- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, Zurzuvae (zuranolone) / Sage Therapeutics, Shionogi, Biogen
Review, Journal: Current pharmacotherapy approaches and novel GABAergic antidepressant development in postpartum depression. (Pubmed Central) - Oct 9, 2023
Novel antidepressant development with allopregnanolone analogues, in contrast, has proven a promising avenue for the development of rationally designed and efficacious treatments. This state-of-the-art review presents the evidence for the current standard-of-care pharmacotherapy, hormonal treatment, and emerging allopregnanolone analogues for the treatment of postpartum depression along with a discussion of the current understanding of its neuroactive steroid-driven pathophysiology.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Trial completion date, Trial primary completion date: An Open-Label Study Evaluating Brexanolone in Adults With Tinnitus (clinicaltrials.gov) - Oct 2, 2023
P2, N=24, Recruiting,
This state-of-the-art review presents the evidence for the current standard-of-care pharmacotherapy, hormonal treatment, and emerging allopregnanolone analogues for the treatment of postpartum depression along with a discussion of the current understanding of its neuroactive steroid-driven pathophysiology. Trial completion date: Oct 2023 --> Apr 2024 | Trial primary completion date: Sep 2023 --> Apr 2024
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, Zurzuvae (zuranolone) / Sage Therapeutics, Shionogi, Biogen
Review, Journal: Exploring Novel Therapeutic Approaches for Depressive Disorders: The Role of Allopregnanolone Agonists. (Pubmed Central) - Sep 25, 2023
Brexanolone was approved by the FDA in 2019 for the treatment of postpartum depression and has greatly influenced further research into potential drugs such as zuranolone, which is currently undergoing phase 3 of clinical trials. Although these drugs exhibit improvement in symptoms of depressive disorders along with notable side effects, further research is required for their future clinical use.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, Zurzuvae (zuranolone) / Sage Therapeutics, Shionogi, Biogen
Journal: Have Effective Antidepressants Finally Arrived? Developments in Major Depressive Disorder Therapy. (Pubmed Central) - Aug 20, 2023
After nearly 50 years of legal injunctions against their use, psychedelic drugs have attracted interest among researchers seeking alternative antidepressants. Psilocybin, derived from mushrooms, remains under investigation for its benefits in treatment-resistant depression.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: GABA receptors as targets for treating affective and cognitive symptoms of depression. (Pubmed Central) - Aug 14, 2023
This review focuses on the GABA receptor (GABAR) system as a target for novel antidepressants and discusses the mechanisms by which modulation of ?-containing GABARs with neuroactive steroids (NASs) or of ?5-containing GABARs results in antidepressant or antidepressant-like actions and discusses clinical data on NASs. Moreover, a potential mechanism by which ?5-GABAR-positive allosteric modulators (PAMs) may improve cognitive deficits in depression is presented.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: Neurosteroid Influence on Affective Tone. (Pubmed Central) - Aug 9, 2023
Overall, approval of BX is a major milestone in the field of neurotherapeutics, paving the way for the development of novel synthetic neurosteroids to treat depression, epilepsy, and status epilepticus. The recent FDA-approval of a novel antidepressant treatment, ZULRESSO
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Divergent Transcriptomic Effects of Allopregnanolone in Postpartum Depression. (Pubmed Central) - Jul 2, 2023
Brexanolone, a formulation of the neurosteroid allopregnanolone (ALLO), is approved for treating postpartum depression (PPD) and is being investigated for therapeutic efficacy across numerous neuropsychiatric disorders...Likewise, the gene ontologies underlying ALLO-induced DEGs in PPD and Control LCLs were divergent. These data suggest that ALLO may activate unique and opposing molecular pathways in women with PPD, which may be tied to its antidepressant mechanism.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: Recent Developments in Pharmacotherapy of Depression: Bench to Bedside. (Pubmed Central) - May 27, 2023
