{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:24:16Z","timestamp":1787408656048,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Given the increasing prevalence of postpartum depression (PPD) and the stigma associated with this condition, it is essential to address this significant health concern. Brexanolone is an FDA\u2010approved treatment for PPD that works by positive\u2010allosteric modulation of type A \u03b3\u2010aminobutyric acid (GABA\n                    <jats:sub>A<\/jats:sub>\n                    ) receptors. As an intravenous version of allopregnanolone, brexanolone is known for its rapid onset of action and lasting impact on depressive symptoms in patients with PPD, with significant reductions in depressive symptoms observed by the end of the 60\u2010h infusion and improvements maintained through Day 30 of follow\u2010up. The quick onset is particularly important as traditional first\u2010line treatment for PPD can take up to several weeks to produce observable improvements. Despite its efficacy, the clinical use of brexanolone is limited by the need for a continuous 60\u2010h intravenous infusion and mandatory enrollment in Risk Evaluation and Mitigation Strategy (REMS) program due to risks of excessive sedation and sudden loss of consciousness. Brexanolone is metabolized through non\u2010CYP\u2010mediated pathways, including keto\u2010reduction, glucuronidation, and sulfation; therefore, no dose adjustments are required in patients with mild to severe renal impairment (eGFR 15\u201389\u2009mL\/min\/1.73\u2009m\n                    <jats:sup>2<\/jats:sup>\n                    ). However, its use should be avoided in end\u2010stage renal disease (eGFR &lt;\u200915\u2009mL\/min\/1.73\u2009m\n                    <jats:sup>2<\/jats:sup>\n                    ) due to potential accumulation of its solubilizing vehicle, betadex sulfobutyl ether sodium. While primarily indicated for PPD, brexanolone is under investigation for post\u2010traumatic stress disorder, alcohol use disorder, postpartum psychosis, and tinnitus. Future research focusing on alternative delivery methods and expanded therapeutic indications could make brexanolone more accessible and broaden its clinical utility.\n                  <\/jats:p>","DOI":"10.1111\/cts.70671","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T03:38:28Z","timestamp":1786073908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brexanolone, a First\u2010In\u2010Class Neurosteroid Medication: Mechanism of Action, Clinical, and Translational Science"],"prefix":"10.1111","volume":"19","author":[{"given":"Laura","family":"Gayanova","sequence":"first","affiliation":[{"name":"Duquesne University Nasuti College of Osteopathic Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Sian","sequence":"additional","affiliation":[{"name":"Duquesne University Nasuti College of Osteopathic Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Wells","sequence":"additional","affiliation":[{"name":"Duquesne University Nasuti College of Osteopathic Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7743-9453","authenticated-orcid":false,"given":"Amber","family":"Fedin","sequence":"additional","affiliation":[{"name":"Duquesne University Nasuti College of Osteopathic Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7535-3340","authenticated-orcid":false,"given":"YanFei","family":"Qi","sequence":"additional","affiliation":[{"name":"Duquesne University Nasuti College of Osteopathic Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190020979627"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01663-6"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.46486"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6919a2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-019-01121-0"},{"key":"e_1_2_12_7_1","unstructured":"National Center for Biotechnology Information \u201cPubChem Compound Summary for CID 92786 Allopregnanolone\u201d."},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31264-3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31551-4"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-023-06427-2"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01155-w"},{"key":"e_1_2_12_12_1","unstructured":"U.S. Food and Drug Administration \u201cMulti\u2010Disciplinary Review and Evaluation: NDA 211371 (Zulresso [Brexanolone] Injection) \u201davailable at FDA Multi\u2010Disciplinary Review and Evaluation: NDA 211371 (Zulresso [Brexanolone] Injection)."},{"key":"e_1_2_12_13_1","unstructured":"Center for Drug Evaluation and Research \u201cMulti\u2010Disciplinary Review and Evaluation: ZULRESSO (Brexanolone) Injection (sNDA 211371 S\u2010007) \u201davailable at FDA ZULRESSO (Brexanolone) sNDA 211371 S\u2010007 Review."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.11.149"},{"issue":"2","key":"e_1_2_12_15_1","article-title":"Temporal Dynamics of Antidepressant Response Following Brexanolone Treatment in Postpartum Depression","volume":"87","author":"Kozik R.","year":"2026","journal-title":"Journal of Clinical Psychiatry"},{"key":"e_1_2_12_16_1","unstructured":"\u201cAssessment of Safe\u2010Use Conditions for Administration of ZULRESSO in a Home Setting\u201d available at https:\/\/clinicaltrials.gov\/study\/NCT0509600."},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25008"},{"key":"e_1_2_12_18_1","unstructured":"\u201cA Randomized Double\u2010Blind Placebo\u2010Controlled Study to Evaluate the Efficacy and Safety of SAGE\u2010547 Injection in the Treatment of Subjects With Super\u2010Refractory Status Epilepticus \u201dAvailable at https:\/\/clinicaltrials.gov\/study\/NCT02477618."},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2025.10.017"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1662226"},{"key":"e_1_2_12_21_1","unstructured":"\u201cA Study of Brexanolone for Acute Respiratory Distress Syndrome due to COVID\u201019 \u201dAvailable at https:\/\/clinicaltrials.gov\/study\/NCT04537806."},{"key":"e_1_2_12_22_1","unstructured":"\u201cUtility of Brexanolone to Target Stress\u2010Induced Alcohol Use Among Men and Women With Posttraumatic Stress Disorder \u201dAvailable at https:\/\/clinicaltrials.gov\/study\/NCT05223829."},{"key":"e_1_2_12_23_1","unstructured":"\u201cBrexanolone to Target Concurrent Posttraumatic Stress Disorder (PTSD) and Stress Induced Alcohol Use in Veterans: A Dose Finding Study \u201dAvailable at https:\/\/clinicaltrials.gov\/study\/NCT06580444."},{"key":"e_1_2_12_24_1","unstructured":"\u201cExpanded Access Protocol of ZULRESSO\u2122 (Brexanolone) Injection for Adult Patients With Postpartum Depression \u201dAvailable at https:\/\/clinicaltrials.gov\/study\/NCT03924492."}],"container-title":["Clinical and Translational 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