Allopregnanolone in postpartum depression: Role in pathophysiology and treatment

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 GABA(A) 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.