Zurzuvae (zuranolone) / Sage Therapeutics, Shionogi, Biogen - LARVOL DELTA

Zuranolone in Palliative Care: Promise and Practicality for the Rapid Treatment of Depression. (PubMed, Am J Hosp Palliat Care) - "This paper will provide clinicians with an update on a new antidepressant with potential benefits for the palliative care population. The paper will review the pharmacology, pharmacodynamics, safety profile, and clinical studies showing its effectiveness in major depression and how it can potentially be helpful in the palliative care population."

Journal • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Palliative care • Psychiatry • Sleep Disorder

Assessing the utility of zuranolone to modify alcohol-related behaviours (CINP-AsCNP 2025) - "Zuranolone demonstrates sex-dependent effects on binge drinking and locomotor activity. Future research should explore potential benefits of neurosteroid treatments for AUD and their mechanism(s) of action, which may accelerate development of sex-specific treatments. Further, these findings underscore the importance of considering sex as a biological variable in the development of tailored, effective therapies for AUD."

Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Mental Retardation • Postpartum Depression • Psychiatry

Justice Delayed: The Case of Zuranolone and Barriers to Advancing Perinatal Mental Health. (PubMed, Psychiatr Serv) - "By discussing challenges in the development of and access to zuranolone, an innovative oral pharmacological treatment for postpartum depression, this Open Forum examines the systemic exclusion of women's mental health issues from research and advocacy efforts, highlighting how these gaps perpetuate injustice in the health care system. Issues such as inadequate funding for women's mental health research, insurance coverage limitations, and inequities in treatment accessibility represent systemic disparities that violate the foundational principle of justice in medical ethics."

Journal • CNS Disorders • Depression • Postpartum Depression • Psychiatry

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

AHA: Allopregnanolone in Post-Stroke Depression (clinicaltrials.gov) - P2 | N=6 | Not yet recruiting | Sponsor: Duke University | Initiation date: Apr 2025 ➔ Jul 2025

Trial initiation date • Cardiovascular • CNS Disorders • Depression • Mood Disorders • Psychiatry

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

The Emerging Role of Neurosteroids: Novel Drugs Brexanalone Sepranolone Zuranolone and Ganaxolone in Mood and Neurological Disorders (APA 2025) - "Description This review investigates the potential of neurosteroids, including brexanolone, zuranolone, sepranolone, and ganaxalone, as therapeutic agents for a range of mood and neurological disorders. Their modulation of the GABA system emerges as a central mechanism of action, emphasizing the importance of GABAergic signaling in these conditions. The path forward entails continued investigation and clinical trials to fully unlock the potential of neurosteroids, offering hope for enhanced treatments in these challenging clinical domains."

Alzheimer's Disease • CNS Disorders • Depression • Epilepsy • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry

Improvement in Anhedonia Symptoms With Zuranolone in Patients With Postpartum Depression (PPD): A Post Hoc Analysis of the Phase 3 Skylark Study (APA 2025) - P3 | "Treatment with zuranolone improved anhedonia in adults with PPD."

Clinical • P3 data • Retrospective data • Anesthesia • CNS Disorders • Depression • Mood Disorders • Postpartum Depression • Psychiatry • Sleep Disorder

Novel and Non-Pharmacologic Therapeutics for Perinatal Mood and Anxiety Disorders (APA 2025) - "By the conclusion of the session, participants will be able to counsel patients to help them make informed decisions about short-term pharmacotherapy and non-pharmacologic interventions for perinatal mood and anxiety disorders using up-to-date and evidence-based recommendations. Instructional Level Intermediate; Learning Objectives Objective One: To discuss evidence-based therapeutic and behavioral interventions for perinatal mood and anxiety disorders (PMADs) Objective Two: To assess the role of novel digital health interventions in perinatal mental health treatment plans Objective Three: To summarize the evidence base and safety of neuromodulation (ECT, TMS) in the peripartum Objective Four: To explain novel aspects of rapid-acting pharmacologic agents including brexanolone and zuranolone and emerging data surrounding peripartum ketamine use for PMADs Objective Five: To delineate a framework for discussing the risks and benefits of treatment options with perinatal..."

