Repeated intravenous ketamine infusions are no more effective than a placebo (midazolam) for reducing depressive symptoms in inpatients with moderate to severe depression. In a randomized clinical trial, there was no statistically significant difference between the ketamine and midazolam groups on the primary outcome of depression severity at the end of treatment. No significant differences were found on secondary measures of efficacy, cognition, economic outcomes, or quality of life. These results do not support a superior antidepressant effect for serial intravenous ketamine as an addition to usual inpatient care.
A pilot trial tested four once-weekly ketamine infusions added to usual inpatient care for depression. Ketamine, which blocks the NMDA receptor and targets glutamate, was compared with midazolam. Among 25 hospitalized participants, there were no major differences in depression scores between the ketamine and midazolam groups. The infusions were generally safe and well tolerated. The trial suggests that a larger definitive trial of adjunctive ketamine is feasible.