Justice Delayed: The Case of Zuranolone and Barriers to Advancing Perinatal Mental Health.

Justice Delayed: The Case of Zuranolone and Barriers to Advancing Perinatal Mental Health - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Search Log in Primary site navigation Search Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Psychiatr Serv . Author manuscript; available in PMC: 2026 Jun 5. Published in final edited form as: Psychiatr Serv. 2025 Jun 5;76(8):764–766. doi: 10.1176/appi.ps.20250025 Justice Delayed: The Case of Zuranolone and Barriers to Advancing Perinatal Mental Health Catherine Yang 1 , Emily M Beydler 1 , Manon Lefèvre 2 , Dominic Sisti 1, 2 Author information Article notes Copyright and License information 1 University of Pennsylvania, Department of Psychiatry 2 University of Pennsylvania, Department of Medical Ethics and Health Policy ✉ Correspondence: Catherine Yang, catherine.yang@pennmedicine.upenn.edu , Market St Philadelphia, PA 19104 Issue date 2025 Aug 1. PMC Copyright notice PMCID: PMC12316555  NIHMSID: NIHMS2079381  PMID: 40471055 The publisher's version of this article is available at Psychiatr Serv Abstract By discussing challenges in the development of and access to zuranolone—an innovative oral pharmacological treatment for postpartum depression—this paper examines the systemic exclusion of women’s mental health issues from research and advocacy efforts, highlighting how these gaps perpetuate injustice within the healthcare system. Issues such as inadequate funding for women’s mental health research, insurance coverage limitations, and inequities in treatment accessibility represent systemic disparities that violate the foundational principle of justice in medical ethics. A History of Exclusion Women’s mental health issues remain systematically excluded from and deprioritized within research and policy initiatives. Studies reveal that women are twice as likely to develop depression as men, as they face unique structural, biological, intra- and interpersonal, and cultural stressors. 1 For example, women experienced disproportionate psychological and psychiatric risk during the Covid-19 pandemic, owing to their care responsibilities, higher rates of work in the healthcare sector, and at-home duties. 2 Despite this, there remain critical gaps in the diagnosis and treatment of women’s mental health, especially during the perinatal period. 3 One such gap is the well-documented underrepresentation of women in clinical trials, even for diseases that occur predominantly in women. Despite comprising 60% of psychiatric patients, women only comprise around 40% of psychiatry clinical trial participants. 4 The problem is compounded in pregnancy and in the postpartum period, in which women remain classified as a “vulnerable population” by the FDA, despite an updated Common Rule directive to remove this designation, as well as updated 2016 recommendations by the federal Task Force on Research Specific to Pregnant Women and Lactating Women (PRGLAC). 5 Although perinatal depression is one of the most common causes of morbidity and mortality in the postpartum period, before 2019, there were no pharmacologic double blind, randomized controlled trials for perinatal depression. 6 , 7 This longstanding exclusion of pregnant and lactating individuals from research — which displaces risk from the fastidious research environment onto clinical practice and patients — violates one of medicine’s most basic principles of justice, which guides ethical allocation, access, and priority setting. 8 In this piece, we examine the case of zuranolone — from its hard-fought development to current barriers to accessibility — to highlight these pervasive and significant gaps in the research and treatment of women’s mental health conditions. Putting the Spotlight on Perinatal Mental Health Perinatal depression causes irreparable harm to mothers, children, and families. It alsocosts over 14 billion dollars to the healthcare system annually. 6 On top of the inherent sex disparity manifested by the nature of this disease, it is this country’s low-income, rural, American Indian, Black, Asian, and Hispanic populations that face the greatest symptom burden and the lowest levels of treatment initiation, participation, and benefit. 6 SSRIs and other antidepressants indicated in the treatment of major depressive disorder have historically served as the gold standard for pharmacological treatment of postpartum depression (PPD) — however, given the impact of PPD on postpartum recovery and parent-child bonding, there has been a growing call for faster-acting alternative treatment options. 