More recently, the approval of a positive allosteric modulator of GABA-A receptors, brexanolone, has added to the list of recent breakthroughs with the relatively rapid onset of antidepressant efficacy...This narrative review aims to analyze the clinical pharmacology of recently approved antidepressants and discuss potential barriers to the bench-to-bedside transfer of knowledge and clinical application of exciting recent discoveries. Overall, clinically meaningful advances in the treatment of depression have not reached a large proportion of depressed patients, including those with treatment-resistant depression, who might benefit the most from the novel antidepressants.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Novel Drug Treatments for Psychiatric Disorders (Room 157, Moscone South Room Level: Upper Mezzanine) - May 17, 2023 - Abstract #APA2023APA_1521;
Overall, except for clozapine, these agents differ in only small degrees in their general efficacy in treating the positive symptoms associated with schizophrenia...Only in the past few years, we have seen the FDA approval of a glutamatergic drug, esketamine, and of a GABAergic drug, brexanolone...The first-line treatments for anxiety disorders has become selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, while insomnia treatment became dominated by more selective GABA-A modulators than benzodiazepines and a variety of off-label treatments. Recently, insomnia agents have emerged that more specifically target sleep, circuitry, and, as a result, provide improved risk-to-benefit ratio.Learning Objectives Objective One: At the conclusion of this session the participants will become familiar with the recently approved medications for the treatment of schizophrenia, depression, anxiety, and sleep disorders Objective Two: participants will be able to describe some of the new mechanisms of action of medications to treat schizophrenia, depression, anxiety, and sleep disorders current Objective Three: At the conclusion of this session the participants will be able to review some of the unanswered questions relevant to new medications to treat psychiatric disorders Objective Four: Objective Five:
- |||||||||| A Comprehensive Review of Novel FDA Approved Psychiatric Indications From 2018-2022 (Hall B Foyer, Exhibition Level Moscone South) - May 17, 2023 - Abstract #APA2023APA_968;
Clinical trials for each medication suggested favorable results in Phase III trials that lead to approval, along with current success in Phase IV trials as well. In 2018, Lucemyra (lofexidine) was approved for the treatment of opioid withdrawal.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Characterizing the Brexanolone-Induced Remission in Women with Postpartum Depression (Sapphire AB) - Apr 29, 2023 - Abstract #SOBP2023SOBP_126;
Optimal satisfaction with quality and stability of mood state occurred post remission , suggesting that patient reported satisfaction measures identify components of affective state not fully sampled by HAMD. The dramatic decreases in trait anxiety scores (32 +/-9.38) suggest this
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Trial completion date, Trial primary completion date: Effects Zulresso on Postpartum Psychosis (clinicaltrials.gov) - Apr 13, 2023
P1, N=10, Recruiting,
The dramatic decreases in trait anxiety scores (32 +/-9.38) suggest this Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
- |||||||||| Review, Journal: Novel antidepressant drugs: Beyond monoamine targets. (Pubmed Central) - Feb 27, 2023
The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: A Comprehensive Review on Postpartum Depression. (Pubmed Central) - Jan 24, 2023
Venlafaxine and desvenlafaxine are serotonin-norepinephrine reuptake inhibitors used for the relief of symptoms...Nowadays, women prefer psychological therapies, complementary health practices, and neuromodulatory interventions like electroconvulsive therapy more than previous pharmacological treatments of depression. Allopregnanolone drug made into sterile solution brexanolone leads to a rapid decline of PPD symptoms...We can easily prevent it by early diagnosis and timely care and management of the mother. Understanding the underlying pathophysiology would also go a long way in preventing and managing the disorder.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, zuranolone (SAGE-217) / Sage Therapeutics, Shionogi, Biogen
Review, Journal: Neurosteroids and translocator protein 18 kDa (TSPO) in depression: implications for synaptic plasticity, cognition, and treatment options. (Pubmed Central) - Dec 28, 2022
Regarding 3α-reduced neurosteroids, brexanolone, an intravenous formulation of allopregnanolone, has been approved for the treatment of postpartum depression and zuranolone, an orally available 3α-reduced neurosteroid, is currently being studied in major depressive disorder and postpartum depression. As such, 3α-reduced neurosteroids and TSPO ligands may constitute promising treatment approaches for affective disorders.
