Brexanolone: A Novel Drug for the Treatment of Postpartum Depression

Abstract

Objectives: To review the pharmacology, efficacy, and safety of Brexanolone and define its role in the treatment of postpartum depression. Date Sources: A MEDLINE/PubMed search was conducted (1980-May 2020) using the following keywords: postpartum depression, antidepressants, pharmacologic therapy, drug therapy, and brexanolone to identify relevant articles. Study Selection/Data Extraction: Literature search was limited to human studies published in the English language. Phase I, II, and III studies evaluating the pharmacology, efficacy, safety of brexanolone for postpartum depression were included. Bibliographies of relevant articles evaluating postpartum depression and treatment were reviewed for additional citations and background information. Data Synthesis: Brexanolone is a soluble, proprietary, injectable formulation of allopregnanolone, a neuroactive steroid that modulates neuronal excitability. Allopregnanolone levels increase during pregnancy and decrease substantially after birth. These fluctuations have profound effects on anxiety and depression. Three clinical trials established the efficacy and safety of brexanolone in the treatment of postpartum depression. In all 3 trials, brexanolone had an acceptable safety profile and was well tolerated. The most common adverse effects were loss of consciousness, sedation, dry mouth, headache, dizziness, and flushing. Due to sudden loss of consciousness and excessive sedation, continuous pulse oximetry is recommended. Conclusion: Brexanolone has a novel mechanism of action and appears to be safe and effective for the treatment of moderate to severe postpartum depression. At present, high cost, serious adverse effects, and restricted access may limit its use in clinical practice.

The Impact of Sex Hormones on Transcranial Magnetic Stimulation Measures of Cortical Excitability: A Systematic Review and Considerations for Clinical Practice

“…Interestingly, the novel antidepressant brexanolone is an allopregnanolone analog used to treat postpartum depression. At this time, brexanolone is a continuous intravenous infusion over two and a half days and not used for ongoing treatment 45 . Other neuroactive steroids under investigation for roles in neuropsychiatric illness are pregnenolone, pregnenolone sulfate, Dehydroepiandrosterone (DHEA), and DHEA-sulfate; however, none have been evaluated in the context of neuromodulation with TMS.…”

“…and not used for ongoing treatment. 45 Other neuroactive steroids under investigation for roles in neuropsychiatric illness are pregnenolone, pregnenolone sulfate, Dehydroepiandrosterone (DHEA), and DHEA-sulfate; however, none have been evaluated in the context of neuromodulation with TMS. If combined with a TMS protocol, for example, one would be advised to monitor the motor threshold frequently.…”

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin

“…This could help identify specific groups of patients in which chrysin could be used as an alternative for the treatment of anxiety and depression disorders, where their etiology could be related to changes in steroid hormones, neurotransmitters, oxidative stress, or neuro-inflammatory processes. It could permit the evaluation of therapeutic effects of chrysin in human patients, as has occurred, for example, with the neurosteroid allopregnanlone [ 83 , 87 , 97 , 98 ], and the mechanism of action underlying its anxiolytic and antidepressant effects is shared with those produced by the flavonoid chrysin.…”

Neurosteroid Modulation of Synaptic and Extrasynaptic GABAA Receptors of the Mouse Nucleus Accumbens

“…In the 1980s, neurosteroids, typified by allopregnanolone, were identified as endogenous, potent, positive allosteric modulators (PAMs) of the GABA A R [1]. This discovery encouraged exploration of the therapeutic potential of endogenous and synthetic neuroactive steroids including use as anticonvulsants, analgesics, anxiolytics, and antidepressants [2][3][4][5][6][7][8][9][10]. Recently, this potential was realised with the FDA approval of allopregnanolone (brexanolone)…”

“…Biomolecules 2024, 14, 460 2 of 22 and a synthetic derivative SAGE-217 (zuranolone) to treat PPD [2][3][4][5][6][7][8][9]11], reinvigorating interest in targeting GABA A Rs in relevant neural pathways for the treatment of depressive disorders [2][3][4][5][6][7][8][9]11].…”