Background: Postpartum depression (PPD) is a serious affective disorder that poses a substantial threat to the wellbeing of both mother and child. Due to emotional stigmatization and lack of targeted treatments, PPD remains underdiagnosed and undertreated. Additionally, untreated cases of severe PPD produce significant economic strain to public health. Studies in mice have demonstrated that fluctuations in reproductive hormone, allopregnanolone, induce downregulation of GABAA receptors in the brain, which are responsible for mood dysregulation and depressive symptoms in the postpartum period. Three recent clinical studies have shown great potential for using brexanolone, a neuroactive allopregnanolone derivative, in addressing the underlying pathophysiology of PPD.
Methods: A comprehensive search of available medical literature was conducted using PubMed, Google Scholar, EBSCO-Host, Web of Science, PsycINFO, and CINAHL. The key search terms included brexanolone, neuroactive steroid, GABAA receptor modulator, postpartum, and depression. A risk of bias assessment was performed.
Results: The initial search across 4 databases yielded 135 results. After eliminating duplicates, 3 studies met inclusion criteria and were clinically relevant. Of these articles, 2 were high-quality randomized controlled trials that showed a rapid and significant reduction in mean HAM-D score in participants treated with a 60-hour brexanolone infusion.
Conclusion: This critically appraised topic demonstrates that neuroactive progesterone derivative allopregnanolone, has shown promise in treating women with severe postpartum depression. Recent clinical trials support the rationale that targeting GABAA receptors is efficacious in the development of pharmacotherapy for PPD patients. The FDA’s approval of brexanalone for the treatment of PPD provides the opportunity for further research in pharmacotherapy for mood disorders with a specific focus on depressive subtypes.
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