Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression-Focus on Zuranolone

Postpartum depression (PPD) remains a significant health concern worldwide. Both non-pharmacological and pharmacological treatments are available for patients with PPD; however, the standard approach involving selective serotonin reuptake inhibitors (SSRIs) and other antidepressants fails to provide a rapid response. This narrative review presents basic clinical and epidemiological data on PPD, summarizes currently used pharmacotherapies of PPD, highlights their limitations, and discusses new therapies based on a revised understanding of the disease's pathogenesis. Numerous studies indicate that dysregulation of GABAergic neurotransmission, which may result from fluctuating levels of neuroactive steroids during pregnancy and the postpartum period, plays an important role in the complex pathology of PPD. Considering this, neuroactive steroids, which act as positive allosteric modulators of central GABA_A receptors (GABA_ARs), may offer new promising avenues for treating PPD. The first rapid-acting neurosteroid approved by the FDA to treat PPD in women is brexanolone, although its use is constrained by pharmacokinetic properties. The first oral neuroactive steroid-based antidepressant approved by the FDA for PPD is zuranolone. This review discusses the molecular mechanism of zuranolone action and the results of preclinical and clinical studies regarding the effectiveness and safety of the drug in treating PPD.