- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: Treating Postpartum Depression: What Do We Know about Brexanolone? (Pubmed Central) - Jul 22, 2021
A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone's use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a 'breakthrough' in managing PPD, and review the cost-related barriers to its worldwide standardized use.
- |||||||||| Zolgensma (onasemnogene abeparvovec-xioi) / Novartis, Zulresso (brexanolone) / Sage Therapeutics, Mayzent (siponimod) / Novartis
Journal: Siponimod, onasemnogene abeparvovec-xioi, and brexanolone. (Pubmed Central) - Jun 30, 2021
Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a 'breakthrough' in managing PPD, and review the cost-related barriers to its worldwide standardized use. No abstract available
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Evaluating Brexanolone for the Treatment of Postpartum Depression. (Pubmed Central) - Jun 26, 2021
It is appropriate for use in women with moderate to severe PPD. Experience with the medication and further research is needed to clarify whether the current recommended dosing regimen is required for efficacy.
- |||||||||| ketamine / Generic mfg.
Journal: Transdermal delivery of breakthrough therapeutics for the management of treatment-resistant and post-partum depression. (Pubmed Central) - Jun 22, 2021
For the first time in over three decades, the year 2019 saw the approval of two new classes of antidepressants: Spravato™ esketamine intranasal spray for treatment-resistant depression, and Zulresso® brexanolone infusion against post-partum depression...However, delivery of their high therapeutic doses (0.5 mg/kg ketamine in 1 h; 90 µg/kg/h brexanolone over 52 h) is unachievable by conventional means...The developed microemulsions resulted in significantly higher transdermal delivery across laser-treated skin. Although brexanolone demonstrated higher solubility in the w/o microemulsion (21.31 ± 0.14 mg/mL) than the o/w microemulsion (10.69 ± 0.09 mg/mL), percutaneous absorption from the o/w microemulsion (6.04 ± 0.16%) was significantly higher than the w/o microemulsion (1.92 ± 0.02%).
- |||||||||| dexamethasone / Generic mfg.
Review, Journal: The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD. (Pubmed Central) - Jun 22, 2021
Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.
- |||||||||| ganaxolone oral (CCD-1042) / Marinus
Review, Journal: Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders. (Pubmed Central) - Jun 16, 2021
We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.
- |||||||||| ganaxolone oral (CCD-1042) / Marinus
Clinical, Journal: Extra-synaptic modulation of GABA and efficacy in bipolar disorder. (Pubmed Central) - May 15, 2021
Brexanolone has been approved for the treatment of postpartum depression, ganaxolone is being studied for treatment-resistant depression, and gaboxadol development for the treatment of insomnia has been abandoned due to narrow therapeutic index. In addition to the current studies, these agents are expected to have particular efficacy in acute and prophylactic management of bipolar I disorder by hyperpolarizing the resting potential of neurons and antagonizing one of the most reproducible demonstrated biologic abnormalities of this illness.
- |||||||||| ketamine / Generic mfg.
Journal: Perinatal depression. (Pubmed Central) - May 4, 2021
Clinical monitoring and timely treatment of depression in the perinatal and postpartum periods is critical for maternal postpartum health and recovery. Perinatal specialists and researchers should continue to focus on tailored treatments specific to this special population.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] Brexanolone for Postpartum Depression: A Systematic Review () - May 2, 2021 - Abstract #APA2021APA_1249;
These results were measured primarily by changes in HAM-D scales to assess symptoms of depression and by subjective reports of symptomatic improvements. Given the prevalence of postpartum depression, these results are promising for clinicians seeking effective treatment modalities.
- |||||||||| ketamine / Generic mfg.
[VIRTUAL] *Overcoming Barriers to the Implementation of Novel Treatments for Mood Disorders () - Apr 13, 2021 - Abstract #ASCP2021ASCP_170;
For example, the Food and Drug Administration (FDA) recently approved new therapies (esketamine, brexanolone) for mood disorders that have novel mechanisms of action and different routes of administration compared with traditional antidepressant drugs...Samuel T. Wilkinson (Yale) will speak on overall barriers to interventional psychiatry treatments, including electroconvulsive therapy, racemic ketamine, and esketamine nasal spray...Learning Objectives 1) To be able to describe the potential barriers to implementing new treatment / pharmacologic approaches to depression that have different routes of administration compared to standard antidepressants. 2) To be able to describe potential solutions to overcoming barriers to the implementation of these treatments
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] Perceptions and Efficacy of Brexanolone for the Treatment of Postpartum Depression: A Mixed Methods Analysis () - Apr 4, 2021 - Abstract #CPNP2021CPNP_217;
Outcomes: Through semi-structured interviews, we hope to generate rich qualitative data that informs the design of a quantitative instrument to further assess intention to utilize BRX for the treatment of PPD. The primary outcome measure for our retrospective review will be a change in the Edinburgh Postnatal Depression Scale (EDPS) before, during, and after infusion with BRX.
