dedicated site to thoroughly evaluate the treatment.
The study, NCT05254405, is actively enrolling participants in Austin, Texas. This site is the sole location for this particular research. To be eligible for participation, individuals must be female and fall within the age range of 18 to 50 years. The study specifically seeks participants with a diagnosis of Post-Traumatic Stress Disorder; healthy volunteers are not being recruited for this trial. Additionally, the study is not open to children.
Development Timeline
The journey of Brexanolone in clinical development began on September 11, 2018, with the initiation of its first clinical trial. Since then, a total of 11 clinical trials have been conducted or are ongoing, involving 174 participants across various studies.
Early development saw Brexanolone investigated for conditions such as IBS-C and hyperphosphatemia. Over time, the scope of research expanded significantly. Key sponsors like Supernus Pharmaceuticals, Inc., Sage Therapeutics, and the University of North Carolina, Chapel Hill, have played a pivotal role in driving its progression. The drug has moved through various phases of development, starting with Early Phase 1 and Phase 1 studies, advancing to Phase 2 and Phase 3 trials, and now includes Phase 4 studies, indicating its continued evaluation post-approval or in broader populations.
The pipeline for Brexanolone has diversified to address a wide range of conditions. Beyond its initial focus, studies have explored its potential in areas such as Alcohol Use Disorder (AUD), COVID-19, Depression, Post-Traumatic Stress Disorder (PTSD), Post Partum Depression, Postpartum Psychosis, Acute Respiratory Distress Syndrome, and Tinnitus. This broad exploration highlights the ongoing commitment to understanding Brexanolone's therapeutic potential across different medical needs. The latest trial is projected to conclude by August 30, 2024, marking continued progress in its development.