EClinicalMedicine
August 1, 2023
Stevan Nikolin, Anthony Rodgers, Andreas Schwaab et al.
166 citations
A systematic review and meta-analysis of 49 randomized controlled trials with 3,299 participants found that racemic ketamine produced larger reductions in depression severity than esketamine, both immediately after the first dose and during repeated dosing. Higher doses were more effective than lower doses. After the final dose, only racemic ketamine maintained a significant effect; esketamine did not. Dropout rates were similar between treatment and control conditions.
Research square
February 12, 2026
Jenessa Johnston, Greg Jones, Shiyong Peng et al.
Rapid-acting antidepressants such as ketamine and psychedelics share common downstream effects on gene expression in human cortical neurons, despite targeting different initial receptors. Using stem cells from people with treatment-resistant depression and healthy volunteers, neurons were treated with several compounds. After 6 and 24 hours, gene activity was highly correlated across all drugs, converging on pathways related to inflammation, mTORC1 signaling, and cell growth. One compound, HNK, increased gene activity in excitatory neurons and decreased it in inhibitory neurons. These gene changes matched protein changes in spinal fluid from people given ketamine, supporting the model's relevance for studying antidepressant mechanisms.
Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition
September 16, 2025
Jen Evans, Carlos Zarate
Ketamine, a rapid-acting antidepressant, changes functional connectivity in the brain in ways that correlate with the density of receptors known to be involved in depression. In a double-blind placebo-controlled trial, participants received an infusion of ketamine or placebo while undergoing resting-state fMRI. The resulting connectivity changes matched several receptor types linked to depression. This method may help evaluate how new drugs affect the brain.