A single intravenous dose of ketamine (0.5 mg/kg) significantly reduced depressive symptoms in adolescents with major depressive disorder compared with an active placebo (midazolam) 24 hours after infusion, with a large effect size. The improvement appeared to persist for up to 14 days on one depression scale but not another. More participants responded to ketamine during the first three days (76%) than to midazolam (35%). Ketamine caused temporary dissociative symptoms but no serious adverse events. This first controlled trial in adolescents suggests ketamine is well tolerated and has short-term efficacy for treatment-resistant depression.
Ketamine is an effective rapid-acting antidepressant, but its acute dissociative effects do not predict depression response in adolescents with treatment-resistant depression. In a secondary analysis of 16 adolescents from a crossover trial, no significant associations were found between dissociative symptoms—measured by the Clinician-Administered Dissociative States Scale—and depression improvement or response one day after ketamine infusion. When receiving the control drug midazolam, higher depersonalization symptoms were linked to less improvement. These findings contrast with some adult studies and may be limited by the small sample size, which reduces the ability to detect small or medium effects.