- |||||||||| sirolimus / Generic mfg.
Review, Journal: A hypothesis of monoamine (5-HT) - Glutamate/GABA long neural circuit: Aiming for fast-onset antidepressant discovery. (Pubmed Central) - Mar 23, 2021
In 2019, the launch of fast-acting antidepressants such as S-ketamine(S-Ket) and brexanolone into market by FDA has opened up new prospects for non-monoamine strategy mainly based on the N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid type A (GABA) receptors...Therefore, five potential strategies are proposed for fast-acting antidepressant based on this circuit: 1) Achieve the rapid E/I balance by relieving the inhibition of GABA interneurons on glutamatergic pyramidal neurons or directly activating pyramidal neurons; 2) Simultaneously modulate 5-HT neuronal activity and Glu/GABA balance by 5-HT transporter combining with some receptors such as 5-HT (namely simultaneous enhancement of the 5-HT and Glu/GABA links); 3) Directly activate mammalian rapamycin target protein complex 1 (mTORC1) and rapidly enhance brain-derived neurotrophic factor (BDNF) -mTOR pathway; 4) Stimulate rapid release of BDNF in the brain; 5) Positive allosteric modulator of synaptic and extrasynaptic GABA receptors. It is hoped that these ideas will provide possible strategies for the further development of a new generation of antidepressants and provide a useful reference for the further discovery of fast-onset antidepressant candidate targets.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] 9151 At the Interface of Science and Society: Integrating Neuroscience Into Modern Psychiatry () - Mar 8, 2021 - Abstract #APA2021APA_32;
New research is already translating into a range of immediate clinical applications: from improved diagnostic tests (e.g. via chromosomal microarray testing for Autism Spectrum Disorders) to new medications (e.g. brexanolone for post-partum depression) and interventional approaches (e.g. deep brain stimulation for obsessive-compulsive disorder)...In this session we will briefly review findings that highlight the importance of integrating a neuroscience perspective into modern clinical care. We will then offer an individualized educational activity that illustrates a contemporary approach to online learning and introduces a framework for ongoing engagement with cutting-edge neuroscience.
- |||||||||| progesterone / Generic mfg.
Journal: Progesterone loading as a strategy for treating postpartum depression. (Pubmed Central) - Jan 30, 2021
However, studies of progesterone's effects in women suffering from PPD are few and inconclusive. We hypothesize that orally dosed progesterone will increase concentrations of allopregnanolone in the central nervous system, which should relieve symptoms of PPD.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, allopregnanolone (LJPC-0712) / La Jolla Pharma
Review, Journal: Postpartum Depression: Identification and Treatment in the Clinic Setting. (Pubmed Central) - Jan 15, 2021
Fortunately, there have been a variety of treatment studies using antidepressants, nonpharmacologic interactions, and most recently, allopregnanolone (Brexanolone) infusion that have shown benefits. The most commonly used screening scale, Edinburgh Postnatal Depression Scale, a 10-item self-rated scale, has been translated into a variety of languages.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Brexanolone Therapy for Postpartum Depression. (Pubmed Central) - Dec 17, 2020
Although there are several antidepressants currently used to treat PPD, they have not yet been approved by the FDA. No abstract available
- |||||||||| allopregnanolone (LJPC-0712) / La Jolla Pharma
[VIRTUAL] Antiseizure activity of intravenous bolus allopregnanolone in mice and rats () - Nov 28, 2020 - Abstract #AES2020AES_389;
However, the antiseizure effects diminish quickly. To the extent that Cmax (rather than extended exposure) is the critical parameter for acute seizure termination, IV bolus administration of allopregnanolone has potential as a rapidly acting medical intervention for the treatment of seizures and status epilepticus.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used? (Pubmed Central) - Nov 25, 2020
Brexanolone is an intravenous proprietary formulation of allopregnanolone that can be administered to produce stable serum levels comparable with third-trimester concentrations in postpartum mothers...In this review, we will highlight the results of the clinical trial program, including efficacy and tolerability data. Practical and logistical considerations of brexanolone will be reviewed, as will its potential place in therapy for the treatment of postpartum depression.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Brexanolone for postpartum depression. (Pubmed Central) - Nov 12, 2020
With a rapid onset of action, brexanolone could be considered advantageous over traditional therapies for PPD in patients for whom a rapid response is required due to severity of disease. Significant concerns remain regarding sustained effect and use in patients outside of the clinical trial setting.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Advances in treatment for postpartum major depressive disorder. (Pubmed Central) - Oct 21, 2020
