Brain : a journal of neurology
June 30, 2025
Sara Costi, Chloe Wigg, Erdem Pulcu et al.
3 citations
Ketamine, long used as an anesthetic, was first identified in 2000 as a fast-acting antidepressant. A single dose alleviates depressive symptoms, including anhedonia, within hours, and effects last for days. Research in animals indicates ketamine rapidly influences brain regions involved in punishment and reward processing, reverses negative affective biases in memories, and promotes stress resilience. Translating these findings to humans is ongoing, with emerging evidence suggesting similar mechanisms in healthy volunteers and patients. Clinical use is limited by acute side effects and unknown long-term safety. Understanding ketamine's mechanisms may guide development of safer rapid-acting antidepressants.
EBioMedicine
December 1, 2025
Kiranpreet Gill, Angharad N De Cates, Chantelle Wiseman et al.
Nitrous oxide, a gas that blocks the N-methyl-d-aspartate receptor, shows rapid but short-lived antidepressant effects in early-phase trials. Pooled results from three trials using a single 50% dose found significant reductions in depressive symptoms at 2 hours and 24 hours after inhalation, but not at one week. Side effects were mild and temporary, with the 25% dose being better tolerated. Most trials were small, early-phase studies focused on short-term outcomes in adults with major depressive disorder or treatment-resistant depression. Whether nitrous oxide will become a useful clinical treatment depends on whether its effects can be sustained through optimized or repeated dosing.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
March 1, 2025
Ella Williams, Ursule Taujanskaite, Sunjeev K Kamboj et al.
Nitrous oxide (N2O), a gas used for sedation and pain relief, shows rapid-acting antidepressant effects in treatment-resistant depression. Subanaesthetic doses (50%) can disrupt the reconsolidation of maladaptive memories in healthy people and across disorders. Negative memory biases contribute to depression, and disrupting affective memory reconsolidation may be how N2O works. This narrative review introduces evidence for N2O's antidepressant profile, evaluates its clinical use versus other treatments, and proposes a memory-based mechanism of action.