Zurzuvae (zuranolone) / Shionogi, Biogen, Supernus Pharma - LARVOL DELTA

Influence of the Neuroactive Steroids Allopregnanolone and Zuranolone on Inhibitory Neurotransmission and Synaptic Organization in the context of GlyR autoantibodies (Neuroscience 2026) - "GlyR autoantibodies are known to reduce glycinergic inhibition, specifically glycine potency. Our data thus far indicate that patient-derived autoantibodies induce an increase in excitation that can be partially counteracted by the application of NAS, highlighting their potential as pharmacological agents against neurological diseases affecting the inhibition-excitation balance."

CNS Disorders • Depression

ZURZUVAE Capsules 30mg Drug Use-results Survey (clinicaltrials.gov) - P=N/A | N=1500 | Enrolling by invitation | Sponsor: Shionogi & Co., Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • CNS Disorders • Depression • Mood Disorders • Psychiatry

Zuranolone in Postpartum Depression: Mechanistic Innovation, Clinical Evidence, and Translational Uncertainty. (PubMed, Cureus) - "In addition, zuranolone was not approved as a broad treatment for major depressive disorder, underscoring the need to avoid extrapolating postpartum depression findings to all depressive populations. Overall, zuranolone should be understood as a meaningful but evidence-bounded innovation in perinatal psychopharmacology, whose clinical value will depend on careful patient selection, safety counseling, follow-up, equitable access, and continued evidence generation."

Journal • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Profiling zuranolone as a treatment option for postpartum depression. (PubMed, Expert Rev Neurother) - "However, evidence for long-term outcomes is limited due to the lack of comparative trials with other active treatments for postpartum depression and the exclusion of lactating populations or those with psychiatric comorbidities. More studies are needed to define the full scope of its clinical applicability."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Safety evaluation of zuranolone in the management of postpartum depression: A real-world pharmacovigilance study using the FDA adverse event reporting system (FAERS). (PubMed, Australas Psychiatry) - "Prospective clinical studies are warranted for continued monitoring of rare or long-term AEs. Further safety evaluations and clinical management strategies are essential."

Adverse events • Journal • Real-world evidence • Anesthesia • Bipolar Disorder • CNS Disorders • Depression • Insomnia • Mental Retardation • Mood Disorders • Movement Disorders • Postpartum Depression • Psychiatry • Sleep Disorder • Suicidal Ideation

A Study to Learn More About How Zuranolone Affects Postpartum Depression Symptoms in Participants Who Took it Within 1 Year After The End of Their Pregnancy (clinicaltrials.gov) - P=N/A | N=305 | Completed | Sponsor: Biogen | Recruiting ➔ Completed | N=200 ➔ 305

Enrollment change • Real-world evidence • Trial completion • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

A Long-Term Study of Patient-Reported Changes in Postpartum Depression Symptoms in People Starting Zuranolone (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Biogen | N=200 ➔ 300

Enrollment change • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

The neurosteroid paradigm in perinatal depression: From pathophysiology to precision therapeutics. (PubMed, J Neuroendocrinol) - "We synthesize current clinical experience with brexanolone and zuranolone in the treatment of PPD, highlighting efficacy and practical considerations. Finally, we explore emerging precision medicine approaches that leverage the heterogeneity of clinical presentations and treatment responses in PPD to guide the development of targeted therapeutic strategies for this widely prevalent and debilitating condition."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Allopregnanolone (Zuranolone) in Post-stroke Depression (clinicaltrials.gov) - P2 | N=6 | Recruiting | Sponsor: Duke University | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Cardiovascular • CNS Disorders • Depression • Mood Disorders • Psychiatry

Potential of Neurosteroids for Precision Medicine in Psychiatry. (PubMed, Biol Psychiatry) - "Exciting emerging studies suggest that a biomarker indicating altered or a reduced capacity for endogenous neurosteroidogenesis would be beneficial for identifying individuals at risk for postpartum depression and could potentially predict treatment response to neurosteroid-based treatments. This review aims to provide a comprehensive report on the production of endogenous neurosteroids in the brain, the current clinical landscape for the use of neurosteroid-based therapies in psychiatry, and the potential utility of measuring neurosteroidogenesis capacity as a biomarker for the diagnosis and treatment of psychiatric illnesses."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

Real-world adverse event profiles of Zuranolone and Brexanolone based on FAERS and VigiAccess databases: An observational study. (PubMed, Medicine (Baltimore)) - "Zuranolone's AEs mainly involved nervous system disorders and Psychiatric disorders, while Brexanolone's primarily included Injury, poisoning and procedural complications, and Psychiatric disorders. This study would provide more safety reference data for the clinical use of two drugs."

