Zulresso (brexanolone) / Ligand, Supernus Pharma - LARVOL DELTA

Pregnenolone to Target Concurrent PTSD and Stress Induced Alcohol Use in Veterans: A Dose Finding Study (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Trial completion date: Mar 2027 ➔ Dec 2027 | Trial primary completion date: Feb 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol) • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms. (PubMed, CNS Drugs) - "Following the US Food and Drug Administration (FDA) approval of esketamine and brexanolone in 2019, industry investment in therapeutics with novel mechanisms for mood and anxiety disorders has expanded, catalyzing a new wave of innovative interventions...The drug names discussed are ALTO-100, ALTO-203, ALTO-207, ALTO-300, BHV-7000, BI-1569912, BPL-003, COMP360, DT120, ELE-101, GATE-251, GH001, GM-1020, GM-2505, HLP003, MK-1942, NBI-1065845, NBI-1070770, NV-5138, PIPE-307, SEP-363856, SPT-300, VLS-01, and XEN1101. The US Clinical Trials registry (clinicaltrials.gov), MEDLINE, conference proceedings, and company communications such as press releases were consulted to obtain up-to-date trial information and reported outcomes. Overall, the therapeutic landscape shows an expanding range of clinical compounds under active development; nonetheless, persistent challenges remain, including approaches to therapeutics where functional unblinding may occur, the ways in which to..."

Journal • P2/3 data • Review • CNS Disorders • Mood Disorders • Psychiatry

BLOOM: Brexanolone Lifting Outcomes Of Moms (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Lipocine Inc.

New P3 trial • 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

Brexanolone, a First-In-Class Neurosteroid Medication: Mechanism of Action, Clinical, and Translational Science. (PubMed, Clin Transl Sci) - "While primarily indicated for PPD, brexanolone is under investigation for post-traumatic 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."

Journal • Review • Addiction (Opioid and Alcohol) • Anesthesia • Chronic Kidney Disease • CNS Disorders • Depression • Mood Disorders • Nephrology • Otorhinolaryngology • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry • Renal Disease

Pediatric Extrapolation in Neuropsychiatric Drug Development: Leveraging Pharmacokinetic and Pharmacodynamic Strategies to Facilitate FDA Approvals. (PubMed, Clin Pharmacol Ther) - "Case examples spanned broad age ranges, from mechanistically informed neonatal applications utilizing enzyme maturation modeling (risdiplam) to adolescent populations where adult dosing regimens proved adequate (brexanolone, nipocalimab). Additionally, pharmacodynamic biomarkers were pivotal in pediatric extrapolation of eculizumab and nipocalimab efficacy for the treatment of generalized myasthenia gravis, highlighting promising future directions for the field. These cases demonstrate how achieving comparable pharmacokinetics and, when necessary, pharmacodynamics profiles between adult and pediatric populations can support efficient regulatory approval without dedicated pediatric efficacy studies. The regulatory pathways established for select neuropsychiatric indications provide a compelling framework for expanding extrapolation approaches to other therapeutic areas."

FDA event • Journal • PK/PD data • Review • CNS Disorders • Myasthenia Gravis • Pediatrics • 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

Pharmacokinetic Study for IV Allopregnanolone (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: Boston University | N=256 ➔ 11 | Recruiting ➔ Terminated; The investigator moved to another institution; only preliminary data from pharmacokinetic studies were collected at Boston University School of Medicine/Boston Medical Center.

Enrollment change • Trial termination • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Innovations in Depression Diagnosis and Treatment: A Review of Biological, Cognitive, and Psychosocial Advances. (PubMed, Curr Top Med Chem) - "Advances in treatment span from FDA-approved neurosteroid therapies for postpartum depression (e.g., brexanolone) to breakthrough psychedelic-assisted psychotherapy for treatment-resistant cases...Finally, we address the heightened vulnerability of special populations-adolescents, older adults with comorbid dementia, and women in the peripartum period, and propose interdisciplinary models to close critical gaps in global mental health. This review highlights the need for a holistic and personalized approach to depression care, aiming to reduce healthcare disparities and improve long-term outcomes."

