Ketamine, a rapid-acting antidepressant for treatment-resistant depression, appears to reduce inflammation in at least some depressed patients. A systematic review of 9 human studies and 22 rodent studies found strong evidence in rodents that ketamine lowers pro-inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, and also affects tryptophan metabolism by decreasing the enzyme indoleamine 2,3-dioxygenase. Human studies showed less consistent results but most reported decreases in peripheral inflammation including the same cytokines. Preliminary evidence also suggested reduced activation of the neurotoxic arm of the kynurenine pathway. Future research should investigate markers in the central nervous system and the clinical relevance of these inflammatory changes.
Ketamine, a dissociative anesthetic, produces rapid antidepressant effects at low doses, which may be partly due to its anti-inflammatory actions. This review examines ketamine's antidepressant properties and its influence on peripheral and central inflammation, aiming to clarify mechanisms that could make it a dual-action treatment for treatment-resistant depression (TRD) and suicidal ideation. Inflammation is linked to major depressive disorder (MDD) and poor treatment response, so medications that quickly address both inflammation and depressive symptoms could improve personalized care for psychiatric emergencies.