Pharmacotherapeutic approaches to treating postpartum depression: a focus on GABA A receptor positive allosteric modulators

INTRODUCTION: R) through neuroactive steroids (NASs), highlighting the role of GABAergic and stress-axis dysregulation in PPD. AREAS COVERED: R modulation in the pathophysiology of PPD, including the GABAergic deficit hypothesis and the impact of peripartum hormonal fluctuations. We review clinical trial data supporting the efficacy, safety, and rapid onset of brexanolone and zuranolone, as well as their sustained antidepressant effects. In addition, we discuss emerging NAS-based therapeutics and preclinical models demonstrating the role of GABAergic plasticity and stress-axis regulation in PPD. Literature was identified through review of clinical, observational, and preclinical studies relevant to NAS signaling and GABAergic function. EXPERT OPINION: R represent a novel and promising approach to the treatment of PPD, with rapid and sustained antidepressant effects. These agents may ultimately have broader applications across psychiatric disorders characterized by GABAergic dysfunction, although further research is needed to clarify their role and optimize their use.