Zuranolone Offers New Hope for Postpartum Depression

In August 2023, the FDA granted approval to zuranolone (Zurzuvae; Sage Therapeutics, Biogen) 50 mg capsules for the treatment of postpartum depression (PPD) in adults. This marks the first-ever oral therapy specifically approved for PPD, shifting the treatment landscape for this high-risk population.¹^,²

PPD is a major depressive episode with onset during pregnancy (third trimester) or within 4 weeks of delivery. It affects approximately 1 in 7 new mothers.³ Untreated PPD can lead to impaired maternal-infant bonding, longer-term depression, and increased risk of suicidal behavior, having a major impact not only on the parent but on the newborn as well.³

Previous treatment options included standard antidepressants (selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) plus psychotherapy, and the only medication specifically approved for PPD was brexanolone (Zulresso; Sage Therapeutics).

Zuranolone is a synthetic neuroactive steroid and a positive allosteric modulator of the gamma-aminobutyric acid (GABA-A) receptor complex.⁴^,⁵ By enhancing inhibitory GABAergic transmission, it is thought to ameliorate dysregulated neural circuits in PPD that may involve hormonal shifts, stress response, and altered GABA activity.⁴^,⁵ Because it is orally bioavailable, zuranolone offers practical advantages over the intravenous-only brexanolone.⁴

Approval of zuranolone was supported by 2 pivotal phase 3 randomized, double-blind, placebo-controlled trials, the SKYLARK (NCT04442503) and ROBIN (NCT02978326) studies, which enrolled adult women whose depressive symptoms began in the third trimester or within 4 weeks of delivery.¹ In the SKYLARK study, patients received 50 mg once daily in the evening for 14 days. Significant symptom improvement (measured by the 17-item Hamilton Rating Scale for Depression [HAMD-17]) was observed on Day 15 vs placebo, and even as early as Day 3.¹^,⁵ The effect was maintained through Day 45 (approximately 4 weeks after dosing ended).⁵ The rapid onset (within days) and short course (14 days) distinguish it from typical antidepressants, which can take weeks to work.³^,⁴

Although the approval covers PPD, the FDA issued a Complete Response Letter for zuranolone’s new drug application for major depressive disorder (MDD), citing insufficient evidence of effectiveness.²

The FDA-approved regimen for this medication is a 50 mg oral capsule once daily in the evening for 14 consecutive days.¹ It should be taken with food (preferably a fat-containing meal) to improve absorption.⁴ Patients are advised not to drive or engage in hazardous activities for at least 12 hours after each dose due to potential somnolence or central nervous system (CNS) depression.²^,⁵

When it comes to the scheduling of the drug, zuranolone is classified as a Schedule 4 controlled substance.¹ Common adverse events (≥5% and greater than placebo) included somnolence, dizziness, fatigue, diarrhea, nasopharyngitis, and urinary tract infections.¹^,⁵ Some of the important warnings of this drug may include somnolence and impairing the ability to drive or operate machinery.²^,⁵ Those taking zuranolone should also monitor for worsening depression or emergence of suicidal ideation.² Effective contraception is recommended during and for 1 week after treatment with this medication.⁴

Pharmacists play a crucial role in implementing zuranolone therapy effectively and safely in clinical practice. This includes patient selection, screening, and identification of adult women meeting criteria for PPD, and assessment for contraindications (eg, sedation risk, hepatic/renal impairment, breastfeeding considerations).²^,⁵ Patients should be educated on the 14-day course, the importance of adherence, expected rapid onset, and what adverse effects to watch for.³ Patients taking zuranolone should be monitored for CNS depression, sedation, and suicidal ideation.²^,⁴

The FDA approval of zuranolone represents a landmark advancement in PPD treatment, offering the first oral therapy for this condition with rapid onset, a short 14-day course, and outpatient feasibility.¹^,³^,⁵ For pharmacy practice, this highlights the expanding role of pharmacists in perinatal mental health and specialty medication management. As more real-world experience accumulates, pharmacists must remain vigilant about safety, adherence, and access issues, especially for postpartum women.

REFERENCES
1. 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. Biogen. News release. August 4, 2023. Accessed November 26, 2025. https://investors.biogen.com/news-releases/news-release-details/fda-approves-zurzuvaetm-zuranolone-first-and-only-oral-treatment

2. FDA approves first oral treatment for postpartum depression. FDA. News release. August 4, 2023. Accessed November 26, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression

3. MacMillan C. What to know about Zurzuvae, the new pill to treat postpartum depression. Yale Medicine. September 15, 2023. Accessed November 26, 2025. https://www.yalemedicine.org/news/postpartum-depression-pill-zurzuvae-zuranolone

4. Zurzuvae FDA approval history. Drugs.com. August 6, 2023. Accessed November 26, 2025. https://www.drugs.com/history/zurzuvae.html

5. Barnes KN, Vogl CM, Nelson LA. Zuranolone: the first FDA-approved oral treatment option for postpartum depression. Ann Pharmacother. 2024;58(7):728-734. doi:10.1177/10600280231204953