The First Oral Treatment for Postpartum Depression is Finally Here
As of December 14, 2023, a new medication, Zurzuvae™ (also called zuranolone), is now available for the treatment of postpartum depression following the U.S. Food and Drug Administration’s approval earlier this year.
This marks a huge step forward for women and birthing people experiencing postpartum depression—a mental health condition that impacts at least 1 in 7 mothers.
Zurzuvae is the first and only oral drug specifically designed to treat postpartum depression. It is a once-daily, 14-day treatment that, for some patients, improves symptoms as early as three days into taking the medication.
Experts in the field of maternal mental health note that Zurzuvae could be a game-changer for women experiencing postpartum depression. Kristina Deligiannidis, MD, a principal investigator in the Zurzuvae clinical trials says, “Having an option like Zurzuvae that can work at day 15 and improves symptoms as early as three days has the potential to make a profound difference in the lives of women with postpartum depression.”
With this new pharmaceutical development in the field of maternal mental health, there are many questions being asked by healthcare providers, mothers, and birthing people: How does Zurzuvae work? What are the side effects? How is it different than current antidepressant medications? Will insurance cover Zurzuvae? Is Zurzuvae safe for breastfed babies?
In this article, we aim to answer these questions with the latest information available, and we will continue to provide updates as new developments and answers come forward.
What is Zurzuvae? How does it work?
Zurzuvae (zuranolone) is a synthetic form of allopregnanolone—a naturally occurring metabolite of progesterone.
Although progesterone is present in the body all the time, it increases significantly during pregnancy and then drops precipitously to pre-pregnancy levels in the immediate postpartum period.
Researchers have long thought this dramatic change in progesterone levels has led to postpartum depression in some women.
Allapregnanolone modulates GABA receptors in the brain, which regulate mood and behavior. The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function.
According to Dr. Katrina Furey, a psychiatrist at Yale School of Medicine, “When a woman has postpartum depression, she doesn’t have enough allopregnanolone, and her GABA-A receptors aren’t firing right, which is what makes her irritable, anxious, and depressed.” Dr. Furey says that Zurzuvae helps the GABA-A receptors work a little better, leading to calming, antidepressant properties.
What are the side effects?
According to the Massachusetts General Hospital Center for Women’s Mental Health, Zurzuvae has a “good safety profile” and is “well-tolerated” with the most common adverse events including headache, dizziness, and sedation. Because of the sedation side effect, it is recommended that Zurzuvae be taken in the evening.
How does Zurzuvae differ from traditional antidepressant medications?
Both Zurzuvae and commonly used antidepressant medications (e.g. selective serotonin reuptake inhibitors, also called SSRIs) target neurotransmitters in the brain; however, there are several differences: Zurzuvae targets GABA, is quick acting (results within days), and is used for a short duration (2-week course of treatment). SSRIs target serotonin, take longer to act (usually 4-6 weeks), and often require long-term daily use.
How much does Zurzuvae cost?
The cost of a complete 14-day treatment of Zurzuvae is almost $16,000. However, this is not the price that individual consumers will pay.
Sage Therapeutics and Biogen, the two companies bringing Zurzuvae to market, have stated their goal of broad, affordable access for women with postpartum depression and are working to enable women to access treatment with minimal restrictions and, where possible, with little to no co-pay regardless of financial means.
“Our goal is to…enable broad and equitable access for women with postpartum depression who are prescribed this drug,” says Barry Greene, CEO of Sage Therapeutics.
Sage Therapeutics and Biogen have also launched a patient support program, ZURZUVAE For You, which provides educational resources, help with understanding insurance coverage, and assistance navigating the prescription fulfillment process. The program also includes financial assistance, such as a copay assistance program, and, in some cases, offers the product at no cost for eligible patients.
Does insurance cover Zurzuvae?
The Policy Center for Maternal Mental Health published a report showing that 17 insurance companies and one pharmacy benefit manager (PBM) offer some form of coverage for Zurzuvae. However, the insurers who have published their policies have several limitations surrounding the coverage of Zurzuvae.
It is important to note that lack of coverage in an insurance policy does not mean an insurer will not cover Zurzuvae; prescribers can submit prior authorization requests to learn whether insurance will cover the drug and if any limitations apply.
