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

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

A Study to Assess the Safety and Efficacy of Oral LPCN 1154A in Women With Severe PPD (clinicaltrials.gov) - P3 | N=90 | Completed | Sponsor: Lipocine Inc. | Recruiting ➔ Completed

Trial completion • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry

Advances in antidepressant pharmacotherapy: phase 3 evidence and clinical perspectives. (PubMed, Expert Opin Pharmacother) - "Data on efficacy, safety, and relapse prevention from pivotal trials of brexanolone, intranasal esketamine, dextromethorphan - bupropion, vortioxetine, and metabolism-based interventions such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are discussed. However, limited guideline integration, insufficient long-term data, and implementation barriers restrict their clinical uptake. Clearer sequencing strategies and harmonized recommendations are needed to support more individualized depression management."

Journal • P3 data • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry • Suicidal Ideation

Intravenous Brexanolone for the Treatment of Posttraumatic Stress Disorder: A Case Report. (PubMed, Am J Psychiatry) - No abstract available

Journal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Brexanolone infusion produces sustained anti-inflammatory and neurotrophic effects in patients with postpartum depression that predict symptom improvement. (PubMed, Transl Psychiatry) - "Biomarker × time interactions suggested dynamic regulation of inflammatory and neurotrophic pathways. Given the small sample size, these findings should be interpreted as a pilot study, but they indicate that brexanolone promotes both rapid and sustained anti-inflammatory and neurotrophic effects supporting lasting symptom remission in PPD."

Journal • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry • BDNF • CCL11 • CCL4 • CXCL8 • HMGB1 • IL18 • IL1B • IL6 • TLR4 • TNFA

Study on Allopregnanolone and Depression in Perimenopausal Women (clinicaltrials.gov) - P4 | N=2 | Terminated | Sponsor: Brigham and Women's Hospital | N=80 ➔ 2 | Recruiting ➔ Terminated; low enrollment

Enrollment change • Trial termination • CNS Disorders • Depression • Mood Disorders • 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

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

An open-label, proof-of-mechanism trial evaluating a neuroactive steroid GABA modulator in tinnitus. (PubMed, Front Neurol) - P2 | "This pilot, single-arm, proof-of-mechanism trial investigated whether brexanolone, an intravenous formulation of allopregnanolone, may improve tinnitus symptomatology...Further evaluation in randomized placebo-controlled trials is needed to confirm these findings. The study was registered on September 21, 2024, with the identifier number NCT05645432."

Clinical • Journal • Otorhinolaryngology

Molecular mechanisms of neurosteroids in temporal lobe epilepsy: current insights and therapeutic perspectives. (PubMed, Mol Biol Rep) - "Neurosteroids (NSs) are endogenous progesterone derivatives that act as natural allosteric modulators of GABAA ​receptors, exerting distinct effects from conventional receptor agonists...Accumulating evidence indicates that NSs, including Allopregnanolone, brexanolone, and ganaxolone, may exert neuroprotective and anti-epileptogenic effects through both direct GABAergic modulation and indirect regulation of mTORC1, AMPK, and BDNF signaling pathways, as well as autophagy activation...This review synthesizes current knowledge on the mechanistic roles of NSs in TLE, highlighting their potential as adjuvant therapies alongside antiepileptic drugs. Further translational studies are warranted to clarify optimal dosing strategies, identify patient subgroups most likely to benefit, and develop targeted NS analogues for refractory TLE management."

Journal • Review • CNS Disorders • Epilepsy • Inflammation

Open-label study of the efficacy, safety and tolerability of Brexanolone in the treatment of adult women with postpartum psychosis. (PubMed, Gen Hosp Psychiatry) - "This study suggests the potential for neuroactive steroids as rapid-acting, adjunctive treatment for PPP and provides support for future research to assess the role of neuroactive steroids and synthetic forms of allopregnanolone in the treatment of PPP."

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

AN ELUSIVE CASE OF SUPER REFRACTORY STATUS EPILEPTICUS (CHEST 2025) - "His seizures were uncontrolled despite high doses of propofol (70 mcg/kg/min), and other AEDs were also added incrementally (levetiracetam 2 g twice daily, lacosamide 200 mg twice daily, valproic acid 500 mg every 6 hours, topiramate 200 mg every 12 hours, phenobarbital 130 mg daily, perampanel 16 mg daily (after a loading dose of 24 mg)...We also performed plasmapheresis (every other day for 5 times), pulse dose steroids (1 g intravenous methylprednisolone for 5 days) till auto-immune and paraneoplastic workup came back as negative...Commonly used IVAs include midazolam, pentobarbital, and propofol, with alternatives being ketamine, isoflurane, desflurane and brexanolone. Commonly used AEDs are phenobarbital, phenytoin, fosphenytoin, levetiracetam, valproate, and lacosamide, while some of the newer ones include brivaracetam, clobazam, and rufinamide... SRSE is a complex clinical condition requiring further research to establish optimal management tactics. Our patient..."

Clinical • Addiction (Opioid and Alcohol) • Aesthetic Medicine • Anesthesia • Epilepsy • Immunology • Infectious Disease • Pneumonia • Respiratory Diseases • Septic Shock • Vascular Neurology

Real-World Outcomes of Brexanolone to Treat Postpartum Depression. (PubMed, Womens Health Rep (New Rochelle)) - "Importantly, 15 participants had a diagnosis of bipolar depression and were prescribed an antipsychotic or mood stabilizer at the time of treatment, there were no episodes of mania or hypomania reported during the follow-up period. Given the shared mechanism of action between brexanolone and the recently approved oral medication for PPD, zuranolone, the applicability of findings and relevance to the more accessible oral drug, zuranolone, are explored."

