Interim study finds sustained postpartum depression improvement through Day 45 with oral zuranolone

A phase 4, prospective, real-world study found that zuranolone (Zurzuvae; Sage Therapeutics and Biogen) produced clinically meaningful improvement in postpartum depression (PPD) symptoms by the end of the 14-day treatment course, with reductions sustained roughly 30 days later. Interim results, drawn from patient-reported outcomes across varying baseline severities, were previously presented at the Academy of Managed Care Pharmacy Annual Meeting, in addition to the Postpartum Support International (PSI) meeting in Los Angeles, California, held June 24-28, 2026.

According to the poster authors, led by principal investigator Joy Baker, ob-gyn, PPD affects approximately 13.2% of postpartum individuals and carries consequences for both maternal health and infant well-being. Zuranolone, a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic type A gamma-aminobutyric acid (GABAA) receptors, is the first and only oral treatment approved by the FDA for adults with PPD. Because pivotal phase 3 trials enrolled primarily patients with severe disease, investigators designed this study to evaluate effectiveness across the full severity spectrum, including moderate PPD.

Adults filling an initial zuranolone prescription at a national specialty pharmacy were recruited by email or call center between June 26, 2025, and January 23, 2026. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) at baseline (Day 0), immediately after treatment (Day 15), and at follow-up (Day 45).

Of 202 enrolled participants, 191 completed all 3 surveys, a retention rate of 94.6%. Participants with moderate PPD (EPDS 14 to 19) were oversampled to support subgroup analysis. Clinical symptom remission was defined as an EPDS total score cutoff less than 10, and mean changes were assessed using paired t-tests.

The analyzed cohort had a mean age of 30.9 years. At baseline, 9.9% had mild, 53.4% moderate, and 36.6% severe PPD. Zuranolone served as first-line PPD therapy for 51.8% of participants, and 35.6% received it as their only PPD treatment; concurrent antidepressants (47.1%) and psychotherapy (32.5%) were the most common accompanying therapies.

Symptom reductions across severity groups

Across the full cohort, mean EPDS scores fell by 8.91 points at Day 15 and 10.24 points at Day 45 (both P < 0.001). Improvements were observed across every severity group. Participants with moderate PPD saw mean reductions of 8.59 points at Day 15 and 9.62 points at Day 45, while those with severe PPD saw reductions of 10.89 and 12.04 points, respectively. Mild PPD reductions reached 3.42 points at Day 15 (P = 0.026) and 6.95 points at Day 45.

More than half of all participants met the EPDS remission threshold by Day 15 (55%), rising to 67% by Day 45. Remission was higher among participants with mild (68% to 84%) and moderate (63% to 78%) PPD than among those with severe PPD (41% to 46%).

Breastfeeding and subsequent treatment

Among participants, 46% reported feeding breast milk during treatment, with 41% feeding as usual and 5% feeding less. At Day 45, 71% did not report starting a new type or class of PPD treatment; 49% required no additional treatment beyond zuranolone, and 22% continued the same concurrent therapy used at baseline.

The authors noted limitations including potential recall and selection bias and reporting that was not verified against claims or electronic medical record data. Symptom improvement in the moderate PPD subgroup, a population underrepresented in earlier registration trials, extends the real-world evidence base for oral zuranolone.

“Regardless of baseline PPD severity, participants treated with zuranolone experienced clinically meaningful symptom improvement by end of treatment (Day 15) that was maintained through Day 45,” the authors wrote. “Future surveys should explore reasons surrounding breastfeeding decisions during treatment.”

Reference:

1. Baker LJ, Nagle-Yang S, Bian B, et al. Real-world effectiveness of zuranolone in postpartum depression: interim results of a prospective observational study. Poster. Presented at: Postpartum Support International meeting. June 24-28, 2026. Los Angeles, California.