New drug zuranolone targets postpartum depression in women

Zuranolone is the first oral drug approved by the FDA specifically to treat the severe depression that persists in large numbers of new mothers well after they give birth.
Oct. 26, 2023
Mother with her under one-year-old child. Zuranolone is the first oral drug approved by the FDA specifically to treat the severe depression that persists in large numbers of new mothers well after they give birth.
Zuranolone is the first oral drug approved by the FDA specifically to treat the severe depression that persists in large numbers of new mothers well after they give birth. Photo: Getty Images.

In early August, the Food and Drug Administration (FDA) announced approval of a new drug to treat postpartum depression in adult women. Zuranolone (brand name Zurzuvae) became only the second drug specifically approved to treat postpartum depression, and the first that women can take orally.

If zuranolone can help to curb the many debilitating symptoms of postpartum depression, including mental suffering and sometimes death, it will be a great boon for the roughly one in seven women who cope with postpartum depression. But the benefits of improving a mother’s mental health go even further, said Dr. Sarah Nagle-Yang, associate professor at the University of Colorado School of Medicine’s Department of Psychiatry. Nagle-Yang treats patients in the department’s Women’s Behavioral Health and Wellness Service.

Dr. Sarah Nagle-Yang treats postpartum depression and mental health issues at the University of Colorado’s Women’s Behavioral Health and Wellness Service. Photo by the University of Colorado School of Medicine.
Dr. Sarah Nagle-Yang treats postpartum depression and mental health issues at the University of Colorado’s Women’s Behavioral Health and Wellness Service. Photo by the University of Colorado School of Medicine.

“We know that having a healthy mom is what is really good for babies,” said Nagle-Yang. “That means [maintaining the mother’s] physical and mental health.”

The approval of zuranolone could also be important if it draws more attention to the broader need for maternal mental health services, not as a separate entity, but as an integral part of their overall care, said Dr. M. Camille Hoffman, professor of Maternal Fetal Medicine in the University of Colorado School of Medicine departments of Obstetrics & Gynecology and Psychiatry.

“The concept is really that your mental health and your body are not separate,” Hoffman said.

UCHealth Today spoke with Drs. Nagle-Yang and Hoffman about the details of the zuranolone approval and its place in the treatment of postpartum depression and maternal mental health.

What is postpartum depression?

The Diagnostic and Statistical Manual of Mental Disorders (DSM–5) defines it as a “major depressive episode,” diagnosed by the finding of at least five of nine specific symptoms that last at least two weeks after childbirth. Among these are persistent depression, loss of energy, insomnia, and feelings of worthlessness. The length of the postpartum period varies among professional entities, Hoffman said, but she added that “most of our messaging in [obstetrics and gynecology] is we should consider [it] the first year after a pregnancy.”

Is postpartum depression different than ‘baby blues’?

Yes. Baby blues, or postpartum blues, involve short-term feelings of sadness and mood swings that are common for women after giving birth. Postpartum depression lasts much longer and with more severe symptoms.

“Postpartum blues really shouldn’t persist beyond 14 days,” Hoffman said. “If somebody is hyperemotional, feeling down, feeling hopeless, any of the things that can also characterize postpartum depression, and they are three months out, we should not call that post-birth blues anymore.”

How serious a risk to mothers’ health is postpartum depression?

Very serious. “As it relates to maternal morbidity and mortality, it’s one of the leading causes,” Hoffman said. She noted that suicide and accidental drug overdose are the top two reasons that mothers die in the first postpartum year.

Maternal fetal medicine specialist Dr. M. Camille Hoffman says postpartum depression is a major health risk for new mothers. Photo by the University of Colorado School of Medicine.
Maternal-fetal medicine specialist Dr. M. Camille Hoffman says postpartum depression is a major health risk for new mothers. Photo by the University of Colorado School of Medicine.

Explain the importance of zuranolone for the treatment of postpartum depression

Zuranolone is the first oral medication approved by the FDA specifically to treat postpartum depression in adult women. Hoffman calls it “a step forward” in treating the condition.

