Publications by authors named "Stephen Kanes"
Article Synopsis
- - Major depressive disorder (MDD) can significantly impact a person's ability to function and traditional antidepressant treatments take weeks to show effects; zuranolone is a new oral treatment that's been approved for postpartum depression and is being studied for MDD.
- - The CORAL Study tested the effectiveness of zuranolone (50 mg) when combined with standard antidepressant therapy against a placebo in 425 adults with MDD, focusing on improvements in depression symptoms within the first three days.
- - Results showed that patients taking zuranolone experienced a greater reduction in depression scores by Day 3 compared to those on placebo, with mild to moderate side effects being the most common, such as drowsiness and headaches.
Article Synopsis
- * Patients in the zuranolone group experienced notable symptom relief as early as day 3, and this improvement was sustained through day 15 and beyond, with a statistically significant change from baseline scores.
- * The treatment was generally well tolerated, with similar rates of serious adverse events in both the zuranolone and placebo groups, suggesting its potential as a viable option for treating major depressive disorder.
A healthy stress response is critical for good mental and overall health and promotes neuronal growth and adaptation, but the intricately balanced biological mechanisms that facilitate a stress response can also result in predisposition to disease when that equilibrium is disrupted. The hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system plays a critical role in the body's response and adaptation to stress, and vasopressinergic regulation of the HPA axis is critical to maintaining system responsiveness during chronic stress. However, exposure to repeated or excessive physical or emotional stress or trauma can shift the body's stress response equilibrium to a "new normal" underpinned by enduring changes in HPA axis function.
View Article and Find Full Text PDFArticle Synopsis
- The MOUNTAIN study aimed to assess the effectiveness and safety of zuranolone, a new treatment for major depressive disorder (MDD), through a phase 3 trial involving adult outpatients.
- 581 participants were randomly assigned to receive either zuranolone (20 mg or 30 mg) or a placebo over 14 days, with improvements in depression symptoms measured primarily by the HDRS-17 scale.
- While the primary endpoint was not met, significant improvements in depressive symptoms were observed at days 3, 8, and 12 for the 30 mg zuranolone group, and the treatment was generally well tolerated with similar rates of side effects as the placebo group.
Article Synopsis
- Zuranolone, a treatment for postpartum depression (PPD), showed significant improvements in both anxiety and insomnia symptoms in women participating in a clinical study compared to a placebo.* -
- The study involved a double-blind, randomized trial with women aged 18-45 who had PPD, following treatment with either zuranolone or a placebo over a 14-day period.* -
- Results indicated higher rates of concurrent remission in depressive and anxiety symptoms with zuranolone, as well as positive effects on insomnia and overall functional health.*
Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program.
J Affect Disord
January 2023
Article Synopsis
- Brexanolone is the first FDA-approved treatment for postpartum depression (PPD), stemming from results of one Phase 2 and two Phase 3 clinical trials.
- In a pooled analysis of these trials, patients receiving brexanolone had faster and more significant reductions in depression, anxiety, and insomnia symptoms than those receiving a placebo.
- The findings reinforce brexanolone's effectiveness in improving PPD symptoms, although the study had limitations in assessing certain outcomes.
Article Synopsis
- Major depressive disorder (MDD) significantly impacts health-related quality of life (HRQoL), and this study examined how the neuroactive steroid zuranolone affects HRQoL using the Short Form-36v2 Health Survey (SF-36v2).
- Adult patients with MDD were randomly assigned to receive either zuranolone or a placebo for two weeks, with HRQoL assessed across various domains at Day 15 showing substantial improvements for those treated with zuranolone, particularly in areas like Mental Health and Vitality.
- The results suggest that zuranolone leads to rapid and meaningful HRQoL enhancements compared to placebo, although the small sample size may limit generalizability and other factors could influence HRQoL
Article Synopsis
- This study aimed to assess the effectiveness of two doses of zuranolone (30 mg and 45 mg) in improving sleep in a phase advance insomnia model compared to a placebo.
- In a double-blind crossover study, healthy adults were tested with three treatment periods and their sleep was measured using polysomnography and questionnaires.
- Results showed that zuranolone significantly improved sleep metrics like sleep efficiency, wake after sleep onset, and total sleep time, with the drug being well tolerated overall, primarily causing mild side effects like headache and fatigue.