We will continue to monitor the situation as a lack of insurance coverage can be a significant barrier to accessing this medication. Hopefully over the coming months, more insurance companies will cover Zurzuvae and will consult with experts to ensure that their policies do not pose unnecessary burdens to the patients seeking treatment.
In the meantime, patients who are struggling to cover the cost of Zurzuve can seek help through ZURZUVAE For You, which is a patient support program that provides educational resources, help with understanding insurance coverage, and assistance navigating the prescription fulfillment process. The program also includes financial assistance, and in some cases, offers the product at no cost for eligible patients.
Can women breastfeed while taking Zurzuvae?
Women who participated in the clinical trials for Zurzuvae were required to abstain from breastfeeding or providing breast milk to their infants, so there is very little data about the impact on newborns.
According to the American College of Obstetricians and Gynecologists, Zurzuvae passes into breast milk, although at lower levels than traditional antidepressant medications. There is currently no data on the effects of Zurzuvae on a breastfed infant and limited data on milk production. The patient’s clinical need for Zurzuvae and the developmental and health benefits of breastfeeding should be evaluated through a shared decision-making process that considers continuation, pumping and discarding milk through 1-week past treatment completion, and cessation.
According to the Drugs and Lactation Database (LactMed), published by the National Institute for Biotechnology Information, because of the low amounts of Zurzuvae in breast milk, it would not be expected to cause any adverse effects in breastfed infants. If Zurzuvae is required by the mother, it is not a reason to discontinue breastfeeding. Until more data is available, Zurzuvae should be used with careful infant monitoring for excessive sedation during breastfeeding, especially with higher dosages and in the cases of taking Zurzuvae while breastfeeding newborn and preterm infants.
Why is there so little research on the impact of medications on pregnant and lactating women?
Pregnant and lactating women have long been excluded from clinical trials, rendering them “therapeutic orphans.” In fact, the U.S. Food and Drug Administration has long excluded women of childbearing age from clinical trials for concern about the impact of medication on the fetus or infant. As a result, there is not enough known about the effect of most drugs on a woman, her pregnancy, or her breastfed infant.
The Coalition to Advance Maternal Therapeutics (CAMT) was launched in 2014 to advocate for policy changes and raise awareness of the need for greater inclusion of pregnant and lactating people in clinical research. According to Katie Schubert, CEO of the Society for Women’s Health Research and immediate past Chair of the Maternal Mental Health Leadership Alliance’s Board of Directors, “CAMT is committed to raising awareness among policymakers and the industry about the need to include pregnant and lactating women in clinical research to better understand the safety and efficacy of prescription drugs, therapeutics, and vaccines used during pregnancy and breastfeeding.”
•••
Zurzuvae has the potential to make an incredible difference in the lives of new mothers, birthing people, and their families, and we are grateful to the teams at Sage Therapeutics and Biogen for bringing this drug to market.
However, two important issues must be addressed to ensure easy, appropriate, and equitable access to this groundbreaking treatment: insurance coverage to make Zurzuvae affordable, and more research and official guidance on breastfeeding while taking Zurzuvae.
This medication will be most impactful if (1) people can afford it and (2) parents do not have to choose between supporting their mental health and breastfeeding their baby.
We will be monitoring these issues, looking for policy solutions, and sharing insights and information as more data about Zurzuvae becomes available.
Sources
ACTA Endocrinology, July-September 2019: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992410/#:~:text=Hormonal%20changes%20during%20labour%20and%20postpartum&text=Progesterone%20is%20the%20most%20abundant,allopregnanolone%20seem%20to%20decrease%20irritability
American College of Obstetricians and Gynecologists, August 2023:
Biogen News Release, August 4, 2023:
British Journal of Clinical Pharmacology, February 2018:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777434/
Businesswire, November 7, 2023:
https://www.businesswire.com/news/home/20231107571536/en
Drugs and Lactation Database (LactMed), September 15, 2023:
FDA Announcement, August 4, 2023:
Massachusetts General Hospital Center for Women’s Mental Health, July 28, 2023:
Policy Center for Maternal Mental Health, December 10, 2023:
Sage Therapeutics press release, December 14, 2023:
Society for Women’s Health Research website:
Stat Pearls, May 1, 2023:
https://www.ncbi.nlm.nih.gov/books/NBK554406/
Yale Medicine article, September 15, 2023:
https://www.yalemedicine.org/news/postpartum-depression-pill-zurzuvae-zuranolone