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

New Vistas in the Treatment of Mood and Anxiety Disorders: Psychedelics, Neuromodulation and More (APA 2025) - "The combination of dextromethorphan and bupropion was recently FDA approved for major depression, as was intranasal esketamine. Promising novel agents under scrutiny in clinical trials for depression include lumateperone, already approved for the treatment of schizophrenia and bipolar disorder, esmethadone, a non-mµ opiate receptor antagonist and more than one kappa opiate antagonist for the treatment of depression with prominent anhedonia, positive allosteric modulators of the GABA-A receptor for GAD and MDD (as a follow up to the approval of brexanolone and zuranolone for the treatment of post-partum depression), a novel agent that acts as a thyroid hormone receptor agonist for MDD, fasedienol for the treatment of social anxiety disorder, a novel intracellular modulator of MTORC1 in the treatment of depression, triple (DA, NE, 5HT) reuptake inhibitors for depression and an orexin antagonist for the treatment of depression. Instructional Level Intermediate;..."

Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Postpartum Depression • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia • Social Anxiety Disorder • Vascular Neurology

Zuranolone (Zurzuvae) for the Treatment of Postpartum Depression. (PubMed, Am Fam Physician) - No abstract available

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

Synthesis and Evaluation of a Novel Zuranolone Analog with High GABAA Receptor PAM Activity and Excellent Pharmacokinetic Profiles. (PubMed, Molecules) - "It also outperformed Zuranolone in pentylenetetrazole (PTZ)-induced seizure suppression and threshold dose for loss of righting reflex (LORR) in rats. The C21-pyridine-triazolone pharmacophore in S9 enhances receptor activity potency without increasing lipophilicity, optimizing pharmacokinetics and safety, which makes it a promising therapeutic candidate for depression and epilepsy."

Journal • PK/PD data • CNS Disorders • Depression • Epilepsy • Postpartum Depression • Psychiatry

A retrospective chart review study of patients treated in a hospital-based brexanolone program. (PubMed, Arch Womens Ment Health) - "While further research is needed, this study supports brexanolone as an efficacious treatment for PPD."

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

Comparative efficacy and safety of different pharmacological interventions for the treatment of depression associated with insomnia in the elderly population: a systematic review and network meta-analysis. (PubMed, Psychogeriatrics) - "All types of intervention were effective in decreased Insomnia Severity Index (ISI) and depression score, and sertraline had the highest probability of being the most effective intervention in decreasing the ISI (standard mean difference (SMD) = -2.17, 95% confidence interval (95% CI): -2.60, -1.75), Hamilton Depression Scale (HAM-D: SMD = -3.10, 95% CI: -3.60, -2.61) in elderly patients with depression and insomnia...In terms of the number of patients reporting escitalopram and zuranolone, zolpidem, seltorexant and eszopiclone had higher risks of serious adverse events than placebo or other treatments...Escitalopram, zuranolone, and seltorexant did not show overall material benefits in reducing ISI. These results should serve evidence-based clinical practice."

Journal • Retrospective data • Review • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Unveiling the potential biochemical effects of selected heterocyclic compounds as human Type-A γ-aminobutyric acid (GABA A) Modulator: An Insilico Approach. (PubMed, Biotechnol Rep (Amst)) - "Investigating the bioactivities of zuranolone derivatives as Type-A γ-aminobutyric acid inhibitors which will thereby down-regulate postpartum depression is considered a crucial study...Also, compound 1 and reference compound were subjected to molecular dynamic simulation study and the actual binding energy for the selected compounds were obtained and reported. Our findings from this work may open door for the design of several 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3-(benzyloxy)-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile derivatives as potential Type-A γ-aminobutyric acid inhibitors."

