GABAA Receptor Modulators as Emerging Therapeutic Agents for Depressive Disorders.

Depression is a serious mental disorder that affects individuals across diverse demographic and socioeconomic groups. Its pathophysiology is multifactorial and incompletely understood, and currently available pharmacological treatments remain limited in efficacy and scope. This article examines the involvement of the gamma-aminobutyric acid (GABA)ergic system in the pathogenesis of depression and reviews the pharmacological effects, therapeutic efficacy, and recent research developments related to various GABAA receptor modulators in the treatment of depressive disorders, including benzodiazepines, intravenous anesthetics, and neurosteroids. These agents may exert antidepressant and anxiolytic effects through modulation and restoration of GABAergic neurotransmission. In addition, certain agents, such as etomidate and allopregnanolone, have been reported to enhance synaptic plasticity and attenuate neuroinflammatory processes, thereby contributing to the reduction of depressive symptoms through multiple neurobiological mechanisms.