The Newly Approved Treatment for Postpartum Depression

Last Friday marked a milestone for maternal health with the FDA’s approval of zuranole (brand name Zurzuvae). Developed by Sage Therapeutics and Biogen, Zurzuvae became the first oral medication approved for postpartum depression (PPD), with an expected launch in the fourth quarter of this year. By improving depressive symptoms within just two weeks of administration, Zurzuvae is poised to provide life-changing care for the thousands of women affected by PPD each year. Even more consequentially perhaps, the approval of Zurzuvae is likely to encourage more women to identify and seek treatment for a condition otherwise plagued by stigma, isolation, and feelings of guilt, shame, and hopelessness.

An estimated 13% of women in the US experience PPD symptoms within a year after giving birth (1). Although each case is unique, women with PPD may experience feelings of anger or irritability, frequent crying, loss of interest, disconnection from their baby, withdrawal from loved ones, intensive worry, and even thoughts of harming themselves or their baby. A myriad of personal and systemic barriers to identification and treatment—from fear of being a “bad mother,” to misconceptions that PPD symptoms are just “normal new mom stuff,” to inadequate screenings—contribute to the estimation that nearly 50% of mothers with PPD are not being diagnosed by their healthcare provider (2). Yet, high overall success rates for PPD treatment, including therapy and medication, paint a hopeful picture for a future in which PPD is increasingly recognized and cared for among new mothers. PPD belongs to a wider category of perinatal mental health (PMH) disorders which, affecting women from pregnancy through a year postpartum, constitute the most common complication of childbearing in the US (3).

While the specific cause of PPD is unknown, evidence has suggested that it may be triggered by the sudden hormonal changes that occur after giving birth, including a significant drop in estrogen and progesterone levels. Zurzuvae contains a synthetic version of allopregnanolone, a neuroactive steroid GABA-A receptor positive allosteric modulator. Though not fully understood, the drug is thought to work by amplifying the activity of GABA-A receptors involved in regulating mood. Notably, levels of allopregnanolone rise during pregnancy but then drop sharply after giving birth. By giving allopregnanolone levels a “boost” postpartum, Zurzuvae may support GABA-A receptor function.

Administered orally once daily for a total of two weeks, Zurzuvae provides a drastically easier and quicker option for women with PPD compared to existing medications. Entering the market as the second-approved PPD drug, Zurzuvae was preceded by brexanolone (brand name Zulresso), which was approved for PPD in 2019. Likewise developed by Sage, Zulresso carries significant drawbacks that have limited its uptake, including requiring a 60-hour IV infusion, carrying risks of loss of consciousness, and costing a steep $34,000. Rather, most women receiving medication for PPD are prescribed a traditional antidepressant, like Serotonin Reuptake Inhibitors (SSRIs). Though providing relief for many women, these drugs take several months to become effective while Zurzuvae can improve symptoms as soon as three days after the initial dose.

Zurzuvae is poised to transform recognition of and treatment for the many mothers suffering from PPD. With the price yet to be announced, however, critical questions regarding insurance coverage and access remain unanswered. In Sage’s recent investor update, the company highlighted planned, but unspecified, efforts to “support our goal that every woman with PPD who is prescribed Zurzuvae can access it, regardless of financial circumstances.” Given the relative failure of its expensive predecessor, legislation supporting coverage for maternity care, and the pervasiveness of PPD, we’re optimistic that Zurzuvae will prioritize accessibility and pave a path towards treatment for women with PPD everywhere.

Sources

1. Depression Among Women | CDC

2. Postpartum Depression Statistics | Recent Research and Data About PPD

3. Depression During Pregnancy & Postpartum | Postpartum Support International (PSI)

4. FDA Approves First Pill for Postpartum Depression - The New York Times (nytimes.com)

5. 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 | Business Wire

6. Zurzuvae (zuranolone) Uses, Dosage, Side Effects, Warnings - Drugs.com

7. PowerPoint Presentation (sagerx.com)