Brexanolone: First Global Approval

@article{Scott2019BrexanoloneFG,
  title={Brexanolone: First Global Approval},
  author={Lesley J. Scott},
  journal={Drugs},
  year={2019},
  volume={79},
  pages={779-783}
}
  • L. Scott
  • Published 1 May 2019
  • Medicine
  • Drugs
Brexanolone (ZULRESSO™) is an intravenously administered, small molecule, neuroactive steroid GABAA receptor positive allosteric modulator that was developed by Sage Therapeutics under license to the University of California for the treatment of postpartum depression (PPD). The formulation is a mixture of allopregnanolone, an endogenous inhibitory pregnane neurosteroid, and sulfobutylether-beta-cyclodextrin (a solubilizing agent). In mid-March 2019 brexanolone received its first global approval… Expand
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References

SHOWING 1-10 OF 18 REFERENCES
Open‐label, proof‐of‐concept study of brexanolone in the treatment of severe postpartum depression
TLDR
Brexanolone (USAN; formerly SAGE‐547 Injection), a proprietary injectable allopregnanolone formulation, was evaluated as a treatment for severe PPD in a proof‐of‐concept, open‐label study. Expand
Brexanolone: an allosteric modulator of GABA-A receptors in the rapid treatment of postpartum depression
TLDR
Findings lend support to the hypothesis that changes in neuroactive steroid concentrations during pregnancy and postpartum are capable of provoking affective dysregulation in mothers and reflect the relative involvement of various functional neuroanatomical systems. Expand
Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial
TLDR
In women with severe post-partum depression, infusion of brexanolone resulted in a significant and clinically meaningful reduction in HAM-D total score, compared with placebo, which supports the rationale for targeting synaptic and extrasynaptic GABAA receptors in the development of therapies for patients with post- partum depression. Expand
Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials
TLDR
Braxanolone injection (formerly SAGE-547 injection), a positive allosteric modulator of γ-aminobutyric-acid type A (GABAA) receptors, is assessed for the treatment of moderate to severe post-partum depression. Expand
Neurosteroids, stress and depression: Potential therapeutic opportunities
TLDR
The mechanisms of neurosteroid action in brain are reviewed with an emphasis on those neurosteroids that potently modulate the function of GABA(A) receptors, and potential strategies that can be used to manipulate CNS neurosteroidal synthesis and function for therapeutic purposes are discussed. Expand
Pharmacotherapy of Postpartum Depression: Current Approaches and Novel Drug Development
TLDR
A recent series of open-label and placebo-controlled randomized clinical trials of brexanolone in postpartum depression demonstrated a rapid reduction in depressive symptoms, and has led to the submission for regulatory approval to the US Food and Drug Administration. Expand
Allopregnanolone as a mediator of affective switching in reproductive mood disorders
TLDR
The role of the “neuroactive” steroids estradiol and progesterone in reproductive endocrine-related mood disorders are described and potential mechanisms by which ALLO might contribute to their pathophysiology are highlighted. Expand
Brexanolone iv efficacy in postpartum depression in three pivotal trials: montgomery‐åsberg depression rating scale assessment: 86
TLDR
This abstract presents the results of a secondary measure, the Montgomery-Åsberg Depression Rating Scale (MADRS), which met the primary efficacy endpoint with a significantly greater change from baseline in Hamilton Rating Scale for Depression (HAM-D) total score at Hour 60 than placebo (PBO). Expand
The role of reproductive hormones in postpartum depression
TLDR
The hypothesis that fluctuations in reproductive hormone levels during pregnancy and the postpartum period trigger PPD in susceptible women is examined to propose that these women constitute a “hormone-sensitive” PPD phenotype, which should be studied independent of other PPD phenotypes to identify underlying pathophysiology and develop novel treatment targets. Expand
When depression complicates childbearing: guidelines for screening and treatment during antenatal and postpartum obstetric care.
TLDR
The peripartum period is a prime time for symptom exacerbation and relapse of depressive episodes, and treatment may be complex and requires input from a multidisciplinary team, including an obstetrician, psychiatrist, and pediatrician. Expand
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