Investigational synthetic neuroactive steroid zuranolone in treatment of major depressive disorder with peripartum onset

Abstract

Major depressive disorder with peripartum onset or peripartum depression is a common condition experienced by a large proportion of women and to some extent even in men. The current treatment strategies involve the use of conventional pharmacotherapeutic classes of drugs like selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and psychotherapy methods in the management of this condition. In this article, we try to review and evaluate the pathophysiology of the condition along with the safety and efficacy of the novel investigational therapeutic drug zuranolone, which is a synthetic neuroactive steroid (NAS) that has shown promise in clinical trials for the management of conditions like major depressive disorder, peripartum depression and bipolar disorder. The synthetic NAS zuranolone is an orally bioavailable positive allosteric modulator of the gamma amino butyric acid (GABAA) receptor, which can regulate the action of the GABAergic pathway implicated in many depressive episodes and also affect the normal functioning of the hypothalmo pituitary-adrenal (HPA) axis which is the core pathophysiological cause behind major depressive disorder with peripartum onset.