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

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

▼Zuranolone for the treatment of moderate or severe postnatal depression. (PubMed, Drug Ther Bull) - No abstract available

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

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

Antiseizure Medications that Did Not Reach the Epilepsy Market: An Assessment of Factors Contributing to Their Failed Clinical Development Over the Last Three Decades. (PubMed, Drugs) - "Compounds whose development was terminated include atimepazole, beprodone, cannabidivarin, carabersat, conantokin-G, dezinamide, elpetrigine, flunarizine, fluorofelbamate, ICA-105665, isovaleramide, JNJ-40411813, losigamone, naluzotan, padsevonil, pitolisant, ralitoline, remacemide, safinamide, soretolide, talampanel, tonabersat, T2000, T2007, valnoctamide, valrocemide, VX-765, zandatrigine, zuranolone, and 534U87. In some instances, failure to pursue an epilepsy indication could be explained by prioritization of development for other neurological or psychiatric conditions. This may reflect the perception of the drug market for common epilepsies being relatively crowded, and only attractive for compounds with outstanding safety or efficacy advantages over existing medications."

Journal • Review • CNS Disorders • Epilepsy • Psychiatry

The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives. (PubMed, Neurosci Biobehav Rev) - "This review synthesizes current evidence on how neurosteroids (and, more broadly, neuroactive steroids) contribute to the endogenous regulation of neural excitability, affective reactivity, and immune signaling, and explores how their dysregulation may represent a shared mechanism of vulnerability across diverse brain disorders. Finally, we highlight emerging therapeutic opportunities, underscored by recent advances such as zuranolone and ganaxolone, and discuss future challenges in optimizing delivery, enhancing receptor specificity, and refining clinical trial design to establish neurosteroid-based interventions as a versatile platform for treating and preventing complex neuropsychiatric disease."

Journal • Review • Autism Spectrum Disorder • Bipolar Disorder • CNS Disorders • Depression • Epilepsy • Genetic Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Multiple Sclerosis • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Tic Disorders • Tourette Syndrome

Safety and efficacy of zuranolone in Japanese adults with major depressive disorder: An open-label, repeated-treatment part of a Phase 3 clinical trial. (PubMed, PCN Rep) - "The HAMD-17 total score decreased by 8 and 15 days after the initiation of zuranolone in all six cycles, and there were no meaningful differences in the HAMD-17 total score reduction across treatment cycles. In this open-label part of the Phase 3 study in Japan, zuranolone decreased the HAMD-17 total scores from baseline over 15 days during repeated treatment cycles in patients with major depressive disorder, without any new safety signals."

Journal • P3 data • CNS Disorders • Depression • Infectious Disease • Major Depressive Disorder • Mood Disorders • Psychiatry

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

New trial • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Zuranolone as a Novel Therapy for Postpartum Depression: A Narrative Review of Current Evidence and Future Directions. (PubMed, Cureus) - "This narrative review outlines the evolving evidence base for zuranolone, including current understanding of its efficacy and tolerability, and explores practical considerations for its use. The potential role of zuranolone within the broader treatment landscape is discussed, alongside key uncertainties regarding duration of effect, longer-term outcomes and accessibility. By synthesising available literature and identifying key knowledge gaps, this review aims to clarify the evolving role of zuranolone in the treatment of PPD, while highlighting priorities for future research and clinical practice."

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

Biogen reports strong fourth quarter and full year 2025 results and provides full year 2026 financial guidance (Biogen Press Release) - "LEQEMBI fourth quarter global in-market sales of approximately $134 million, up 54% year-over-year, with U.S. in-market sales of approximately $78 million, representing continued growth; SKYCLARYS grew global patients on therapy by approximately 30% in 2025; fourth quarter U.S. revenue of approximately $89 million driven by demand growth, with ex-U.S. revenue of approximately $44 million reflecting continued demand growth, also impacted by a one-time reimbursement true-up; ZURZUVAE fourth quarter revenue of approximately $66 million showed strong continued demand growth; VUMERITY grew 3% year-over-year in the fourth quarter; SPINRAZA fourth quarter revenue declined 15% year-over-year, impacted by timing of shipments outside the U.S., with full year revenue down 2% year-over-year."

Commercial • Alzheimer's Disease • Depression • Friedreich ataxia • Multiple Sclerosis • Muscular Atrophy • Ocular Inflammation • Pain • Parkinson's Disease

Zuranolone: A case study in (regulatory) rush to judgement? (PubMed, Br J Clin Pharmacol) - "We examine the clinical trial data submitted by the manufacturer for zuranolone and discuss how regulatory bodies may be failing in their role as gatekeepers. The approval of zuranolone for PPD can thus be seen as a case study for recent developments in drug regulatory sciences."

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

A systematic safety assessment of zuranolone: real-world adverse event analysis from the FAERS database. (PubMed, Arch Womens Ment Health) - "Enhanced monitoring for AEs related to nervous system disorders and psychiatric disorders is required during the clinical use of Zuranolone."

