RE104 Offers a Revolutionary Approach to Postpartum Depression

Postpartum depression (PPD) is a debilitating disorder that affects one out of seven women within the first year of childbirth. It can interfere with the ability of a mother to care for her child – and herself. In severe cases, PPD can lead to thoughts of self-harm or harm to others, including their own child.

That’s why companies like Reunion Neuroscience are stepping up to address this critical need.

Who Is Reunion Neuroscience?

Reunion Neuroscience is a clinical-stage, venture-backed biopharmaceutical company developing a proprietary drug molecule, called RE104, which has many properties similar to the classic psychedelic hallucinogen, psilocybin. RE104 acts on specific serotonin receptors within the brain that can have an impact on mood disorders, including depression and anxiety.

And that’s where Reunion Neuroscience comes in, with their new treatment and a mission to relieve postpartum depression.

What is Postpartum Depression?

Most new mothers confess to going through the “baby blues” soon after delivery. It typically manifests as anxiety, mood swings, tearful outbursts, and troubled sleep. But the baby blues appear to be a normal response to the life-changing experience of childbirth. And the motherhood that follows. In most cases, it resolves on its own within a few days or weeks.

However, estimates suggest that anywhere between 10 percent and 15 percent of U.S. mothers endure a more intense, lingering form of baby blues called postpartum (or postnatal) depression. This usually crops up within several weeks of childbirth. But, in some cases, caregivers can pick up on it as soon as pregnancy or as late as the child’s first birthday.

Unfortunately, according to research published in 2023 in the American Journal of Obstetrics and Gynecology, postpartum depression rates have been climbing in recent years. And while researchers still aren’t exactly sure what triggers PPD, they have identified certain risk factors, such as:

• Prior history of mental health difficulties (especially depression and bipolar disorder).
• Little to no social support.
• A difficult pregnancy.
• Recent stressful life events.
• Marital strain.
• Limited healthcare access.

Another disturbing trend reveals that PPD disproportionately affects historically disadvantaged populations, such as single mothers, Black and Hispanic mothers, and those in lower-income homes.

Given PPD’s profound impact, it’s frustrating – if not tragic – to see how few effective treatments have made it to market.

Existing Postpartum Treatments

The earliest treatment involved the off-label use of selective serotonin reuptake inhibitors (SSRIs), often with questionable efficacy.

Then, in 2019, the U.S. Food and Drug Administration (FDA) signed off on an intravenous formulation for postpartum depression called Zulresso (brexanolone). However, most mothers couldn’t get access since treatment demands constant monitoring at a designated facility. Treatment consists of a continuous infusion for 60 hours.

Four years later, in 2023 the FDA approved an oral, once daily, 14-day treatment for PPD called Zurzuvae (zuranolone). 

While existing options have brought hope to some, the limitations in efficacy, convenience, and accessibility underscore an urgent need for more innovative solutions. This gap in care illustrates why RE104 could represent a turning point in the treatment landscape.

Understanding RE104

RE104 is a best-in-class, fast-follower proprietary molecule that Reunion Neuroscience developed that targets the serotonin 2A receptor, which is responsible for the antidepressant effects of hallucinogens. The molecule is a prodrug of 4OH-DiPT, which resembles psilocybin.

Several key features distinguish RE104 from existing pharmacologic PPD treatments.

First, caregivers administer RE104 as a single-dose IV formulation. It doesn’t require a prolonged hospital stay or round-the-clock surveillance. That makes it more convenient for underserved or time-constrained mothers – as well as the healthcare providers treating them.

The hallucinogenic effects are short-lived: 3.7 hours, compared to psilocybin’s effects, which can last as long as eight hours. But according to Reunion scientists its therapeutic effects last much longer. 

From the results of the phase 1 clinical trial, the side effect profile of RE104 is also more favorable than the existing treatment options, with only mild and relatively short-lived side effects. 

The promising results of the just-completed phase 1 clinical trial have paved the way for the phase 2 RECONNECT trial, a multi-center, randomized, double-masked, parallel-group, active dose-controlled clinical trial of RE104 recruiting mothers with PPD, which launched earlier this year.

If you or someone you know is experiencing postpartum depression and may be interested in participating in the RECONNECT trial, you can find more information about eligibility and enrollment here. This is an opportunity to be part of research that could change the world of maternal mental health treatment. 

The Reunion execs say the study should wrap up in mid-2025. The team at Reunion remains in constant contact with FDA officials about the possibility of earning “special drug” status if the latest round of trials are favorable.

The pharmaceutical company has also teamed up with several groups to raise awareness about postpartum depression and maternal mental health. This includes partnerships with the Seleni Institute and the “Is Mom OK?” initiative from Cherished Mom. Other partnership opportunities are in the pipeline.

Through these collaborations and clinical advancements, Reunion Neuroscience is not just developing a drug – it is championing a movement to transform maternal mental health.

Bottom Line

Reunion Neuroscience’s RE104 offers a groundbreaking approach to treating postpartum depression, addressing a critical gap in maternal mental health care. With its convenient formulation, shorter duration of effects, favorable side effect profile, and promising therapeutic outcomes, this novel treatment could bring relief to countless mothers navigating the challenges of PPD.

Researchers are also exploring RE104 as a possible treatment for adjustment disorder, another yawning gap in the mental health community.

RECONNECT is not just a clinical trial – it’s a journey to reconnect mothers with their babies, their families, and themselves, bringing hope and healing to those who need it most.

Further Reading

• Rates of Major Depressive Disorder and Bipolar Disorder in Black and White Postpartum Women
• Public Health Nurse-Delivered Group CBT for PPD
• Effect of Zuranolone on Anxiety and Insomnia in Postpartum Depression