A single low dose of esketamine given at the start of cardiac valve surgery reduced rates of depression and anxiety one week after surgery. Among 142 patients, those receiving esketamine had a depression rate of 7.0% compared to 31.0% in the placebo group, and an anxiety rate of 11.3% versus 35.2%. Esketamine also lowered delirium incidence, improved pain, sleep, and recovery quality, and reduced inflammatory markers (IL-6, CRP) and a neuronal injury marker (S100β) while increasing brain-derived neurotrophic factor (BDNF). Side effects did not differ between groups.
Esketamine produces antidepressant effects in mice subjected to chronic restraint stress by activating glutamatergic neurons in the medial prefrontal cortex. In a study of 150 male C57BL/6J mice, those treated with esketamine showed reduced immobility in tail suspension and forced swim tests and increased sucrose preference compared with saline-treated controls. Immunofluorescence staining indicated higher c-Fos expression in glutamatergic neurons after esketamine treatment. Chemogenetic activation of these neurons mimicked the antidepressant effects, while their inhibition blocked esketamine's benefits.