9 Recent FDA approval of two reproductive neurosteroid-based medications has sparked excitement and renewed urgency for the treatment of PPD. 9 Brexanolone is a 60-hour IV infusion shown to dramatically decrease HAM-D scores in postpartum patients. Zuranolone is an oral pill taken for 14 days and shown to decrease HAM-D scores by day 3 of initiation. For many, this development represents a new era of treatment for perinatal depression and associated diseases such as premenstrual syndrome and premenstrual dysphoric disorder. Although we celebrate this advancement in basic science research, we must acknowledge the undue barriers that stood in the way of women’s mental health research and now stand in the face of our patients. A Path Full of Obstacles In 1986, allopregnanolone — the neurosteroid from which both brexanolone and zuranolone were derived — was identified as a modulator of GABA-A receptors, a class of receptors implicated in the key pathogenesis of postpartum depression. 9 Eventually, this led to the development and FDA approval of brexanolone in 2019. Factors obstructing access to brexanolone included the infusion dosage form and adherence to an FDA mandated safety protocol, which includes inpatient hospitalization for the duration of treatment. 9 Furthermore, during this time, women’s mental health continued to be severely underfunded and underresearched relative to other women’s health issues. For example, in 2018 perinatal mental health received $50 million in funding while breast cancer research received $700 million in funding, despite similar rates of perinatal mood and anxiety disorders versus breast cancer. 6 A 2021 study conducted by the U.S. National Institutes of Health determined that female-dominant diseases, including anxiety, eating disorders, and depression, were underfunded relative to male-dominant diseases. 10 Moreover, research has shown that women remain underrepresented in psychiatric clinical trials. 4 Zuranolone, approved by the FDA in August 2023, was later lauded as an effective, far more accessible alternative to brexanolone for treating PPD. However, as was the case for brexanolone, this highly desired development was hard-earned and under-supported: Dr. Jamie Maguire, whose seminal research on changes in GABAA receptor subunit expression across the perinatal period contributed directly to the eventual production of zuranolone by Sage Therapeutics, stated that her pioneering investigations received little to no federal funding. 11 Even after overcoming research funding roadblocks, zuranolone faces significant barriers to market accessibility. Since FDA approval, a fourteen-day course of zuranolone costs $15,000 and frequently lacks insurance coverage. Insurers have erected hurdles that delay or prohibit the prescription of zuranolone in contradiction with ACOG and DSM-5 guidelines. For example, Centene initially required that only psychiatrists prescribe zuranolone, effectively barring OB/GYNs from access; numerous Kaiser plans (in Colorado, Washington D.C., Maryland, and Virginia) still lack coverage policies; many state Medicaid programs (Alaska, Alabama, Mississippi, and North Carolina), as well as the Veterans Affairs national formulary, require patients to first trial alternative approved treatments for postpartum depression (e.g. SSRIs, for which a trial may take 4-6 weeks and thus dramatically delay zuranolone prescribing) or require additional comprehensive evaluations and specific diagnoses before the patient qualifies for coverage. 12 , 13 These roadblocks will serve as formidable barriers to care for all patients, from the most resource-wealthy patients to the most vulnerable, under-screened, and under-served individuals. Furthermore, these barriers exist even though zuranolone is considered a first-line treatment for postpartum depression. This represents another example of systemic barriers to life-saving medications endemic to the “kleptocapitalistic” healthcare system in the US. 14 During the third quarter of 2024, 2000 zuranolone prescriptions were delivered in the US, a 40% increase from the second quarter. 15 There remains a wide gap in treatment delivery compared to the estimated 500,000 individuals in the U.S. diagnosed with postpartum depression each year. 6 Notably, Sage Therapeutics recently announced plans to sunset brexanolone at the conclusion of 2024. 15 In other words, zuranolone will soon become the only medication for the treatment of postpartum depression — and, in fact, the only targeted medication for the treatment of any perinatal mental health disorder. Future Directions What will it take for perinatal patients to receive equitable access to treatment? Federal programs must fortify research inclusion requirements and funding for this historically neglected field. Insurance companies must publish coverage guidelines and remove unnecessary or counterproductive prerequisites. Hospital systems must establish clinical programs dedicated to the advancement of reproductive psychiatry. On the clinician scale, OB/GYN, primary care, and psychiatry clinicians all have a part to play in screening for, advocating for, and advancing treatments for perinatal depression in diverse patient populations. We encourage our colleagues across these fields to continue to strive for improved screening and treatment of this costly, harmful, undertreated, and