Adverse events • Journal • Observational data • Real-world evidence • CNS Disorders • Depression • Fatigue • Mental Retardation • Otorhinolaryngology • Postpartum Depression • Psychiatry • Vertigo

Comparative efficacy and acceptability of pharmacological interventions for postpartum depression: a systematic review and network meta-analysis. (PubMed, Psychiatry Res) - "Current RCT evidence suggests that saffron, fluoxetine, esketamine, brexanolone, and zuranolone may improve symptoms of PPD. Brexanolone may have a potentially unfavourable acceptability signal, while zuranolone was associated with increased adverse event incidence. However, the evidence is limited by sparse networks, limited active-comparator evidence, imprecision in some estimates, and clinical heterogeneity, and should therefore be interpreted with caution."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

First Reported Case of Dissociative Symptoms Associated With Zuranolone Use in Peripartum Depression. (PubMed, Cureus) - "While selective serotonin reuptake inhibitors remain a mainstay of treatment, novel neurosteroid-based therapies such as brexanolone and zuranolone offer promising, rapid-acting alternatives.  We have reported the first known case of dissociative symptoms temporally associated with zuranolone use. Given the growing use of zuranolone in primary care and obstetrical and gynecological settings where psychiatric consultation may be limited or absent, clinicians should be vigilant for dissociative symptoms, especially in trauma-exposed populations. This report underscores the need for thorough psychiatric evaluation before initiating neurosteroid treatment and highlights gaps in access to psychiatric care that may hinder optimal management of complex peripartum presentations."

Journal • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Obstetrics • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry

Targeting Neuroendocrine Pathways in Major Depression: A Pharmacological Review (CINP 2026) - "Mifepristone, a glucocorticoid receptor antagonist, has demonstrated significant symptom reduction in patients with psychotic depression, whereas other agents acting on this axis have not consistently produced favorable results.Regarding the thyroid axis, adjunctive treatment with triiodothyronine (T3) has demonstrated antidepressant-enhancing effects.Hormonal replacement therapy has also been shown to ameliorate depressive symptoms in postmenopausal women, particularly those experiencing vasomotor symptoms.Allopregnanolone derivatives like brexanolone and zuranolone can rapidly alleviate postpartum depressive symptoms. Neuroendocrine dysregulation contributes to the pathogenesis of MDD. Given that approximately 15-30% of patients fail to respond to at least two adequate trials of conventional antidepressants, exploring alternative pharmacological strategies is clinically relevant. Modulating neuroendocrine pathways may represent a promising approach to improving..."

Late-breaking abstract • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Zuranolone mitigates delirium-like bispectral EEG changes, behavioral deficits, and neuroinflammation across surgical and inflammatory mouse models and age groups. (PubMed, bioRxiv) - "Finally, in young mice, zuranolone improved a composite behavioral severity score in the LPS model, whereas behavioral effects in the POD model were modest and domain-specific. Together, these findings support zuranolone as a candidate strategy to reduce delirium-like electrophysiological and neuroimmune abnormalities, with the strongest effects in inflammation-driven and age-vulnerable contexts."

Journal • Preclinical • CNS Disorders • Inflammation • CD68

Next-Generation Pharmacotherapy for Depressive Disorders: From Novel Compounds to Optimized Use of Available Drugs. (PubMed, Drug Des Devel Ther) - "Representative next-generation approaches include N-methyl-D-aspartate (NMDA) receptor modulators and other rapid-acting agents, dextromethorphan-bupropion, multimodal antidepressants, neuroactive steroid-related therapies such as brexanolone and zuranolone, psychedelic-assisted pharmacotherapy, kappa-opioid receptor antagonists, and bipolar-relevant mood-stabilizing pharmacotherapies. Current evidence suggests that progress in depression pharmacotherapy depends not only on developing new compounds, but also on improving treatment selection, sequencing, monitoring, tolerability management, and sustained use in heterogeneous clinical populations. A next-generation framework should therefore integrate novel drug classes with improved use of established agents, while remaining sensitive to differences among unipolar depression, bipolar depression, and TRD."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Response to Durability of zuranolone in postpartum depression versus major depressive disorder. (PubMed, Psychiatry Clin Neurosci) - "This article relates to Response to Durability of zuranolone in postpartum depression versus major depressive disorder."

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Pharmacotherapeutic approaches to treating postpartum depression: a focus on GABAA receptor positive allosteric modulators. (PubMed, Expert Opin Pharmacother) - "We review clinical trial data supporting the efficacy, safety, and rapid onset of brexanolone and zuranolone, as well as their sustained antidepressant effects. Positive allosteric modulators of GABAAR represent a novel and promising approach to the treatment of PPD, with rapid and sustained antidepressant effects. These agents may ultimately have broader applications across psychiatric disorders characterized by GABAergic dysfunction, although further research is needed to clarify their role and optimize their use."