- |||||||||| Review, Journal: Noradrenergic Modulation of Stress Resilience. (Pubmed Central) - Dec 9, 2022
It has attracted increasing attention over the past decades with the revolution of modern neuroscience technologies. In this review article, we first briefly go over resilience-related concepts and introduce rodent paradigms for segregation of susceptibility and resilience, then highlight recent literature that identifies the neuronal and molecular substrates of active resilience in the locus coeruleus, and discuss possible future directions for resilience investigations.
- |||||||||| progesterone / Generic mfg.
Review, Journal: Many or too many progesterone membrane receptors? Clinical implications. (Pubmed Central) - Nov 18, 2022
CT1812 (Elayta™) is also being tested for the treatment of Alzheimer's disease (AD) in Phase 2 clinical trials, targeting the P4 receptor membrane component 1 (PGRMC1)/S2R complex. In this Review, we highlight emerging knowledge on the mechanisms of nongenomically initiated actions of P4 and its derivatives.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Enrollment open: Study on Allopregnanolone and Depression in Perimenopausal Women (clinicaltrials.gov) - Nov 10, 2022
P4, N=80, Recruiting,
In this Review, we highlight emerging knowledge on the mechanisms of nongenomically initiated actions of P4 and its derivatives. Not yet recruiting --> Recruiting
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, zuranolone (SAGE-217) / Sage Therapeutics, Shionogi, Biogen
Journal: Neuroinflammation and psychiatric disorders: relevance of C1q, translocator protein (18 kDa) (TSPO), and neurosteroids. (Pubmed Central) - Nov 2, 2022
Recently, neurosteroid compounds such as brexanolone or zuranolone have been reported to reduce depressive and anxiety symptoms in postpartum depression and major depressive disorder. In conclusion, compounds enhancing GABAergic neurotransmission such as neurosteroids and TSPO ligands, which also may exert anti-inflammatory properties in concert with immunomodulators such as C1q may open new avenues for the treatment of psychiatric disorders.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Brexanolone Therapeutics in Post-Partum Depression Involves Inhibition of Systemic Inflammatory Pathways (Grand Saguaro) - Oct 31, 2022 - Abstract #ACNP2022ACNP_816;
The data suggest that Brexanolone therapeutic actions involve the inhibition of inflammatory mediator production through desensitization of immune cells and changes in endogenous neurosteroid levels in blood. These data support the idea that inflammation plays a key role in post-partum depression and inhibition of specific inflammatory pathways underlies its therapeutic efficacy.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Differential Cellular Response to Allopregnanolone in Postpartum Depression (Grand Saguaro) - Oct 31, 2022 - Abstract #ACNP2022ACNP_19;
Together, these data highlight both ALLO-independent and -dependent molecular responses in PPD. While the Control:ALLO vs. PPD:ALLO comparisons of the transcriptional response reflect literature supporting ALLO’s modulation of synaptic signaling and GABA-related activity, the ultimately weak response of PPD LCLs to ALLO-treatment, especially compared to control LCLs, warrants further investigation.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Review, Journal: Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina. (Pubmed Central) - Oct 19, 2022
Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon...Both enantiomers are also equally effective in preserving retinal structure and function in an in vivo glaucoma model. These studies in the retina have important implications for the ongoing development of allopregnanolone and other neurosteroids as therapeutics for neuropsychiatric illnesses.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics, Ztalmy (ganaxolone oral) / Marinus, zuranolone (SAGE-217) / Sage Therapeutics, Shionogi, Biogen
Journal: Neuroactive steroids - new possibilities in the treatment of postpartum depression. (Pubmed Central) - Oct 16, 2022
In the case of severe depression, the patient is switched to pharmacological treatment, with sertraline being the most commonly used for this diagnosis...In addition to the registered brexanolone, another steroidal drug, zuranolone, is available in the third phase of the clinical trial...Another synthetic analogue of neuroactive allopregnanolone, known as ganaxolone, did not show a significant reduction in depressive symptoms in the second phase of the clinical trial compared to placebo. Nevertheless, it has great therapeutic potential in the treatment of various types of epilepsy.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Ketamine vs allopregnanolone – antidepressant effectiveness on a novel postpartum depression mice model (Poster area [IN-PERSON]) - Oct 13, 2022 - Abstract #ECNP2022ECNP_924;
