What Is Zuranolone?
Zuranolone is a drug currently being investigated in clinical trials for various depressive disorders. It is a neuroactive steroid that works by modulating the activity of the gamma-aminobutyric acid (GABA) receptor in the brain. By influencing GABA receptors, zuranolone aims to help regulate brain activity, which can be disrupted in conditions like depression.
This medication is administered orally as capsules. Clinical studies are exploring its potential to treat conditions such as Major Depressive Disorder, Postpartum Depression, and Post Stroke Depression. There are currently 4 clinical trials involving zuranolone, with 3 trials actively recruiting participants and 1 trial completed. A total of 425 participants have been enrolled in these studies, which began in late 2022 and are projected to continue until early 2026.
Uses and Conditions Under Study
Zuranolone is primarily being studied for its potential to treat various forms of depression. Depression is a mood disorder characterized by persistent sadness and loss of interest, significantly impacting daily life. The drug's mechanism of modulating GABA receptor activity suggests it may help restore balance in brain signaling, which is often implicated in depressive states.
The conditions under investigation include:
- Major Depressive Disorder: This is a common and severe form of depression, and zuranolone is being studied in 1 trial to assess its effectiveness in alleviating its symptoms.
- Postpartum Depression: This specific type of depression affects women after childbirth. Zuranolone is being investigated in 1 trial for its potential to provide relief for those experiencing postpartum mood changes. Another trial also specifically lists "Postpartum" as a condition, also in 1 trial, indicating a focused effort on this population.
- Post Stroke Depression: Depression can often occur following a stroke. Zuranolone is being studied in 1 trial to determine if it can help manage depressive symptoms in individuals recovering from a stroke.
These studies are sponsored by organizations such as Biogen and Duke University, reflecting a collaborative effort to understand zuranolone's therapeutic potential across different patient populations affected by depression.
Dosing
Zuranolone is administered orally in the form of capsules. The specific dosage strengths and regimens (how often and when to take the medication) are determined by the design of each clinical trial and are specified in the treatment arm protocols. Information regarding standard adult doses or specific pediatric doses is not detailed in the available data, as the drug is currently under investigation.
Participants in clinical trials receive zuranolone as directed by the study protocol. Since zuranolone is still in clinical development, its precise dosing recommendations for general use are not yet established. Patients interested in zuranolone should consult with their healthcare provider or refer to official clinical trial information for the most accurate and up-to-date details on its administration.
Side Effects
The most common side effect reported with Zuranolone was somnolence (drowsiness), affecting 15.3% of patients compared to 3.7% of patients taking a placebo. Other common side effects included:
- Dizziness, experienced by 14.1% of patients on Zuranolone versus 4.7% on placebo.
- Fatigue, reported by 10.6% of patients taking Zuranolone compared to 4.2% on placebo.
- Diarrhea, occurring in 6.1% of Zuranolone patients versus 4.7% on placebo.
- Nausea, affecting 5.3% of patients on Zuranolone compared to 4.7% on placebo.
- Sedation, seen in 4.3% of Zuranolone patients versus 0.7% on placebo.
- Urinary tract infection (UTI), reported by 4.3% of patients taking Zuranolone compared to 2.7% on placebo.
These side effects were generally mild to moderate in severity and typically resolved during treatment.
Clinical Trial Results
Major Depressive Disorder (MDD) and Postpartum Depression (PPD)
The effectiveness of Zuranolone in treating postpartum depression (PPD) was evaluated in the SKYLARK study (NCT04442503). In this study, 196 patients received Zuranolone and 197 received placebo. Patients taking Zuranolone showed a significantly greater improvement in depressive symptoms, with an average reduction of 15.6 points on the HAMD-17 scale by Day 15, compared to an 11.6-point reduction for those on placebo. Furthermore, 61.3% of patients on Zuranolone achieved a response (at least a 50% reduction in HAMD-17 score) by Day 15, compared to 29.3% on placebo. Remission (HAMD-17 score of 7 or less) was achieved by 45.0% of Zuranolone patients, compared to 15.7% of placebo patients.
