A single intravenous infusion of ketamine (0.5 mg/kg over 40 minutes) significantly reduced depressive symptoms in adolescents with major depressive disorder 24 hours later compared with the active placebo midazolam. The treatment effects appeared to persist for 14 days on one depression scale but not another. A greater proportion of participants responded to ketamine during the first three days after infusion (76%) compared with midazolam (35%). Ketamine caused transient dissociative symptoms but no serious adverse events.
Ketamine works as a rapid antidepressant for some but not all patients. In adolescents with treatment-resistant depression, those who had tried fewer antidepressant medications and augmentation treatments, had a shorter current depressive episode, and were currently taking a selective serotonin reuptake inhibitor (rather than a serotonin–norepinephrine reuptake inhibitor) were more likely to experience symptom improvement one and seven days after a single dose of ketamine. These findings are preliminary due to the small sample and multiple analyses, and more research is needed before using such predictors in clinical practice.