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Mood Disorders
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Madeleine A. Becker, Tal E. Weinberger, Leigh J. Ocker
Brexanolone, a soluble IV formulation of the neuroactive steroid allopregnanolone, is the first medication approved by the FDA specifically for the treatment of postpartum depression. Allopregnanolone, a progesterone metabolite, is a potent allosteric modulator of GABAa receptors and has been shown to have significant effects on anxiety and depression in animal models. Allopregnanolone levels change in parallel with progesterone, reaching highest concentrations in the third trimester and decreasing abruptly after childbirth [128, 129]. Brexanolone dosing was designed to be comparable to allopregnanolone levels in the third trimester. Brexanolone is administered as a continuous 60-hour infusion, with a gradual decrease in dose until the infusion is stopped, allowing for a slow rather than abrupt decrease in allopregnanolone levels in a population which may be vulnerable to rapid hormonal fluctuation.
Perinatal Mood and Anxiety Disorder
Published in Nora Swan-Foster, Art Therapy and Childbearing Issues, 2020
In addition, as one of 23 facilities across the United States with a postpartum Maternal Mental Health program (ranging from Inpatient Perinatal Psychiatric Programs to Outpatient Perinatal Mental Health programs), our hospital has the only program that offers the latest FDA approved infusion to combat the symptoms of Postpartum Depression. The hormone infusion of brexanolone—a neuroactive steroid gamma-aminobutyric acid (GABA) and a receptor positive modulator—that is administered for 60 continuous hours. Eight of our postpartum mothers (after the center underwent a rigorous sequence of discussions with their insurance providers) were cleared to participate in an inpatient medical infusion process. These eight mothers were utilizing the PMADs program, but had seen little to no improvement in their mental well-being since the beginning of the outpatient program, even after approximately two to six months of individual and group facilitations. As such, they were introduced to the latest intervention through family discussions and an infusion information series. All eight women have seen a dramatic difference in their mental health as soon as 12 hours from the start of the infusion. The change has been extraordinary. From the onset, these mothers presented flat and apathetic and now have transformed to bright and passionate about life, love, and their new identities as mothers.
Preventing recurrence of postpartum depression by regulating sleep
Published in Expert Review of Neurotherapeutics, 2023
Verinder Sharma, Katherine M. Sharkey, Laura Palagini, Dwight Mazmanian, Michael Thomson
Further high-quality research is needed due to the paucity of drug and psychotherapeutic studies in the prevention of unipolar or bipolar postpartum depression. Following Wisner and colleagues’ pilot study of sertraline nearly 20 years ago, there have not been any controlled trials of antidepressants in the prevention of postpartum depression [34]. Brexanolone, the only FDA-approved drug for the treatment of postpartum depression has not been studied in the prevention of depression in women with major depressive disorder or bipolar disorder [90]. Extant literature on the topic, albeit limited, has focused exclusively on women with a history of postpartum depression [91]. Research is needed on the prevention of recurrence and the first occurrence of a major depressive episode in the postpartum period. However, conducting drug studies on women at risk of postpartum depression is challenging due to difficulties with recruitment and retention [92].
Neuroinflammation and psychiatric disorders: Relevance of C1q, translocator protein (18 kDa) (TSPO), and neurosteroids
Published in The World Journal of Biological Psychiatry, 2022
Rainer Rupprecht, Christian Rupprecht, Barbara Di Benedetto, Gerhard Rammes
Endogenous and synthetic 3α-reduced neurosteroids such as allopregnanolone are powerful positive allosteric modulators of GABAA receptors (Rupprecht 2003; Rupprecht et al. 2010). Meanwhile, it is quite clear that these compounds target both synaptic and extrasynaptic GABAA receptors (Locci and Pinna 2017; Althaus et al. 2020; Paul et al. 2020), which may contribute to their unique pharmacological profile. It has been shown that there is a disequilibrium of neurosteroids in anxiety disorders (Ströhle et al. 2003) and depression (Romeo et al. 1998), which can be corrected by SSRI treatment. Given that TSPO ligands may promote the synthesis of endogenous neurosteroids, targeting TSPO may be a valuable therapeutic approach for interfering with neurosteroidogenesis (Rupprecht et al. 2009, 2010). Another promising approach is the direct application of neurosteroids such as the intravenous formulation brexanolone (Meltzer-Brody et al. 2018) or the oral administration of zuranolone (SAGE-217) (Gunduz-Bruce et al. 2019). Intriguingly, these compounds may exert quite rapid antidepressant effects. While brexanolone has already been approved for the treatment of postpartum depression, the antidepressant properties of zuranolone have yet to be confirmed in further studies.
Evaluating brexanolone for the treatment of postpartum depression
Published in Expert Opinion on Pharmacotherapy, 2021
Brexanolone is chemically identical to endogenous allopregnanolone and, like allopregnanolone, acts as a positive allosteric modulator of the gamma-aminobutyric acid A receptor (GABAA) in the brain. GABA acts as an inhibitory neurotransmitter, and GABAA receptors are five-unit transmembrane ion channels that are found in intrasynaptic and extra synaptic sites as well as on glial cells. A number of preclinical and clinical studies have implicated reduced neuroactive steroid levels, in particular allopregnanolone, in mood and anxiety disorders (reviewed in [21,22]). For example, in animal models, neuronal levels of allopregnanolone rise during an acute stress, but with chronic stress decrease and correlate with depressive and anxiety-like behaviors [22]. Allopregnanolone levels rise across the course of pregnancy and precipitously drop after delivery, and some [23,24] but not all studies [25] have found that lower levels of allopregnanolone in pregnancy are associated with the development of PPD. Brexanolone is thus thought to target the decreased levels of allopregnanolone following childbirth, which may trigger a depressive episode in susceptible women, thus alleviating their depressive symptoms.