ACLP Foundation Research Professor Award: From Bench to Bedside: The Development of Novel Neurosteroid Therapeutics as an Innovative, ‎Rapidly Acting Treatment for Postpartum Depression

There is a great need for innovation in perinatal mental health. While psychotherapy remains a first ‎line treatment for mild to moderate symptoms, pharmacologic therapy is an important treatment tool ‎for moderate to severe symptoms of perinatal depression and in particular, postpartum depression ‎‎(PPD), one of the most common and serious complications of childbirth. Given that a significant ‎number of patients do not respond to current treatment, novel pharmacologic therapies are needed ‎to increase our ability to effectively treat most women with PPD to remission. This talk will describe ‎novel neurosteroid therapeutics with a focus on their development, clinical trial data, current ‎practices, and future directions in perinatal mental health.‎

We discuss the clinical impact of brexanolone and several other neurosteroids, particularly as they ‎relate to the treatment of postpartum depression (PPD). There has been increasing interest in GABA ‎signaling and modulation as it pertains to the development of altered circuity and depressive states. ‎This scientific underpinning served as the rationale for the initial development of brexanolone. We ‎review the clinical trials supporting its Food and Drug Administration (FDA) approval as the first rapidly ‎acting antidepressant specific for PPD, and the subsequent development of a clinical brexanolone ‎program at an academic medical center, highlighting new research and data from that site as well as ‎the challenges with the delivery of this I.V. drug. We will also discuss the newly approved neurosteroid, ‎zuranolone, the first oral drug for postpartum depression, and discuss other neurosteroid agents ‎under development including ganaxolone.‎

Further, we will review new data of the genetic underpinning of PPD, and other data demonstrating ‎that brexanolone causes inhibition of inflammatory signaling post-infusion, suggesting that ‎inflammatory signaling may contribute to the etiology of PPD. Ultimately, the hope is that these novel ‎neurosteroid therapeutics will provide fast-acting treatment for these impairing disorders and improve ‎of our understanding of the underlying mechanisms of PPD and other depressive disorders.‎