To date, only one treatment (Brexanolone) has undergone registrational trials and is approved in the United States with an indication for the treatment of PPD...Large, randomized, controlled trials of hormonal treatments in patients with PPD are warranted. Also, treatment with mood stabilizers and/or antipsychotics in women with major depressive disorder, who meet the DSM-5 mixed features specifiers in the post-partum period, should be tested in controlled clinical trials.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] New Approaches to Modulate Forebrain Interneurons for the Treatment of Psychiatric Disease - Chair () - Sep 30, 2020 - Abstract #ACNP2020ACNP_846;
The results described in these translational talks have implications across multiple levels of drug development. Positive allosteric modulators for mGlu1 receptors are in active early-stage development, several classes of subtype-specific GABA receptor modulators are in ongoing clinical trials, and allopregnenalone (brexanolone) received FDA approval last summer as a Breakthrough Therapy for postpartum depression.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] New Approaches to Modulate Forebrain Interneurons for the Treatment of Psychiatric Disease () - Sep 30, 2020 - Abstract #ACNP2020ACNP_684;
The results described in these translational talks have implications across multiple levels of drug development. Positive allosteric modulators for mGlu1 receptors are in active early-stage development, several classes of subtype-specific GABA receptor modulators are in ongoing clinical trials, and allopregnenalone (brexanolone) received FDA approval last summer as a Breakthrough Therapy for postpartum depression.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] Insomnia Symptom Response in Patients With Postpartum Depression Treated With the Neuroactive Steroid Brexanolone Injection () - Sep 30, 2020 - Abstract #ACNP2020ACNP_572;
BRX treatment in women with PPD has previously been shown to provide rapid (Hour 24, HAMD-17 and Bech-6) and sustained improvement in depressive symptoms (all time points measured to Day 30, HAMD-17 and Bech-6) compared with placebo. In addition to its effects on core symptoms of depression in this trial, these post hoc analyses showed that BRX treatment also resulted in significantly greater reductions in insomnia-related symptoms and higher proportions of patients achieving an insomnia-related symptom response compared with placebo (as measured by the HAMD-17-Ins subscale).
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
[VIRTUAL] Anxiety Symptom Response in Patients With Postpartum Depression Treated With the Neuroactive Steroid Brexanolone Injection () - Sep 30, 2020 - Abstract #ACNP2020ACNP_103;
BRX treatment in women with PPD has previously been shown to provide rapid (Hour 24 for HAMD-17 total score and Bech-6 score) and sustained improvement in depressive symptoms (HAMD-17 total score and Bech-6 score at all subsequent measured time points up to Day 30) compared with placebo. In addition to its effects on core symptoms of depression in this trial, these post hoc analyses showed that BRX treatment also resulted in significantly greater reductions in anxiety-somatization symptoms and higher proportions of patients who achieved an anxiety-somatization symptom response compared with placebo (as measured by the HAMD-17-A/S subscale).
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Brexanolone For Postpartum Depression: A Novel Approach and a Call for Comprehensive Postpartum Care. (Pubmed Central) - Sep 22, 2020
The efficacy data surrounding brexanolone are encouraging; there is also evidence, however, that postpartum depression may be mitigated by a number of social policies that provide support to new parents. We suggest a comprehensive approach to postpartum wellness that includes investing in evidence-based social interventions that may be much more accessible to the millions of Americans experiencing postpartum mood disturbance.
- |||||||||| Clinical, Journal: Keeping up with the clinical advances: depression. (Pubmed Central) - Aug 4, 2020
Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Clinical, Journal: Brexanolone for Postpartum Depression: Clinical Evidence and Practical Considerations. (Pubmed Central) - Jul 29, 2020
Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of over sedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, ganaxolone oral (CCD-1042) / Marinus
Journal: Isobolographic Analysis of Antiseizure Activity of the GABA-A Receptor-Modulating Synthetic Neurosteroids Brexanolone and Ganaxolone with Tiagabine and Midazolam. (Pubmed Central) - Jul 7, 2020
SIGNIFICANCE STATEMENT: This paper investigates for the first time the potential synergistic interactions between two neurosteroids with anticonvulsant properties, allopregnanolone (brexanolone) and the very similar synthetic analog, ganaxolone, and two conventional antiepileptic drugs active at GABA-A receptors, the GABA reuptake inhibitor, tiagabine, and a benzodiazepine, midazolam. The results demonstrate a synergistic protective effect of neurosteroid-tiagabine combinations, as well as neurosteroid-midazolam regimens in seizure models.
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