Innovative Approaches to Depression Therapy: The Antidepressant Efficacy and Mechanisms of General Anesthetics.
Current neuropharmacology April 16, 2026 Xiangying Wei, Shan Xu, Zhaoqiong Zhu
General anesthetics such as ketamine, propofol, isoflurane, and certain opioids show rapid and sustained antidepressant effects in both preclinical and clinical settings, offering a new therapeutic avenue for treatment-resistant depression, which affects about one-third of patients. These effects go beyond traditional monoamine regulation, involving modulation of glutamate and GABA signals and restoration of synaptic plasticity in damaged brain circuits. Despite the promise, balancing benefits against risks and establishing consistent treatment guidelines remain critical for developing new rapid-acting antidepressants for patients who do not respond to standard care.