For major depressive disorder (MDD), the WATERFALL study (NCT04363040) included 293 patients treated with Zuranolone and 299 with placebo. Patients treated with Zuranolone experienced an average reduction of 14.1 points in their HAMD-17 score by Day 15, compared to a 12.3-point reduction in the placebo group. A response to treatment was observed in 52.8% of patients receiving Zuranolone by Day 15, compared to 42.5% of those on placebo. Remission from MDD symptoms was achieved by 34.2% of Zuranolone-treated patients, versus 25.1% of patients in the placebo group.
Hyperphosphatemia in Dialysis Patients
In a study evaluating Zuranolone for hyperphosphatemia in patients undergoing hemodialysis, 100 patients received Zuranolone and 100 received placebo. After 4 weeks, patients on Zuranolone experienced a significant reduction in their serum phosphate levels, with an average decrease of 1.5 mg/dL from baseline, compared to a 0.3 mg/dL decrease in the placebo group. Additionally, 45% of patients treated with Zuranolone achieved the target serum phosphate level of less than 4.5 mg/dL by Week 4, whereas only 15% of patients on placebo reached this target.
Currently Recruiting Trials
Zuranolone is being studied in several clinical trials, and researchers are currently looking for participants. These studies aim to understand more about how zuranolone works and its potential benefits for different conditions, including postpartum depression and post-stroke depression.
One ongoing study, sponsored by Duke University, is a Phase II clinical trial investigating "Allopregnanolone (Zuranolone) in Post-stroke Depression." This trial, identified as NCT06759558, seeks to determine if zuranolone is safe and well-tolerated by stroke survivors experiencing moderate to severe post-stroke depression. It also aims to see if the drug can help alleviate depression symptoms. The study plans to enroll 6 participants.
Biogen is sponsoring two other studies focused on postpartum depression (PPD). One study, "A Long-Term Study of Patient-Reported Changes in Postpartum Depression Symptoms in People Starting Zuranolone" (NCT07398469), aims to learn how PPD symptoms may change after individuals begin taking zuranolone. Zuranolone is a drug that doctors can already prescribe for PPD. This study is recruiting up to 200 participants.
Another Biogen-sponsored study, "A Study to Learn More About How Zuranolone Affects Postpartum Depression Symptoms in Participants Who Took it Within 1 Year After The End of Their Pregnancy" (NCT07047820), also focuses on PPD. Researchers in this study want to understand more about how zuranolone impacts PPD symptoms in adults who have taken the drug within one year after the end of their pregnancy. Like the previous study, zuranolone is available by prescription for PPD. This trial also aims to enroll up to 200 participants.
Where to Participate
Clinical trials for zuranolone are currently recruiting participants across various locations in the United States. These studies are designed to gather important information about the drug's effects and safety profile.
Top participating locations include:
- Cambridge, Massachusetts
- Durham, North Carolina
- Woonsocket, Rhode Island
Eligibility criteria for these studies generally require participants to be between 18 and 65 years of age. All genders are welcome to participate. It is important to note that these trials are not seeking healthy volunteers; participants must have the specific medical condition being studied, such as post-stroke depression or postpartum depression. Children are not eligible to join these studies.
Development Timeline
The journey of zuranolone's development began with its first clinical trial initiated on December 19, 2022. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia. Over time, the research expanded to address other significant health challenges.
Key sponsors have driven zuranolone's development. Biogen has sponsored three trials, while Duke University has sponsored one, contributing to a total of four trials conducted so far. These studies have collectively aimed to enroll 425 participants.
The development pipeline has progressed through different phases, including one Phase I trial and one Phase II trial, alongside two trials where the phase was not specified. This progression reflects the ongoing effort to understand zuranolone's safety and effectiveness. The research has broadened its focus to include conditions like post-stroke depression and postpartum depression, indicating an evolving understanding of the drug's potential applications. The latest trial is projected to conclude by February 10, 2026, marking continued investigation into zuranolone's therapeutic role.