Experts Highlight Benefits and Offer Caveats for First Postpartum Depression Pill

Damian McNamara, MA

August 09, 2023

For the first time, the US Food and Drug Administration approved a pill taken once daily for 14 days to help women manage the often strong, sometimes overpowering symptoms of postpartum depression.

Medscape Medical News asked several experts in mental health and women's health for their view of this new treatment option for a condition that affects an estimated 1 in 8 women in the United States. What will it mean for easing symptoms like hopelessness, crankiness, and lack of interest in bonding with the baby — and in some cases, thoughts of death or suicide?

A Fast-Acting Option

"We don't have many oral medications that are fast-acting antidepressants, so this is incredibly exciting," said Sarah Oreck, MD, a psychiatrist in private practice in Los Angeles who specializes in reproductive psychiatry. The rapid response is likely because the medication targets the hormonal mechanism underlying postpartum depression, she added.

Zuranolone (Zurzuvae, Biogen/Sage) is different from most other antidepressants — it is designed to be taken for a shorter period. Also, Because zuranolone is a pill, it is more convenient to take than the other FDA-approved treatment, the IV infusion brexanolone (Zulresso, Sage).

"It's obviously game changing to have something in pill form. The infusion has to be done at an infusion center to monitor people for any complications," said Kimberly Yonkers, MD, a psychiatrist specializing in women's health, a Distinguished Life Fellow of the American Psychiatric Association (APA), and the Katz Family Chair of Psychiatry at the University of Massachusetts Chan Medical School/UMass Memorial Medical Center in Worcester.

Women may experience improvement in postpartum depression in as soon as 3 days after starting the medication. In contrast, "typical antidepressants can take up to 2 weeks before patients notice a difference and 4 to 8 weeks to see a full response. A fast-acting pill that can be taken orally could be an ideal option for the 15% to 20% of women who experience postpartum depression," Priya Gopalan, MD, a psychiatrist with UPMC Western Psychiatric Hospital and Magee-Womens Hospital in Pittsburgh, Pennsylvania, said.

The medical community, and reproductive psychiatrists in particular, has always suspected differences in the biological underpinnings of postpartum depression and major depressive disorder, Oreck said. "We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression," she said.

Although selective serotonin reuptake inhibitors (SSRIs) are helpful and currently the standard of care for treating moderate to severe postpartum depression in combination with therapy, Oreck added, early studies suggest that zuranolone may work faster and potentially be more effective than SSRIs in treating the condition.

Zuranolone is a version of a naturally occurring hormone called allopregnanolone, a metabolite of progesterone. Concentrations of allopregnanolone rise dramatically during pregnancy and then drop precipitously after childbirth. Zuranolone works through modulating GABA-A, a neurotransmitter implicated in the development of depression.

"It is encouraging that postpartum individuals may now have more options to manage a debilitating condition that affects them and their families," said Christopher Zahn, MD, interim CEO and chief of clinical practice and health equity and quality for the American College of Obstetricians and Gynecologists (ACOG).

ACOG recommends women be screened for depression at least three times — during early pregnancy, later in pregnancy, and again after delivery. A decision to start this or any other medicine should be individualized and based on shared decision-making between a patient and doctor, Zahn added.

The cost of zuranolone is not yet known. Yonkers said cost of the infusion can serve as a cautionary tale for the manufacturer. Some reports put the infusion cost at $34,000. "Cost is going to be an important component to this. The previous intervention was priced so high that it was not affordable to many people and it was difficult to access."

Beyond "Baby Blues"

The APA has changed the name from "postpartum depression" to "peripartum depression" because evidence suggests feelings and symptoms also can start late in pregnancy. "It means you don't have to wait until somebody delivers to screen for depression. We have to recognize that depression can occur during pregnancy," Yonkers said. "In fact it is not uncommon during the third trimester."

No matter when it starts, the condition can be "very serious," particularly if the person already experiences depression, including bipolar disorder, Yonkers added.

We know that postpartum depression looks different from major depressive disorder and that hormonal shifts during pregnancy and postpartum are a huge risk factor for postpartum depression. Dr Sarah Oreck

Postpartum depression "is more than just 'baby blues.' It is a potentially debilitating illness that causes feelings of intense sadness and worthlessness, making it difficult to care for and bond with your newborn," Gopalan said.

Feelings of exhaustion and frustration are normal with a newborn, but when you start to have difficulty with day-to-day functioning, see yourself withdrawing from life and loved ones, or have thoughts of harming yourself or your baby, these are symptoms of postpartum depression.

Can Be a Medical Emergency

Severe postpartum depression requires immediate attention and treatment. "Any thoughts to harm yourself or others is a psychiatric emergency and care should be sought out in an emergency setting as quickly as possible," Gopalan said. Also, call 988 to connect to your local suicide prevention and crisis hotline if you are having thoughts of harming yourself or your baby.

Yonkers agreed. "One of the things we have to be cautious about is for people with previous predisposition to hurt themselves," she said. "It is therefore important to consider somebody's medical and behavioral health history as well.

"For an individual with recurring depression or severe episodes of depression, this may not be sufficient, because they are just going to get these 14 days of therapy," Yonkers said. "They may need ongoing antidepressants.

"It may not be the right pill for everybody," Yonkers added. She recommended everyone be followed closely during and after treatment "to make sure they are responding and to monitor for relapse."

The Science That Led to Approval

The clinical trials showed early response in patients with severe postpartum depression. Researchers conducted two studies of women who developed a major depressive episode in the third trimester of pregnancy or within 4 weeks of delivery. They found women who took zuranolone once in the evening for 14 days "showed significantly more improvement in their symptoms compared to those in the placebo group."

The antidepressant effect lasted at least 4 weeks after stopping the medication.

Drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection were the most common side effects. The label has a boxed warning noting that the medication can affect a person's ability to drive and perform other potentially hazardous activities. Use of zuranolone may also cause suicidal thoughts and behavior, according to an FDA news release announcing the approval.

The Start of More Help for Mothers?

Zuranolone is not a cure-all. As with most psychiatric prescriptions, the medication likely will work best in conjunction with behavioral health treatments such as psychotherapy, use of other medications, behavioral management, support groups, and self-care tools such as meditation, exercise, and yoga, Gopalan said.

Oreck said she hopes this first pill approval will lead to more discoveries. "I hope this is the beginning of more innovation and development of novel treatments that can target women's mental health issues specifically — female reproductive hormones impact mental health in unique ways and it's exciting to finally see research and development dollars dedicated to them," she said. "The FDA approval of this pill provides the potential to improve the lives of millions of Americans suffering from postpartum depression."

Oreck, Yonkers, Gopalan, and Zahn have disclosed no relevant financial relationships.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care. Follow Damian on Twitter: @MedReporter.

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