Although brexanolone, an allopregnanolone-based treatment, has recently emerged as fundamental PPD treatment, there is scarce evidence on its neurobiological action mechanism...Finally, a reduction of vesicular transporters for GABA (VGAT) (F2,29=9.35; p<0.01) and glutamate (VGLUT1) (F2,29=3.55; p=0.07) in infralimbic cortex of MSEW dams was found and allopregnanolone increased these synaptic markers (F2,29=14.68; p<0.001; F2,29=11.78; p < 0.001 respectively). Finally, both (treatment; F2,26 =16.86; p < 0.001) ketamine (p<0.05) and allopregnanolone (p<0.001) increased adult hippocampal neurogenesis, restoring the lower levels of cellular proliferation presented in MSEW females (F1,26=6.29; p<0.05).We propose a new mice model that recapitulates the core symptomatology and alterations in glutamatergic and GABAergic systems shown in PPD patients, which allows us to investigate the therapeutic mechanisms of allopregnanolone and ketamine.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Impaired autophagy in high passaged human embryonic kidney 293 (HEK) cells (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_9471;
Given recent evidence that some novel psychiatric treatments, such as the neuroactive steroid (NAS) allopregnanolone (AlloP, Brexanolone), may target autophagy, we designed a stably transfected HEK cell model to assay NAS effects on autophagy...We conclude that passage number in immortalized HEK cells affects autophagy and opens possibilities of studying the transcriptional/epigenetic factors regulating autophagic flux, including lysosomal pH or protease dysfunction. Our results could be consistent with previous literature showing that autophagy is decreased with age; however, cellular senescence, implicated in prior work, is likely not involved given the immortalized nature of the HEK cell line.
- |||||||||| Differential network activity of benzodiazepines and neuroactive steroids observed with cortical EEG in rat. (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_4742;
Increased θ-band power was observed clinically with zuranolone (Antonoudiou 2022), whereas reduced θ-band power was reported in humans with lorazepam (Gilles 2002)...All compounds increased β-band power. The differential effects on θ-band power in rat EEG recordings between NAS GABAAR PAMs and the other GABAergic compounds tested may reflect the differential modulation of GABAAR subpopulations, since only the NAS GABAAR PAMs in this study modulate both γ and δ subunit-containing GABAARs.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Differential Transcriptomic Signatures Before and After Allopregnanolone in Postpartum Depression Cell Lines (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_3320;
Grant Support: Bench to Bedside Program Award #480670, NIH R21MH101409Given the health consequences, societal burden, and prevalence of postpartum depression (PPD), the recent FDA-approval of Brexanolone is an encouraging advance for its treatment...These preliminary data highlight both ALLO -independent and -dependent molecular responses in PPD. Taken together, the striking lack of overlap in DEGs between diagnostic groups after ALLO treatment may suggest that ALLO’s therapeutic and/or mechanistic response could be diagnosis-dependent.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Deficits in endogenous neurosteroidogenesis contributes to network and behavioral consequences of chronic stress (SDCC Halls B-H) - Oct 10, 2022 - Abstract #Neuroscience2022NEUROSCIENCE_1581;
Zulresso, a proprietary formulation of the endogenous 5α-reduced neurosteroid allopregnanolone, was recently approved for the treatment of postpartum depression...These findings suggest that deficits in endogenous neurosteroid signaling contribute to the behavioral deficits associated with chronic stress. Further, these studies suggest that the therapeutic efficacy of 5α-reduced neurosteroid-based treatments may be due to their ability to directly target the underlying pathophysiology of depressive disorders.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Implementation of a Hospital-based Brexanolone Program. (Pubmed Central) - Sep 16, 2022
Delivering brexanolone treatment to patients in need requires overcoming some logistical and clinical challenges that are unique to this approach. This brief report describes the process by which a university-affiliated obstetric-gynecologic hospital in the northeast United States successfully implemented a program to administer this novel treatment to women with PPD.
- |||||||||| Zulresso (brexanolone) / Sage Therapeutics
Journal: Formulary Drug Reviews: Brexanolone Injection. (Pubmed Central) - Sep 13, 2022
Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433.
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