“It acts rapidly, reduces depressive symptoms compared to placebo, and a course [of the medication] is only 14 days with results that are sustained out to at least 45 days,” she said.

Does zuranolone have other advantages over current treatments for postpartum depression?

Yes. Hoffman and Nagle-Yang both emphasized that the new drug acts more quickly and in a shorter time than other medications used to treat postpartum depression. That is very important for mothers dealing not only with mental health challenges but also the stress of caring for a new baby and everyday challenges, Nagle-Yang said.

“We know that postpartum depression has well-established negative outcomes, and every day in the postpartum period counts,” she said.

“During the postpartum period, when infants are changing rapidly, this is an even more critical period to improve maternal mental health and get symptoms under control,” Hoffman added.

How does zuranolone work?

In very simplified terms, Zuranolone aims for receptors in the brain that help to manage mood and stress. These receptors depend on allopregnanolone, a steroid that those receptors rely on to do their mood-regulating job. However, levels of allopregnanolone can become depleted in women with postpartum depression. Zuranolone plays the steroid’s role and helps to restore regulatory balance in the brain relatively quickly.

Are there any other drugs that specifically treat postpartum depression?

Yes. Brexanolone (brand name Zulresso) was the first FDA-approved treatment specifically for postpartum depression. Brexanolone works in the same way as zuranolone to treat the condition, but it is delivered through a 60- to 72-hour IV infusion that requires continuous monitoring. “The logistics of administering [brexanolone] has been a major barrier,” Nagle-Yang said.

Are there other drug treatment options for postpartum depression?

Yes. Antidepressant medications, such as selective serotonin reuptake inhibitors, or SSRIs, are important “first-line treatments” for symptoms of postpartum depression and other mood disorders, Nagle-Yang said. However, SSRIs and other antidepressants act broadly, while “Zuranolone is one of the first examples of a medication that has a more specific target on causing postpartum depression,” she said.

Nagle-Yang emphasized that while SSRIs, such as sertraline and escitalopram, are not approved specifically to treat postpartum depression, they can be effective “and are truly lifesaving options for many,” she said.

Hoffman also noted that these other medications can help women manage depression during their pregnancy. That is key because depression during pregnancy – or before – is a significant risk factor for postpartum depression. For that reason, Hoffman said, pregnant women should receive treatment for their depression, including medications and therapy, just as they do for diabetes and hypertension, which also pose serious risks to themselves and their babies.

Nagle-Yang added that Zuranolone will not be a substitute for other antidepressants, talk therapy or other treatment options for postpartum depression. “This medication will not be for everyone, and we will be learning more about how it can be most effectively used with time,” she said.

Can zuranolone be taken with other antidepressant medications?

Yes. A practice advisory issued by The American College of Obstetricians and Gynecologists (ACOG), which Hoffman helped to develop, states that “Zuranolone can be used alone or as an adjunct to other oral antidepressant therapy like SSRIs and SNRIs” (serotonin-norepinephrine reuptake inhibitors).

Are there side effects or risks in taking zuranolone?

The ACOG advisory lists a number of side effects, including dizziness, fatigue, and urinary tract infections.

Does zuranolone affect breast milk and breastfeeding?

That is not yet clear. The ACOG advisory also notes that zuranolone passes into breast milk but adds there are not yet data on whether or not it affects breastfed infants or the amount of milk breastfeeding mothers produce.

When will zuranolone be available?

That has not yet been announced. The drug developers Biogen and Sage Therapeutics have put the launch date sometime in the fourth quarter of 2023.

Why don’t we know the cost of zuranolone?

One complicating factor, Hoffman said, is that the drug did not receive FDA approval to treat major depressive disorder, one of the most common mental health problems worldwide, as the developers had hoped. That will mean “a much smaller proportion of eligible recipients,” Hoffman explained.

Are there risk factors for postpartum depression?

