Postpartum depression (
PPD) is a unique subtype of
major depressive disorder and a substantial contributor to maternal morbidity and mortality. In addition to affecting the mother,
PPD can have short- and long-term consequences for the infant and partner. The precise etiology of
PPD is unknown, but proposed mechanisms include altered regulation of stress response pathways, such as the hypothalamic-pituitary-adrenal axis, and dysfunctional
gamma-aminobutyric acid (
GABA) signaling, and functional linkages exist between these pathways. Current
PPD pharmacotherapies are not directly related to these proposed pathophysiologies. In this review, we focus on the potential role of GABAergic signaling and the GABAA receptor positive allosteric modulator
allopregnanolone in
PPD. Data implicating GABAergic signaling and
allopregnanolone in
PPD are discussed in the context of the development of
brexanolone injection, an intravenous formulation of
allopregnanolone recently approved by the United States Food and Drug Administration for the treatment of adult women with
PPD.