Zuranolone Approved as First, Only Oral Medication to Treat Postpartum Depression

The FDA has approved zuranolone (Zurzuvae) as the first oral medication indicated for the treatment of postpartum depression (PPD) in adults, representing a new treatment option for those living with PPD. Previously, PPD treatment was available only as an intravenous injection, administered by a health care provider.

PPD is a major depressive episode typically experienced after childbirth, although it can begin during the late stages of pregnancy. The condition is characterized by sadness, a loss of interest in activities previously enjoyed, and a decreased ability to feel pleasure, and presents with symptoms that may include cognitive impairment, feelings of sadness or inadequacy, loss of energy, and/or suicidal ideation. It is estimated that 1 in 8 women in the United States experiences symptoms of PPD, yet only 15.8% of women with PPD symptoms receive treatment.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness—even, in severe cases, thoughts of harming themselves or their child,” said Tiffany R. Farchione, MD, director of the division of psychiatry at the FDA Center for Drug Evaluation and Research. “And because [PPD] can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development.”

“Having access to an oral medication will be a beneficial option for many of those women coping with extreme, and sometimes life-threatening, feelings,” she continued.

Zuranolone efficacy was demonstrated through the NEST clinical development program, which included 2 randomized, double-blind, placebo-controlled, multicenter studies; participants included women with PPD who met the Diagnostic and Statistical Manual of Mental Disorders criteria for a major depressive episode, whose symptoms began in either the third trimester of pregnancy or within 4 weeks of delivery.

In the first study (NCT04442503), patients received zuranolone 50 mg or placebo for 14 days, once daily in the evening. In the second study (NCT02978326), patience received another zuranolone product, equal to 40 mg zuranolone or placebo—over a 14-day period. Patients were monitored for 4 weeks after the conclusion of the 14-day treatment period. The primary endpoint of these studies was the change in depressive symptoms, determined via the total score from the 17-item Hamilton depression rating scale (HAMD-17), measured at day 15.

Across both studies, women in the zuranolone groups demonstrated significantly more symptom improvement vs placebo. This treatment effect was maintained at day 42, or 4 weeks after the last zuranolone dose.

The approval “marks a groundbreaking day for the treatment of PPD, as…we now have an oral treatment option that can provide rapid improvements in depressive symptoms in as early as three days for women with PPD,” said Kristina Deligiannidis, MD, professor at The Feinstein Institutes for Medical Research in Manhasset, New York, and a principal investigator in the zuranolone clinical development program. “As a perinatal psychiatrist, I see the devastating impact PPD has on mothers, particularly on the important mother-infant bond and long-term child development.”

Zuranolone includes a boxed warning that the medication can impact a person’s ability to drive and perform other potentially hazardous activities; patients may not be able to assess their degree of impairment. Common side effects include drowsiness, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection.

It is expected that zuranolone will be available in the fourth quarter of 2023. The DEA is anticipated to schedule the medication as a controlled substance with in 90 days.

References

1. FDA approves first oral treatment for postpartum depression. News release. FDA. August 4, 2023. Accessed August 8, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

2. FDA approves Zurzuvae (zuranolone), the first and only oral treatment approved for women with postpartum depression, and issues a complete response letter for major depressive disorder. News release. Biogen. August 4, 2023. Accessed August 8, 2023. https://investors.biogen.com/news-releases/news-release-details/fda-approves-zurzuvaetm-zuranolone-first-and-only-oral-treatment