Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.
Frontiers in psychiatry January 1, 2025 Congyi Li, Zhihui Wang, Xinman Ye et al.
Several anesthetic agents—ketamine, propofol, nitrous oxide, sevoflurane, and isoflurane—show promise as rapid antidepressants, especially for treatment-resistant depression. Their effects appear to involve modulation of glutamate and GABA signaling, interactions with serotonin, dopamine, and norepinephrine, activation of BDNF and VGF pathways, regulation of the HPA axis, and suppression of inflammation. These mechanisms overlap with core depression-related changes. While traditional antidepressants have limited efficacy and delayed onset, anesthetics offer faster alternatives. However, their precise mechanisms, long-term safety, and optimal clinical use remain unclear. This review summarizes recent experimental and clinical research on these agents, highlighting molecular mechanisms, therapeutic potential, and current limitations.