Ketamine as a Rapid-Acting Antidepressant: A Scoping Review of Mechanisms and Efficacy in Treatment-Resistant Depression.
Psychopathology March 27, 2026 Xiaoran Ding, Yaping Wu, Juan Yang et al. 1 citation
Ketamine is a rapid-acting antidepressant, especially for treatment-resistant depression, working through multiple targets in the glutamatergic system. It blocks NMDA receptors, which disinhibits dopamine reward pathways and increases BDNF expression via eEF2K suppression, activating the mTOR pathway and enhancing synaptic plasticity. Neuroimaging shows ketamine rapidly reshapes prefrontal-limbic connectivity and normalizes brain activity. It has a fast onset and broad therapeutic window, but enantiomers and metabolites differ in effects. Long-term safety, dependence risk, and cognitive effects require monitoring. Future work should explore synergistic treatments and safer ketamine derivatives for precision psychiatry.