Ketamine improves symptoms in adolescents with treatment-resistant depression

Intravenous ketamine is well tolerated and demonstrates significant short-term efficacy in reducing depressive symptoms in adolescents with treatment-resistant depression as compared with an active placebo, according to a recent study.

Seventeen adolescents (aged 13–17 years) with a diagnosis of major depressive disorder participated in this proof-of-concept randomized, double-blind, single-dose crossover clinical trial. They received a single intravenous infusion of either ketamine 0.5 mg/kg over 40 min or midazolam 0.045 mg/kg over 40 min, and the alternate compound 2 weeks later.

All participants had previously received at least one antidepressant medication and met the severity criterion of a score >40 on the Children’s Depression Rating Scale–Revised. Score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment was the primary outcome measure.

A single ketamine infusion resulted in a significant decrease in depressive symptoms 24 hrs after administration compared with midazolam (midazolam: mean MADRS score, 24.13, 95 percent confidence interval [CI], 18.21–30.04; ketamine: mean MADRS score, 15.44, 95 percent CI, 10.51–20.37; mean difference, –8.69, 95 percent CI, –16.72 to –0.65; effect size, 0.78).

Secondary analyses showed that treatment gains associated with ketamine persisted up to 14 days after treatment. Several participants had a response to ketamine during the first 3 days following infusion as compared with midazolam (76 percent and 35 percent, respectively).

Furthermore, ketamine correlated with transient, self-limited dissociative symptoms that affected participant blinding, but no serious adverse events were reported.

“Adolescent depression is prevalent and is associated with significant morbidity and mortality,” the authors said.