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

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

IV Allo PTSD: Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD. (clinicaltrials.gov) - P2 | N=96 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

IV Allo PTSD: Facilitation of Extinction Retention and Reconsolidation Blockade by IV Allopregnanolone in PTSD. (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Neurosteroids Progesterone and Dehydroepiandrosterone: Molecular Mechanisms of Action in Neuroprotection and Neuroinflammation. (PubMed, Pharmaceuticals (Basel)) - "However, only the allopregnanolone analogs brexanolone and zuranolone have been recently approved by the FDA for the treatment of depression. The aspects of their participation in these pathological processes are discussed. New formulations, such as lipophilic emulsions, nanogels, and microneedle array patches, are attractive strategies to overcome the low bioavailability of these neurosteroids for the amelioration and treatment of various nervous disorders."

Journal • Review • CNS Disorders • Depression • Epilepsy • Fragile X Syndrome • Genetic Disorders • Inflammation • Psychiatry • Vascular Neurology • BCL2

Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression-Focus on Zuranolone. (PubMed, Int J Mol Sci) - "The first rapid-acting neurosteroid approved by the FDA to treat PPD in women is brexanolone, although its use is constrained by pharmacokinetic properties. The first oral neuroactive steroid-based antidepressant approved by the FDA for PPD is zuranolone. This review discusses the molecular mechanism of zuranolone action and the results of preclinical and clinical studies regarding the effectiveness and safety of the drug in treating PPD."

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

A Study to Assess the Safety and Efficacy of Oral LPCN 1154A in Women With Severe PPD (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Lipocine Inc. | Not yet recruiting ➔ Recruiting

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

Brexanolone, zuranolone and related neurosteroid GABAA receptor positive allosteric modulators for postnatal depression. (PubMed, Cochrane Database Syst Rev) - "This review provides moderate-certainty evidence that zuranolone probably improves depression response and remission but also increases maternal adverse events compared to placebo. There may be little or no difference in depression response and remission and probably little or no difference in maternal adverse events with intravenous neurosteroid GABAA positive allosteric modulators such as brexanolone, compared to placebo. Evidence from this review, alongside current clinical guidelines and reference to evidence from the general adult population, could be used to inform an individualised risk-benefit discussion with women seeking treatment for postnatal depression. However, it is difficult to make recommendations about the use of neurosteroid GABAA receptor positive allosteric modulators for the treatment of postnatal depression as no studies have compared them to active treatment."

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

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 | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: Apr 2025 ➔ Aug 2025

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

Neurosteroid treatment of postpartum depression and beyond. (PubMed, Br J Psychiatry) - "Depression occurring during pregnancy or after delivery is one of the most common complications of childbirth and is associated with maternal morbidity and mortality. Here we review the breakthrough development of the first neuroactive steroid-based antidepressants approved for postpartum depression in the USA and their potential in other psychiatric illnesses."

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

Brexanolone 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 | Initiation date: Apr 2025 ➔ Jul 2025

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

New Agents in the Treatment of Psychiatric Disorders: What Innovations and in What Areas of Psychopathology? (PubMed, Pharmaceuticals (Basel)) - "Our search suggested that a new antipsychotic, lumateperone, and two drug combinations, olanzapine/samidorphan (OLZ/SAM) and xanomeline/trospium (KarXT), were approved for schizophrenia...Two new agents, brexanolone and zuranolone, were approved for treatment of postpartum depression...In summary, some new psychotropic medications have been developed, in particular with the aim to improve the symptoms of resistant patients and to decrease the incidence of adverse effects. It is necessary to continue testing the effectiveness of new compounds in methodologically rigorous studies."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Obsessive-Compulsive Disorder • Postpartum Depression • Psychiatry • Schizophrenia • Suicidal Ideation