Article Synopsis
- Postpartum depression (PPD) is a prevalent medical issue affecting mothers and their children, leading to the need for effective treatments.* -
- A phase 3 clinical trial tested zuranolone, a new drug, by comparing its effects to a placebo on women with PPD over a 2-week period.* -
- Results showed that zuranolone significantly reduced depression scores compared to placebo, indicating its potential efficacy and safety for treating PPD.*
Objective: To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity.
Methods: Patient data ( = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version.
Article Synopsis
- Parkinson's disease (PD) involves both motor and nonmotor symptoms, with tremor being difficult to treat, often not responsive to traditional dopamine therapy.
- An open-label study tested zuranolone, a new oral treatment, on 14 PD patients over 7 days, focusing on reducing tremor symptoms measured by the MDS-UPDRS score.
- Results showed a significant 40% improvement in tremor symptoms on Day 8 without serious side effects, with common mild adverse events including dizziness and sedation, suggesting zuranolone is a promising adjunct treatment for PD tremors.
Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up).
View Article and Find Full Text PDFThe objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms.
View Article and Find Full Text PDFPostpartum depression (PPD) is a unique subtype of major depressive disorder and a substantial contributor to maternal morbidity and mortality. In addition to affecting the mother, PPD can have short- and long-term consequences for the infant and partner. The precise etiology of PPD is unknown, but proposed mechanisms include altered regulation of stress response pathways, such as the hypothalamic-pituitary-adrenal axis, and dysfunctional gamma-aminobutyric acid (GABA) signaling, and functional linkages exist between these pathways.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the effectiveness and safety of SAGE-217, a GABA receptor modulator, for treating major depressive disorder compared to a placebo.
- In a double-blind trial, 89 patients received either SAGE-217 or placebo, with the main focus on changes in depression severity after 15 days, measured by the Hamilton Depression Rating Scale (HAM-D).
- Results showed a significant improvement in the SAGE-217 group, with greater reductions in HAM-D scores and no serious side effects reported, though some common mild side effects like headache and dizziness occurred.
Article Synopsis
- SAGE-217 is a new drug designed to modulate GABA receptors and was tested in phase I studies to evaluate its safety and how it behaves in the body (pharmacokinetics) after being taken orally.
- In these studies, 108 healthy volunteers participated, where doses ranged from 0.25 to 66 mg for single doses and 15 to 35 mg for multiple daily doses over a week; the drug was mostly well tolerated with mild side effects.
- The drug's pharmacokinetics showed it has a half-life of 16-23 hours, and after successful results, SAGE-217 is moving on to phase II studies for treating major depressive disorder
Background: Post-partum depression is associated with substantial morbidity, and improved pharmacological treatment options are urgently needed. We assessed brexanolone injection (formerly SAGE-547 injection), a positive allosteric modulator of γ-aminobutyric-acid type A (GABA) receptors, for the treatment of moderate to severe post-partum depression.
Methods: We did two double-blind, randomised, placebo-controlled, phase 3 trials, at 30 clinical research centres and specialised psychiatric units in the USA.
Objective: Super-refractory status epilepticus (SRSE) is a life-threatening form of status epilepticus that continues or recurs despite 24 hours or more of anesthetic treatment. We conducted a multicenter, phase 1/2 study in SRSE patients to evaluate the safety and tolerability of brexanolone (USAN; formerly SAGE-547 Injection), a proprietary, aqueous formulation of the neuroactive steroid, allopregnanolone. Secondary objectives included pharmacokinetic assessment and open-label evaluation of brexanolone response during and after anesthetic third-line agent (TLA) weaning.
View Article and Find Full Text PDFBackground: Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABA) receptors, for the treatment of post-partum depression.
Methods: For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA.
Objective: Preclinical evidence indicates that rapid changes in levels of allopregnanolone, the predominant metabolite of progesterone, confer dramatic behavioral changes and may trigger postpartum depression (PPD) in some women. Considering the pathophysiology of PPD (i.e.
View Article and Find Full Text PDFObjective: To provide an estimate of the annual number of super-refractory status epilepticus (SRSE) cases in the US and to evaluate utilization of hospital resources by these patients.
Methods: The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.
Background: AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor that is rapidly metabolized to an inactive metabolite by esterases present in blood and liver. Preclinical results suggest that AZD3043 has the potential as a short-acting IV sedative/anesthetic drug with rapid and predictable recovery characteristics and a favorable safety and tolerability profile.
Methods: Our primary objective in this phase 1, single-center, open-label study was to evaluate the safety and tolerability of AZD3043 after IV infusion and to estimate the maximal tolerated dose.