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.
A single intravenous dose of ketamine (0.5 mg/kg over 40 minutes) rapidly reduces attentional bias toward sad stimuli in adults with moderate-to-severe depression. A novel dual-probe video task measuring attentional bias showed good test-retest reliability at one week and one month before treatment. In two studies totaling 83 participants, attentional bias decreased from before to 24 hours after ketamine infusion. In the first study, attentional bias correlated with clinician-rated depressive symptoms at each pretreatment assessment. In the second study, reductions in attentional bias correlated with symptom improvement. The findings suggest that reducing attentional bias may be a cognitive mechanism underlying ketamine's rapid antidepressant effects.