Journal • CNS Disorders • Depression • Postpartum Depression • Psychiatry

Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review. (PubMed, Medicina (Kaunas)) - " The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small...NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with..."

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

Racial and ethnic diversity in zuranolone and brexanolone clinical trials for postpartum depression: A cross-sectional analysis of ClinicalTrials.gov. (PubMed, Eur Neuropsychopharmacol) - No abstract available

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

Comment on the study "the efficacy and safety of zuranolone for treatment of depression: a systematic review and meta-analysis". (PubMed, Psychopharmacology (Berl)) - No abstract available

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

Pharmacology of novel, fast-acting, non-monoaminergic antidepressants (PubMed, Neuropsychopharmacol Hung) - "Two glutamatergic drugs, esketamine and dextromethorphan-bupropion (AXS-05), have already been approved for the treatment of treatment-resistant depression. The GABAergic drugs brexanolone and zuranolone are approved for the treatment of postpartum depression. These novel treatment options pave the way for novel avenues for further research and new targets in the treatment of depression. Keywords: depression, antidepressant, glutamate, fast-acting antidepressant, non- monoaminergic antidepressant."

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

New Directions in Neurosteroid Therapeutics in Neuropsychiatry. (PubMed, Neurosci Biobehav Rev) - "In recent years three neuroactive steroids (NAS), brexanolone (allopregnanolone, AlloP), ganaxolone and zuranolone, have been approved for the treatment of neuropsychiatric illnesses including postpartum depression and seizures in a neurodevelopmental syndrome. In this review, we explore GABAergic and other cellular effects of pregnane steroids including novel molecules that have potential therapeutic importance. This work discusses the complex chemical nature of NAS and what is being learned at cellular, molecular, synaptic and brain network levels about key sites of action including GABAARs and other targets."

Journal • Review • CNS Disorders • Depression • Epilepsy • Inflammation • Major Depressive Disorder • Mental Retardation • Postpartum Depression • Psychiatry

Zuranolone (Zurzuvae) for Treatment of Severe Postpartum Depression in Adults. (PubMed, Am Fam Physician) - No abstract available

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

Current evidence for the role of rapid-acting antidepressants (RAAD) in bipolar depression? A perspective and plan for action. (PubMed, Biol Psychiatry) - "The following RAAD substance classes have been or are currently investigated as possible treatments for bipolar depression: NMDA antagonists and indirect AMPA agonists (ketamine, esketamine, riluzole, felbamate), GABA-A activators or positive allosteric modulators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa-opioid receptor antagonists (navacaprant). Recent research into RAADs demonstrates the growing field of novel mechanisms of action in the pharmacological treatment of bipolar depression. However, there is an urgent need for well-controlled clinical studies on RAADs in bipolar depression to expand treatment options and improve outcomes for millions of affected individuals worldwide."

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

#Zuranolone: How TikTokers Perceive the First Available Oral Medication for Postpartum Depression. (PubMed, Arch Womens Ment Health) - No abstract available

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

Zuranolone for Postpartum Depression After Highly Lethal Suicide Attempt: Two Case Illustrations and a Narrative Literature Review. (PubMed, J Acad Consult Liaison Psychiatry) - "Postpartum suicidality is complex and often emerges rapidly. Our case series demonstrated that zuranolone may effectively treat PPD with rapid-onset highly lethal suicide attempts. We advocate for more research on fast-acting novel treatments, such as zuranolone and brexanolone, for PPD and postpartum suicidality."

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

FDA-Approved Zuranolone: First Oral Treatment for Postpartum Depression, Ushering in a New Era of Hope; A Narrative Review. (PubMed, Health Sci Rep) - "However, concerns regarding its safety for breastfeeding women and potential side effects necessitate further research and cautious use. Despite these challenges, zuranolone offers hope for improved outcomes and enhanced quality of life for individuals affected by PPD."

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