Yes. There are many, including changes in hormone levels. Some of them overlap with risk factors for depression generally, Nagle-Yang said. As mentioned earlier, depression during pregnancy increases the risk for postpartum depression. People who have a history of depression, anxiety and mood disorders before they are pregnant are also “at fairly high risk,” Nagle-Yang said, as are those with family histories of perinatal or postpartum depression, “even if they have not had a personal history” of the problem. People with other mental health disorders, such as obsessive-compulsive disorder, are at higher risk, she added.

Stress is also a significant risk factor for postpartum depression. Those pressures can be caused by financial problems or by “microaggressions, discrimination and social and psychosocial sources,” Nagle-Yang said. She also cited pregnancy loss, high-risk pregnancies, the birth of a child with complex medical needs, and traumatic deliveries as factors that can lead to postpartum depression.

“Even something that from a medical provider’s standpoint feels low risk, sometimes people can experience as traumatic or that their life was threatened,” Nagle-Yang said.

More generally, individuals and society may have “unrealistic expectations” for what a new mother can handle during the vulnerable postpartum period, Nagle-Yang said. The simultaneous responsibilities can include maintaining a breastfeeding schedule, taking care of other kids, and going back to work.

“Thinking about how people who surround a postpartum individual can logistically and practically support families is really important,” in lightening the burden and decreasing the risk of postpartum depression, she said.

Can the risk of postpartum depression be mitigated with drug treatment during pregnancy?

Yes. As mentioned, medications such as SSRIs are effective treatments for depression and can help to reduce the risk of postpartum depression. The key is early diagnosis through screening and developing a treatment plan, Hoffman said. It’s sometimes necessary, she added, to overcome the fear that medications will hurt the baby, as well as the stigma that is still attached to treating mental health disorders. That is in spite of the fact that studies have demonstrated generally the safety of taking antidepressants during pregnancy, she added.

“One of the points I try to make with patients is, ‘Taking these [drugs] are safer than you just limping along or struggling with depression throughout your pregnancy. These are the known risks of untreated depression and anxiety for both mother and baby. These [medications] are how we treat them.’”

Can the treatments also include mental health therapy?

Yes. Women can receive treatments like cognitive behavioral and interpersonal therapy adapted for perinatal needs. Those services and many others are available from the interdisciplinary team at the Women’s Behavioral Health and Wellness Service, which Nagle-Yang helps to lead.

“I see people who have depression during pregnancy commonly,” Nagle-Yang said. The goal, she said, is to provide those individuals with supportive therapies and medications to help them achieve remission of their depression and be “well-positioned to go into the postpartum period and reduce the risk of recurrence [of their depression].”

Hoffman also pointed to care for perinatal mood disorders provided through the PROMISE Clinic of the University of Colorado Obstetrics & Gynecology (OB-GYN) practice. The clinic integrates psychiatric and OB-GYN care, including screenings, treatments and community referrals, for women from roughly the halfway point of their pregnancy through the first month postpartum.

Nagle-Yang said that the PROMISE Clinic’s integrated care team model can be “the most straightforward and evidence-based way” to help pregnant women overcome the stigma of acknowledging and treating mental health challenges.

“We have those resources on the Anschutz Medical Campus,” Nagle-Yang said. “These models can be and should be expanded so that any obstetrics practice can have an integrated mental health plan.”

Are there other steps being taken to help provide mental health services for pregnant women in Colorado?

Yes. Nagle-Yang and Hoffman stated that the Department of Psychiatry at the University of Colorado has received a grant from the federal Health Resources & Services Administration (HRSA) to build a Perinatal Psychiatry Access Program. These programs, which are thus far funded with five-year grants in seven states, aim to increase the capacity for delivering mental health services to perinatal women and thus decrease the risk of postpartum depression. Nagle-Yang said Dr. Celeste St. John Larkin, assistant professor in the Department of Psychiatry, will lead the efforts to build the program, which is still in its very early stages.

I want to understand more about postpartum depression and other maternal mental health issues. What are some useful resources?

Hoffman singled out the National Child & Maternal Mental Health Education Program and Postpartum Support International. UCHealth also offers resources on subjects that include maintaining a healthy mood during pregnancy and obtaining postpartum nursing support.

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.