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

Addressing the Global Mental Health Crisis: How a Human Rights Approach Can Help End the Search for Pharmaceutical Magic Bullets. (PubMed, Health Hum Rights) - "I discuss the marketing of postpartum distress (PPD) as a disorder of the hypothalamic-pituitary-adrenal axis and the "first ever" pill to treat PPD, zuranolone, as a case illustration of medicalization. I conclude by offering solutions for reform that are embedded in a human rights framework."

Journal • Psychiatry

Current treatment options for perinatal depression. (PubMed, Curr Opin Obstet Gynecol) - "Timely diagnosis and individualized treatment of PND are essential for optimizing maternal and neonatal outcomes. Individualized, evidence-based treatment, including pharmacologic and nonpharmacologic options, can improve outcomes for both the parent and fetus or infant. New therapies and digital innovations hold promise but require careful integration into practice."

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

Assessing the utility of the neurosteroid zuranolone to modify alcohol-related behaviours. (PubMed, Neuropharmacology) - "Overall, our data do not show robust reductions in alcohol intake following zuranolone administration across dosing schedules in either sex in preclinical models of binge drinking. Future studies are required to explore its potential relevance in comorbid AUD and affective disorders."

Journal • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Depression • Postpartum Depression • Psychiatry

Molecular Mechanisms of Emerging Antidepressant Strategies: From Ketamine to Neuromodulation. (PubMed, Int J Mol Sci) - "We then focus on emerging therapies targeting the glutamatergic, GABAergic, and dopaminergic systems, including ketamine, esketamine, (R)-ketamine, the dextromethorphan-bupropion combination (DMX-BUP), neurosteroids (zuranolone, brexanolone), as well as selective serotonin receptor modulators (gepirone ER) and dopaminergic modulators (cariprazine). The review is complemented by a discussion of non-pharmacological neuromodulatory approaches, such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and photobiomodulation. Rather than providing another summary of clinical response indicators, this article integrates the molecular underpinnings of novel antidepressant agents and neuromodulation techniques with current concepts of depression pathophysiology, highlighting their relevance for the development of precise, mechanistically targeted, and multimodal treatment strategies."

Journal • Review • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Psychiatry

Health Canada approves first drug specifically made to treat moderate to severe postpartum depression (MSN News) - "Patients with ZURZUVAE showed an average reduction of 17.8 points while those with a placebo showed an average reduction of 13.2 points in the 17-item Hamilton Rating Scale, both in day 15 of treatment."

Canada approval • Postpartum Depression

Durability of zuranolone in postpartum depression versus major depressive disorder. (PubMed, Psychiatry Clin Neurosci) - "The antidepressant effect of zuranolone appears to be sustained beyond the treatment period in postpartum depression, whereas in major depressive disorder it may not persist after treatment discontinuation."

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

Shionogi has received Japanese regulatory approval to manufacture and market ZURZUVAE Capsules 30 mg (zuranolone) for the treatment of depression and depressive states, following positive Phase 3 trial results in adults with major depressive disorder. (TipRanks)

Japan approval • Major Depressive Disorder

Comparison of Zuranolone, Brexanolone, and Sertraline in the Treatment of Postpartum Depression (ASHP 2025) - No abstract available

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

Sustainable Spectrofluorometric Method for the Determination of Zuranolone in Pharmaceutical Formulations Using Propidium Iodide Ion-Pair Complex. (PubMed, Luminescence) - "Application to Zurzuvae capsules demonstrated excellent accuracy and reliable analytical performance. Furthermore, high Analytical GREEnness and favorable Green Analytical Procedure Index scores highlighted the method's environmental sustainability, positioning it as a robust, eco-friendly tool for routine analysis."

Journal

Health Canada has granted a Notice of Compliance (NOC) to Biogen for its drug Zurzuvae, which is classified as a New Active Substance (NAS). (GeneOnline) - "The approval designates Zurzuvae as a treatment option for women experiencing moderate or severe postpartum depression (PPD)."

Canada approval • Postpartum Depression

Postpartum depression pill gets approval in a 1st for Canada (Global News) - "Zuranolone, sold under the brand name Zurzuvae, is a pill taken once a day for 14 days and can start relieving depressive symptoms in as few as three days."

Canada approval • Postpartum Depression

Editorial: Enhancing therapeutic strategies: a focus on pharmacovigilance in new wave antidepressants and antipsychotics. (PubMed, Front Psychiatry) - No abstract available

Adverse events • Journal • CNS Disorders

Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double-blind, randomized, placebo-controlled, Phase 3 clinical trial. (PubMed, Psychiatry Clin Neurosci) - "Zuranolone improved depressive symptoms on Day 15, compared with placebo, in Japanese patients with MDD. No new safety signals were observed."

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