The First Pill For Postpartum Depression Has Been FDA Approved

Any person who has experienced a perinatal mood and anxiety disorder (PMAD) knows the unique challenges of dealing with mental health struggles during pregnancy and the newborn phase. Life is upended overnight. Your body and time are not your own. You thought you were going to feel euphoric and instead, you’re struggling in a way you never have before.

PMADs have historically been both under-researched and underreported, and many people who are affected by PMADs, like postpartum depression (PPD) or postpartum anxiety, are suffering silently, because of inadequate screening, cultural stigma, or lack of access to care. But that is finally beginning to change. As more clinical researchers turn their attention to PMADs, the very real neurological, physiological mechanisms of of these heart-wrenching mental health conditions are finally coming to light. Identifying the cause of PMADS, in turn, has helped destigmatize these conditions and lead to the development of PPD-specific treatments.

Promising research has been done on something called the stress access, also known as the hypothalamic-pituitary-adrenal (HPA) axis. “We’ve had a lot of studies at a high level that have shown that in women who develop clinical depression either in gestation or within the first four weeks of delivery, the stress access is dysfunctional and that neuro-active steroids were not functioning the way they should to manage the stress in the brain,” says Dr. Kristina Deligiannidis, Director of Women’s Behavioral Health at Zucker Hillside Hospital and a professor at the Feinstein Institutes for Medical Research. This lead her to a collaboration with Biogen and Sage Pharmaceuticals to develop a new medication called zuranolone, a neurosteriod aimed directly at treating patients with postpartum depression.

What is zuranolone? The first PPD pill, explained

Zuranolone is an oral neurosteroid, and is the first pill ever to receive FDA approval as a treatment for postpartum depression. Patients are meant to take it at home, and the short, fast-acting 14-day treatment has shown promise in clinical trials. A placebo-control study, published in July of this year in The American Journal of Psychiatry, followed 196 women with postpartum depression for 45 days. While some patients experienced relief after just two doses of the drug, 57% cited significant improvement in their PPD symptoms after 14 days of taking zuranolone. Thirty days after finishing the course, almost 62% of patients who had taken zuranolone were still experiencing significant relief.

Currently, brexanolone — a neurosteriod similar to zuranolone — is the only PPD-specific treatment that is available, but it is an infusion that must be given intravenously over the course of a 60-hours and requires a hospital stay. Time away from family, as well as cost, have meant that it has not been widely used. The hope is that the approval of zuranolone will both help to reduce stigma surrounding postpartum depression, and to fill a gap in care for women with PPD, says Deligiannidis. “There are many gaps right now. We’re not diagnosing it in enough women. We’re not connecting them to care. Many of the standard-of-care antidepressants and psychotherapies, while effective, take time,” she notes.

How is zuranolone different from other antidepressant treatments for PPD?

Researchers like Deligiannidis have known for a long time that neuroactive steroids are really important in the stress management mechanisms of the brain. Women who develop depressive episodes in pregnancy are after delivery are believed to fall into two subtypes: One group is responding to a time when the hormones are high (pregnancy) and the other is responding to crashing hormones (postpartum). The through line is that during the entire perinatal period — that is, the time during pregnancy and following delivery — the brain is making a lot of changes. And, in women with PPD, something is “just sort of disconnecting, and not working as it should,” Deligiannidis explains. “We think it’s the interaction of these really protective neuroactive steroids and the way that they’re functioning in the brain that’s going off course. It tends to happen when women are stressed during periods of these changing hormones.” It is this hypothesis led to the development of both brexanolone and zuranolone.

Zuranolone is different from selective serotonin reuptake inhibitors (SSRIs) like Prozac and Zoloft, which have long been a standard treatment for postpartum-onset depression or anxiety. Unlike an SSRI, zuranolone does not need to be tapered up or down. “It’s meant as an acute treatment course,” Deligiannidis explains. “It allows us to have a fast-acting pill, and get women better, much faster than what we have to date.” (She notes that for patients with more complex psychiatric history, zuranolone may be able to rapidly reduce depression, but they still may have other symptoms they need help with. “So psychotherapies will still be needed, and perhaps even serotonergic antidepressants for longer term treatment of those other issues.”)

When will zuranolone be available?

Zuranolone recieved relatively rapid approval from the FDA because it was given “Priority Review,” meaning that they considered the drug to be groundbreaking and worthy of a fast-tracked review process. However, it’s hard to say exactly when zuranolone will actually become available to people with postpartum depression. It’s possible that the FDA could request more studies, or, they could go right into the labeling process, Deligiannidis says. There is also the question of how quickly the pharmaceutical company can produce the product, and so it’s difficult to know exactly when to expect this treatment to be within reach of people experiencing postpartum depression.

Will people with PPD be able to take zuranolone while breastfeeding?

Whether or not the FDA will consider zuranolone safe to take while breastfeeding remains to be seen. In the study released in July of this year, women were asked to either pump and dump during the 14 days that they were taking zuranolone, or were asked simply not to give their milk to their infant during the treatment course. However, Deligiannidis also did a separate study focused on lactating women and the drug, and found that zuranolone was not passed into the women’s breast milk in a notably high amount. “Actually, it’s much lower amount than the current serotonergic antidepressants. I think that's promising,” Deligiannidis says, adding the caveat that the FDA will ultimately give guidance around questions of the safety of breastfeeding while taking zuranolone, so it is still unclear what the exact recommendations will be.

The bottom line? Postpartum depression is very real.

As a reproductive psychiatrist who has specialized in perinatal care for more than 15 years, Deligiannidis is passionate about identifying the causes of PMADs and developing better treatments, as well as connecting more women with support and care. “I want to encourage women to talk about emotional and behavioral health during pregnancy and postpartum, and to know that this is a real thing,” Deligiannidis says. “Postpartum depression is a medical condition that affects one in eight women approximately in the United States. Right now, according to some data, only about 10% of postpartum women are receiving what we consider adequate treatment, either with psychotherapy or antidepressants. That’s got to change.”

Together with her colleagues in the field of perinatal mental health care, Deligiannidis calls for better screening for PMADs, better diagnosis, and better access to mental health clinicians that know how to care for people who are in the perinatal period, which comes with such unique circumstances and challenges. Zuranolone is one small step in the right direction, and hopefully more treatment options continue to emerge as perinatal mental health care is taken increasingly seriously — as it always should have been.

Studies cited:

Deligiannidis, K., Meltzer-Brody, S., Maximos, B., (2023) Zuranolone for the Treatment of Postpartum Depression. The American Journal of Psychiatry, https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.20220785

Menke, A., (2019) Is the HPA Axis as Target for Depression Outdated, or Is There a New Hope? Frontiers in Psychiatry, https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00101/full

Deligiannidis, K., Meltzer-Brody, S., Effect of Zuranolone vs Placebo in Postpartum Depression. JAMA Psychiatry, https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2781385

Expert:

Dr. Kristina Deligiannidis, M.D., Director of Women’s Behavioral Health at Zucker Hillside Hospital and Professor of Psychiatry, Molecular Medicine and Obstetrics & Gynecology at the Feinstein Institutes for Medical Research.