Journal • Review • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Postpartum Depression • Psychiatry

Neuroendocrine and neuroinflammatory mechanisms in postpartum depression: From hormonal withdrawal to central immune dysregulation and emerging therapeutic targets. (PubMed, J Psychiatr Res) - "We evaluate established and emerging therapeutic strategies, including conventional antidepressants, FDA-approved neuroactive steroids (brexanolone, zuranolone), and novel immune-targeted interventions (NLRP3 inhibitors, cytokine antagonists). By integrating biological, genetic, and psychosocial risk factors, this review provides a precision-medicine framework for targeting neuroinflammatory pathways, particularly TLR-mediated immune activation, alongside conventional treatments, while identifying NLRP3 inflammasome signaling as a promising but clinically unvalidated therapeutic target warranting direct investigation in postpartum populations."

Journal • Review • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Postpartum Depression • Psychiatry • IL1B • IL6 • NLRP3 • TNFA

Assessment of Brexanolone's and Zuranolone's Efficacy in Management of Postpartum Depression (APA 2026) - "Description Abstract Background Postpartum depression has been linked to changes in levels of allopregnanolone, a neurosteroid metabolite of progesterone that modulates GABA type A receptors allosterically. While associated with adverse effects, this medication should be compared to current standard therapies to evaluate its potential in treating PPD. These studies emphasize the need to investigate rapid, sustainable and effective treatments for this population and explore the use of neurosteroid GABA receptor- positive allosteric modulators in this context group."

Clinical • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Global Perspectives on CNS Drug Innovation: Achievements, Barriers, and Priorities for the Next Decade. (PubMed, Int J Neuropsychopharmacol) - "To convert momentum into durable progress, we recommend: (i) deeper academia-industry/stakeholder collaboration and sustained funding for high-risk/high-reward science from industry, governments and non-for profit foundations; (ii) modernized regulation (flexible evidentiary paths, novel endpoints, and clear guidance on adaptive/platform trials); (iii) data-driven development integrating RWE, AI/ML, and precision medicine; (iv) the adoption of Neuroscience-based Nomenclature (NbN); and (v) a global-access mandate with essential-medicine inclusion, equitable pricing/licensing, capacity building, tele-enabled mental health, and geographically diverse research. Aligning scientific innovation with implementation and equity can accelerate translation and ensure new treatments benefit patients worldwide."

Journal • Alzheimer's Disease • CNS Disorders • Depression • Insomnia • Mood Disorders • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Sleep Disorder • NBN

Analysis of depressive symptom trajectory patterns with zuranolone: Time-series clustering of Japanese Phase 2 and Phase 3 trial data. (PubMed, PCN Rep) - "No notable differences were observed among clusters in baseline demographics, episode duration, or initial severity. This study reveals diverse symptom trajectories in zuranolone-treated patients and provides clinically relevant insights, highlighting the importance of early post-dosing monitoring-particularly of sleep symptoms-to inform clinical management and future research."

Clinical • Journal • P2 data • P3 data • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sleep Disorder

Updated guidelines for pharmacologic treatment of perinatal depression: Understanding medication options. (PubMed, Cleve Clin J Med) - "The 2023 American College of Obstetricians and Gynecologists (ACOG) guideline on perinatal mental health conditions recommends prescribing and titrating pharmacotherapy for perinatal depression, with the selective serotonin reuptake inhibitors sertraline and escitalopram as first-line medications for patients who have not previously taken any medications for mood disorders. A subsequent ACOG Clinical Practice Update addresses zuranolone for postpartum depression. The authors present an overview of the guideline's recommendations on pharmacotherapy for treating perinatal depression and summarize actionable recommendations for nonpsychiatric clinicians."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Obstetrics • Postpartum Depression • Psychiatry

Pregnanolone-Based Prodrugs as a Strategy for Neuroprotective Drug-Like Compounds: Pregnanolone Pyroglutamate and Its Age‑dependent Anticonvulsant Effects in the 6-hz Seizure Model in Immature Rats. (PubMed, Drug Des Devel Ther) - "Their in vivo activity was evaluated in the 6-Hz transcorneal stimulation model in 15‑ and 25‑day‑old Wistar rats, with detailed quantification of seizure duration and severity, and direct comparison to the endogenous neurosteroid allopregnanolone and the approved neuroactive steroid zuranolone...These findings validate a pregnanolone‑prodrug approach in which C‑3 masking groups are used primarily to deliver and release endogenous pregnanolone in vivo, and they identify compound 1 as a lead candidate for further optimization as an anticonvulsant for pediatric epilepsy. The work provides a translationally relevant framework for developing neurosteroid‑based prodrugs with improved drug‑like properties for pharmacoresistant seizures in the developing brain."

Journal • Preclinical • CNS Disorders • Epilepsy • Pediatrics

Examining New Mothers' Access to Zuranolone. (PubMed, Ochsner J) - No abstract available

Journal