Abstract
Esketamine, one of the enantiomers of ketamine, is a non-selective, non-competitive antagonist of the ionotropic N-methyl-D-aspartate receptors on inhibitory interneurons. Concomitant activation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors of pyramidal neurons triggers a cascade of neurotrophic events, growth factor release, dendritic budding, and synaptogenesis in the corticolimbic region.
The drug is administered intranasally and its adjuvant administration with oral serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors results in a rapid antidepressant effect. Esketamine is metabolised via cytochrome P450 isoenzymes 2B6 and 3A4, and no clinically relevant drug-drug interaction has yet been demonstrated.
Clinical trials of adjuvant antidepressant treatment with esketamine have demonstrated that the drug is effective and safe in the treatment of resistant depressive episodes. The most frequently reported adverse effects include dizziness, vertigo, dissociative states, nausea, headache, somnolence and dysgeusia.