Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression

Powell, Jason; Garland, Scott; Preston, Kayla; Piszczatoski, Chris

doi:10.1177/1060028019873320

Cited by 68 publications

(31 citation statements)

References 12 publications

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“…Downstream enzymes including 5α-reductase and 3α-hydroxysteroid dehydrogenase then catalyze the conversion of the hormones into other types of neuroactive steroids. Allopregnanolone, a 5α-reduced progesterone metabolite synthesized by the brain, was recently approved by the U.S. Food and Drug Administration (FDA) as Zulresso™ for treatment of postpartum depression (196). It is a strong positive allosteric GABA A receptor modulator and is deficient in patients with depression (243) (52).…”

Section: Sex Steroidsmentioning

confidence: 99%

Gut feelings: the microbiota-gut-brain axis on steroids

Savidge

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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The intricate connection between central and enteric nervous systems is well established with emerging evidence linking gut microbiota function as a significant new contributor to gut-brain axis signaling. Several microbial signals contribute to altered gut-brain communications, with steroids representing an important biological class that impacts central and enteric nervous system function. Neuroactive steroids contribute pathologically to neurological disorders, including dementia and depression, by modulating the activity of neuroreceptors. However, limited information is available on the influence of neuroactive steroids on the enteric nervous system and gastrointestinal function. In this review, we outline how steroids can modulate enteric nervous system function by focusing on their influence on different receptors that are present in the intestine in health and disease. We also highlight the potential role of the gut microbiota in modulating neuroactive steroid signaling along the gut-brain axis.

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Section: Sex Steroidsmentioning

confidence: 99%

Gut feelings: the microbiota-gut-brain axis on steroids

Savidge

2022

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…It has been reported that ALLO is an allosteric regulator of GABA receptors playing a role in depression and anxiety [33], as well as a variety of neurodegenerative diseases such as diabetic neuropathy [34], Alzheimer's disease [35] and Parkinson's disease [36]. It has been investigated for the treatment of Severe Postpartum Depression as the main ingredient of Zulresso (the rst FDA-authorized PPD inhibitor) [37]. Eminently, our nding is the rst time revealing the novel pharmacological activity of ALLO against in uenza virus with broad-spectrum and identi ed ALLO playing an antiviral role in the replication period in vitro.…”

Section: Discussionmentioning

confidence: 99%

Discovery of Allopregnanolone Against Influenza Virus With Broad Spectrum in Vitro

Wang

Cao

2021

Preprint

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Background: Influenza virus infection with seasonal or occasional but devastating morbidity and mortality, is a severe threat to public health. The frequent emergence of resistant viral strains limited application of current antivirals and posing an urgent need for novel antiviral therapies. Natural products offered a broad prospect in the screening and development of new influenza inhibitors.Methods: In this research, a high-throughput antiviral screening for 891 natural products was performed based on a recombinant reporter influenza A virus. According to the cytotoxicity assay and dose-response relationship, alloprogesterone (ALLO), as the positive hit was selected, and verified by viral titer reduction assay and immunofluorescence using a wild-type virus. Followingly, we explored its antiviral potency of counteracting with IAV and IBV, and preliminary investigated the mechanism of ALLO through time-of-addition assay and mini-replicon system.Results: Under the criteria of 80% inhibition and 70% cell viability, ALLO was screened out and confirmed antiviral activity in varied cells. The inhibitory effect of ALLO against influenza virus with a dose-dependent manner and significantly reduced viral yield of five different influenza viruses in the presence of 40 µM ALLO, including oseltamivir-resistant virus. Moreover, ALLO exhibited no influence on IAV entry or release during the viral replication cycle, but obviously interfered with the genome replication regarding post-infection 2 hrs to 6 hrs, which is consistent with the evidence of decreased polymerase activity.Conclusions: In summary, we firstly identified a new pharmacological activity of ALLO, as a broad spectrum inhibitor for treatment influenza infections, targeting viral replication stage and possessing great value of further development.

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“…Additionally, using risk factors for MDD with peripartum onset, such as low levels of social support and a history of depression, could help with starting interventions early on with high-risk patients [12]. Finally, neurosteroids, such as brexanolone, are a promising approach to treating MDD with peripartum onset; further research into this class of compounds may lead to the discovery of more efficacious treatments for MDD with peripartum onset [13].…”

Section: Discussionmentioning

confidence: 99%

A Case of Major Depressive Disorder With Peripartum Onset With Heralding Symptoms

Narlesky¹,

Lemp

Braaten³

et al. 2020

Cureus

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This report describes a case of major depressive disorder with peripartum onset in a 24-yearold African-American female who was admitted to the inpatient psychiatric facility after a suicide attempt. The patient demonstrated what we will describe as heralding symptoms during the birth of her second child, but her symptoms dramatically worsened one month prior to her admission with the birth of her third child. The patient presented with anxiety and depressive symptoms, including decreased energy, disrupted sleep patterns, and emotional lability. At the time of her admission, the patient had failed treatment with bupropion, which had been prescribed by her obstetrician. During her stay, the patient was treated with fluoxetine and participated in group therapy sessions. The patient gradually exhibited improvement in her depressive symptoms during the course of her six-day stay. At the time of discharge, the patient's depression was adequately managed with her medication regimen, and she was eager to be reunited with her newborn child. This case highlights the idiosyncratic nature of major depressive disorder with peripartum onset and the need for providers to tailor the treatment to the patient's need.

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Brexanolone (Zulresso): Finally, an FDA-Approved Treatment for Postpartum Depression

Cited by 68 publications

References 12 publications

Gut feelings: the microbiota-gut-brain axis on steroids

Gut feelings: the microbiota-gut-brain axis on steroids

Discovery of Allopregnanolone Against Influenza Virus With Broad Spectrum in Vitro

A Case of Major Depressive Disorder With Peripartum Onset With Heralding Symptoms

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