Several anesthetic agents beyond ketamine show antidepressant effects, including nitrous oxide, propofol, isoflurane, sevoflurane, dexmedetomidine, and xenon. This review examines clinical and basic science studies on these anesthetics for treating depression. The authors propose that anesthetics may alleviate depression by modulating brain dynamics that alter arousal states, linking anesthetic mechanisms to depression pathophysiology and findings from other treatments. The work suggests that repurposing anesthetics could offer new options for major depressive disorder and treatment-resistant depression.
Psychedelics reopen critical periods, induce metaplasticity, and reorganize the extracellular matrix, which helps explain their diverse, durable, and context-dependent therapeutic effects. This neurobiological evidence challenges the biochemical imbalance model that has dominated translational neuroscience since the 1950s and supports a learning model that better accounts for psychedelics' unique therapeutic profile.