Journal • Real-world evidence • Bipolar Disorder • CNS Disorders • Depression • Long-acting Reversible Contraceptives • Mood Disorders • Postpartum Depression • Psychiatry

Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice. (PubMed, Clin Psychopharmacol Neurosci) - "Two rapid-acting therapeutic classes, NMDA receptor modulators (ketamine, esketamine) and neuroactive-steroid GABA-A positive allosteric modulators (brexanolone, zuranolone), offer complementary approaches to restore circuit function. Robust efficacy/tolerability predictors remain limited, though early symptomatic change is clinically informative. In conclusion, NMDA receptor modulators and neuroactive-steroid GABA-A positive allosteric modulators have improved the treatment for mood disorders and accelerated a transition to mechanism-driven care."

Journal • Review • Anesthesia • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry • Suicidal Ideation

Utility of Brexanolone to Target Stress-induced Alcohol Use Among Men and Women With Posttraumatic Stress Disorder (clinicaltrials.gov) - P1 | N=25 | Active, not recruiting | Sponsor: Yale University | Trial completion date: Aug 2025 ➔ Dec 2025 | Trial primary completion date: Aug 2025 ➔ Dec 2025

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

Navigating Therapies, Challenges, and Recommendations for Treatment-Resistant Peripartum Depression: A Comprehensive Review. (PubMed, Healthcare (Basel)) - "According to related research, pharmacological treatments such as SSRIs or brexanolone and zuranolone can be effective in addressing TRPD challenges, but they carry concerns regarding fetal and neonatal risk. Our findings imply that innovative therapeutics and integration of these interventions personalized to individual needs are the optimal clinical approach that may help in balancing maternal symptom control and perinatal safety. Also, expanded mental health infrastructure with enhanced research is essential for advancing TRPD care."

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

Brexanolone therapy in postpartum depression: a comprehensive review (ECNP 2025) - "The rapid onset of action exhibited by brexanolone confers a distinct advantage over conventional therapies for patients experiencing postpartum depression, particularly those necessitating immediate intervention due to the severity of their condition. This characteristic feature positions brexanolone as an important alternative, especially in instances where traditional treatments may not offer a total relief. In conclusion, the results from this study provide the evidence that brexanolone may be used in clinical practice for women with postpartum depression."

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

Two heartbeats, one molecule: The role of zuranolone in postpartum depression (ECNP 2025) - "It has emerged as an alternative to brexanolone – an earlier neuroactive steroid with a similar GABA-A receptor modulation which requires continuous intravenous infusion over a 60-hour period [3]. Zuranolone appears to be a promising approach in the treatment of PPD, given the evidence of its efficacy, short treatment duration, and rapid onset of action compared to conventional antidepressants, particularly selective serotonin reuptake inhibitors. These features may enhance accessibility and help overcome barriers to treatment adherence in the postpartum population. Nevertheless, further studies are required to fully evaluate its long-term safety profile—particularly in breastfed children of women taking zuranolone—and to determine the durability of its therapeutic effects."

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

Zuranolone and Brexanolone for the Treatment of Postpartum Depression. (PubMed, Obstet Gynecol) - "This document is a focused update of related content in Clinical Practice Guideline No. 5, Treatment and Management of Mental Health Conditions During Pregnancy and Postpartum (Obstet Gynecol 2023;141:1262-88) and replaces the August 2023 Practice Advisory, Zuranolone for the Treatment of Postpartum Depression."

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

Peripartum Depression Pharmacotherapies Targeting GABA-Glutamate Neurotransmission. (PubMed, J Clin Med) - "Search criteria targeted randomized clinical trials investigating GABA-A-positive allosteric modulators (brexanolone, zuranolone, and ganaxolone) and NMDA receptor antagonists (ketamine and esketamine) in PPD patients. These glutamate-GABA pathway modulators represent novel therapeutic alternatives with rapid onset profiles. Further investigation and research are needed to optimize dosing protocols and patient selection criteria and to establish long-term efficacy before PPD treatment guidelines can be drafted."

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

Epidemiology, pathophysiology, and interventions for postpartum depression: Systematic review. (PubMed, World J Clin Cases) - "Effective PPD management requires integrative, culturally sensitive approaches, prioritizing scalable, personalized non-pharmacological interventions to reduce disparities and enhance maternal mental health equity across diverse populations."

Journal • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Postpartum Depression • Psychiatry • CRP • IL6

Post marketing safety assessment of the novel postpartum depression drug, Zuranolone: evidence from real-world pharmacovigilance analysis based on the FDA adverse event reporting system. (PubMed, Front Psychiatry) - "Compared to Brexanolone, Zuranolone's adverse reactions were more focused on nervous system diseases, while the latter was primarily associated with psychiatric disorders, General disorders and administration site conditions, and Injury, poisoning and procedural complications. This study revealed potential AEs of Zuranolone, confirming known safety information about Zuranolone, providing comprehensive data for medical practice and public health decision-making, and laying the foundation for further clinical research. It also provides more comprehensive and updated evidence for the clinical safety of Zuranolone."

Adverse events • Journal • P4 data • Real-world evidence • Anesthesia • CNS Disorders • Depression • Fatigue • Insomnia • Mental Retardation • Migraine • Movement Disorders • Otorhinolaryngology • Pain • Postpartum Depression • Psychiatry • Sleep Disorder • Suicidal Ideation • Vertigo

New and emerging pharmacologic treatments for MDD. (PubMed, Front Psychiatry) - "Furthermore, the combination of dextromethorphan and bupropion has shown promise. Brexanolone, administered via infusion, and zuranolone, available as an oral formulation, both have demonstrated efficacy in clinical settings. Novel treatments targeting opioid pathways, such as esmethadone, and selective kappa receptor antagonists offer new hope for addressing the symptoms of MDD through mechanisms not traditionally associated with antidepressant action."

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