Loss of parvalbumin-immunoreactivity in mouse brain regions after repeated intermittent administration of esketamine, but not R-ketamine

Clinical use of the rapid antidepressant drug ketamine is limited, due to psychotomimetic side effects. R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to S-ketamine (esketamine), since it is free of psychotomimetic side effects. Repeated, intermittent administration of esketamine (10 mg/kg, once per week for 8-weeks), but not R-ketamine, caused loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex and hippocampus of mouse brains, regions associated with psychosis. This study suggests that repeated intermittent use of R-ketamine is safer than esketamine in the treatment of depression.