Journal • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Dementia • Depression • Inflammation • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

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

An Open Label Pilot Study of IV Brexanolone for the Treatment of Post-Traumatic Stress Disorder (clinicaltrials.gov) - P4 | N=10 | Terminated | Sponsor: Donald Jeffrey Newport | N=20 ➔ 10 | Recruiting ➔ Terminated; Loss of funding.

Enrollment change • Trial termination • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

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

The PNEI Nexus: Multidirectional Interactions Between Alimentary Humoral Immunological Dermatological and Psychiatric Systems. (APA 2026) - "Neurosteroids & Hormonal Modulation: Brexanolone, a neurosteroid approved for postpartum depression, regulates GABAergic signaling and neuroimmune interactions. ?...NMDA Modulation: Ketamine and esketamine rapidly alleviate depression by modulating glutamatergic and inflammatory pathways. ?...Objective Four: Apply integrative strategies in clinical practice that leverage PNEI insights to enhance mental health outcomes. Objective Five: Evaluate the implications of PNEI-informed models for interdisciplinary collaboration and workforce development in psychiatry.; Objective One: Describe the core components of the psychoneuroendocrinoimmunology (PNEI) model and its relevance to psychiatric disorders..; Objective Two: Identify key pathways linking the gut microbiota, endocrine system, immune responses, and skin to brain function and behavior.; Objective Three: Examine emerging psychiatric treatments targeting PNEI pathways, including neurosteroids, immune modulators, and..."

Atopic Dermatitis • CNS Disorders • Cognitive Disorders • Depression • Developmental Disorders • Endocrine Disorders • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammation • Mental Retardation • Mood Disorders • Postpartum Depression • Psoriasis • Psychiatry • Schizophrenia

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

Should Brexanolone, a neurosteroid antidepressant, be recommended for the management of postpartum depression? (ACOG 2026) - "Abstract is embargoed at this time."

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

Perinatal Depression: Current Knowledge. (PubMed, Adv Exp Med Biol) - "Other than brexanolone, no medications are FDA-approved for the treatment of PND at present and, apart from pharmacotherapy, patient and family education are crucial for optimal outcomes, emphasizing the importance of a multidisciplinary approach for the management of PND. Other aspects of that disorder, such as transcultural factors, stigma, and the importance of timely screening are also discussed."

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

Temporal Dynamics of Antidepressant Response Following Brexanolone Treatment in Postpartum Depression. (PubMed, J Clin Psychiatry) - P | "These findings could have broader implications for understanding the pathophysiology of mood disorders and for developing targeted interventions that modulate brain dynamics to promote recovery from pathological affective states. Trial Registration: ClinicalTrials.gov identifier: NCT05543746."

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

Neuroactive Steroid Regulation in Premenstrual Dysphoric Disorder: Cross-Integration of Metabolism, Dysfunction, Neurobiology, and Precision Medicine. (PubMed, Curr Neuropharmacol) - "NAS-targeted therapies, such as Brexanolone and Sepranolone, along with oral contraceptives, also demonstrate therapeutic efficacy. Targeting NAS-related pathways offers promising therapeutic strategies, as exemplified by recent advances in targeted drug development and individualized medicine. This review provides a foundation for precision medicine in PMDD and related psycho-neuroendocrine disorders, promoting future research into mechanism-based diagnostics and treatments."

Journal • CNS Disorders • Depression • Metabolic Disorders • Mood Disorders • Psychiatry • PGR

Shared neuroendocrine mechanisms in Premenstrual Dysphoric Disorder (PMDD), Postpartum Depression (PPD), and Perimenopausal Affective Disorders: the role of progesterone, allopregnanolone, and cortisol (ISGE 2026) - "Interventions: Pharmacologic modulation of GABAergic tone through neurosteroids (brexanolone, zuranolone) or neurosteroid antagonists (sepranolone). PMDD, PPD, and perimenopausal depression share a unified neuroendocrine mechanism involving ALLO–GABAA receptor dynamics, HPA imbalance, and neuroinflammation. These disorders reflect a continuum of hormonal sensitivity, and neurosteroid-based GABAergic modulation provides a path to emotional stabilization."

CNS Disorders • Depression • Inflammation • Mood Disorders • Postpartum Depression • Psychiatry • BDNF • IL6