Neuropharmacology of Ketamine and Its Use in the Treatment of Major Depressive Disorder: A Review.
Cureus April 1, 2025 Zach Papadopoulos 1 citation
Ketamine acts as a rapid antidepressant primarily by blocking N-methyl-D-aspartate receptors, though its effects also involve monoaminergic signaling, BDNF signaling, opioid receptor agonism, and neuroinflammation. Compared to SSRIs and tricyclic antidepressants, ketamine shows greater efficacy, faster onset, and better tolerability but has a shorter duration of action and accessibility issues. In a head-to-head trial, ketamine matched electroconvulsive therapy in efficacy for non-psychotic depression while providing faster relief. Further research is needed to optimize dosing, improve accessibility, and address risks like bladder toxicity and addiction.