at times deadly disease process. Conclusions The longstanding invisibility of the field of perinatal psychiatry violates the key ethical principle of justice in medicine. Against innumerable odds, perinatal depression researchers and advocates prevailed with the development of allopregnanolone-based medications brexanolone and zuranolone. However, celebration of this accomplishment must be tempered in the absence of robust women’s mental health research funding sources and insurance coverage. The systematic removal of such barriers has the potential to bolster the fight against this indisputably important and costly disease. References 1. Kuehner C: Why Is Depression More Common among Women than among Men? The Lancet Psychiatry, 2017; 4 (2): 146–58. 10.1016/S2215-0366(16)30263-2. [ DOI ] [ PubMed ] [ Google Scholar ] 2. Thibaut F and Wijngaarden-Cremers PJM: Women’s Mental Health in the Time of Covid-19 Pandemic. Frontiers in Global Women’s Health, 2020. 10.3389/fgwh.2020.588372. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Higgins A, Downes C, Monahan M, Gill A, Lamb SA, and Carroll M: Barriers to Midwives and Nurses Addressing Mental Health Issues with Women during the Perinatal Period: The Mind Mothers Study. Journal of Clinical Nursing, 2018; 27 (9–10): 1872–83. 10.1111/jocn.14252. [ DOI ] [ PubMed ] [ Google Scholar ] 4. Sosinsky AZ, Rich-Edwards JW, Wiley A, Wright K, Spagnolo PA, and Joffe H. Enrollment of Female Participants in United States Drug and Device Phase 1-3 Clinical Trials between 2016 and 2019. Contemporary Clinical Trials, 2022; 115:106718. 10.1016/j.cct.2022.106718. [ DOI ] [ PubMed ] [ Google Scholar ] 5. Hackney D, Yee LM, Hughes BL, Gyamfi-Bannerman C, Spong C: Pregnant People Can Freely Make Decisions About Participation In Clinical Research. Health Affairs Forefront, 2024. DOI: 10.1377/forefront.20241114.419371 [ DOI ] [ Google Scholar ] 6. Tobón AL, Berry OO, Gorelik S, Ryou HS, Byatt N, Cardoza K, Clare CA, Foray A, Mackie TI, Hurtado de Mendoza A, Tandon D, and Njoroge WFM: A Call To Address The Political Determinants Of Perinatal Mental Health. Health Affairs Forefront, 2024. 10.1377/forefront.20240822.518945 [ DOI ] [ Google Scholar ] 7. Dagher RK, Bruckheim HE, Colpe LJ, Edwards E, and White DB: Perinatal Depression: Challenges and Opportunities. J Womens Health (Larchmt), 2021; 30(2):154–159. doi: 10.1089/jwh.2020.8862 [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 8. Daniels N: Just Health Care. Cambridge University Press, 1985. [ Google Scholar ] 9. Patterson R, Balan I, Morrow AL, Meltzer-Brody S: Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions. Neuropsychopharmacology, 2024; 49:67–72. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Mirin AA: Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health. Journal of Women’s Health, 2021; 30 (7): 956–63. 10.1089/jwh.2020.8682. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 11. Pawluski J: Allopregnanolone to Zulresso: A Treatment for Postpartum Depression (Audio Podcast Episode 2). Mommy Brain Revisited, 2020. https://open.spotify.com/episode/4kxNd32WnTqoDtknJEVjom?si=u9QE7ct0RwqiKwliRunX_w [ Google Scholar ] 12. Burkhard J amd Murphy C: One Year Later: How Insurers Are Covering Zurzuvae, the First Postpartum Depression Pill. Policy Center for Maternal Mental Health, 2024. https://policycentermmh.org/one-year-later-how-insurers-are-covering-zurzuvae-the-first-postpartum-depression-pill/ [ Google Scholar ] 13. VA Pharmacy Benefits Management Services and National Formulary Committee: Zuranolone (ZURZUVAE) Criteria for Use. VA Pharmacy Benefits Management Services, 2024. https://www.va.gov/formularyadvisor/drugs/4042825-ZURANOLONE-CAP-ORAL [ Google Scholar ] 14. Berwick DM: Salve Lucrum: The Existential Threat of Greed in US Health Care. JAMA, 2023; 329(8):629–630. 10.1001/jama.2023.0846 [ DOI ] [ PubMed ] [ Google Scholar ] 15. Sage Therapeutics, Inc.: Sage Therapeutics Announces Third Quarter 2024 Financial Results and Highlights Pipeline and Business Updates. 2024. https://investor.sagerx.com/news-releases/news-release-details/sage-therapeutics-announces-third-quarter-2024-financial-results#:~:text=Sage%20plans%20to%20sunset%20ZULRESSO,available%20until%20December%2031%2C%202024%20 ACTIONS View on publisher site PDF (45.5 KB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

Related documents

• Reproductive health - a blind spot in psychotherapeutic treatment? Evidence of insufficient consideration of reproductive factors in routine care.#120209
• Reproductive health – a blind spot in psychotherapeutic treatment? Evidence of insufficient consideration of reproductive factors in routine care#130479
• Psychiatric History and Postpartum Depression: The Mediating Role of Obstetric Complications.#425144
• Postpartum Depression and Cesarean Section#857020
• Measuring moral distress in Swedish maternal and neonatal healthcare: validation of an adapted MDS‑R and development of a criterion‑based index.#182295