Postpartum depression (PPD) is a serious, often devastating mood disorder that can affect new mothers after childbirth. For years, treatment options were limited to traditional antidepressants, which can take weeks to work, and psychotherapy.
In 2019, the approval of brexanolone (marketed as Zulresso) by the U.S. Food and Drug Administration (FDA) was hailed as a breakthrough — the first drug specifically approved to treat PPD. Yet, as of January 1, 2025, Zulresso is no longer commercially available in the United States.
So what happened? Let’s take a closer look at why this promising treatment didn’t remain a mainstay — and what new options have emerged.
What Was Zulresso?
Zulresso’s active ingredient, brexanolone, is a synthetic version of allopregnanolone, a hormone naturally produced in the body that plays a crucial role in mood regulation. After childbirth, hormonal shifts can cause allopregnanolone levels to plummet, potentially contributing to the onset of PPD.
Brexanolone works by modulating GABA-A receptors in the brain — the same receptors influenced by benzodiazepines, but through a different, more targeted mechanism. Clinical trials showed that Zulresso could significantly reduce depressive symptoms within just 2.5 days of starting treatment (FDA, 2019).
This rapid onset was a major advantage compared to traditional antidepressants, which can take four to six weeks to become effective.
Why Was Zulresso Discontinued?
Despite its potential, Zulresso faced several major challenges that limited its widespread adoption:
1. Intensive Administration Requirements
Zulresso required a continuous 60-hour intravenous (IV) infusion in a certified healthcare facility. New mothers had to stay hospitalized for more than two days — a logistical and emotional hurdle for families with newborns.
Not surprisingly, many women found it difficult (or impossible) to leave their infants for such a long time.
2. Serious Safety Concerns
Due to the risk of excessive sedation and sudden loss of consciousness, Zulresso was subject to a strict Risk Evaluation and Mitigation Strategy (REMS) program (FDA REMS, 2019). Patients needed to be monitored with continuous pulse oximetry and have a caregiver present during interactions with their child.
While necessary for safety, these requirements made the treatment even less accessible.
3. High Costs
The treatment came with a hefty price tag: the drug itself cost around $34,000 — not including hospital fees for the 60-hour stay (The New York Times, 2019). Even with insurance, many families could not afford Zulresso.
4. Emergence of Oral Alternatives
Perhaps the final blow came with the approval of zuranolone (Zurzuvae) in August 2023. Zurzuvae is the first oral medication specifically indicated for postpartum depression (Sage Therapeutics, 2023).
It requires a simple 14-day course of oral pills — a far easier and less invasive treatment compared to a hospital stay and IV infusion. Given its convenience, many physicians and patients began opting for Zurzuvae over Zulresso.
The Future of PPD Treatment
While Zulresso offered a groundbreaking new pathway for treating postpartum depression, its practical limitations ultimately led to its withdrawal from the market.
Today, the future looks brighter. Oral treatments like Zurzuvae offer a more accessible option, and research into faster-acting, hormone-based therapies continues to expand. For the millions of women affected by PPD each year, these developments are a crucial step forward.
If you or someone you know is experiencing symptoms of postpartum depression, talk to a healthcare provider about the latest treatment options. Help is available — and it’s becoming easier to access than ever before.
References:
- U.S. Food and Drug Administration (FDA). FDA Approves First Treatment for Postpartum Depression, 2019.
- The New York Times. A New Drug Offers Hope for Postpartum Depression, March 2019.
- Sage Therapeutics. FDA Approval of Zurzuvae for Postpartum Depression, August 2023.