Ketamine given intravenously rapidly reduces depressive symptoms, with effects lasting at least a week. In an analysis of 17 randomized controlled trials with 809 participants, the benefit over placebo was larger for patients who had already failed two or more prior antidepressant trials. However, no patient-level clinical or demographic characteristics—such as age, sex, or diagnosis—could predict who would respond best, limiting the ability to personalize ketamine prescriptions. The findings confirm ketamine's broad effectiveness for depression but show that precision medicine approaches cannot yet guide treatment decisions.
Current first-line antidepressants often take weeks to improve symptoms, but low-dose ketamine may work faster, even in treatment-resistant depression. This study compared the effects of ketamine infusion and electroconvulsive therapy (ECT) on biological markers related to stress and inflammation in patients with treatment-resistant depression versus healthy controls. Both treatments improved depressive symptoms. At baseline, patients showed differences in cortisol and kynurenine pathway metabolites compared to controls, though inflammatory markers were similar. After ECT, the cortisol awakening response decreased in responders. Ketamine showed a trend toward reduced kynurenine in responders but did not significantly alter any measured biomarkers.
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.