Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial
Jennifer B. Dwyer, Angeli Landeros‐Weisenberger, Jessica A. Johnson, Amalia Londoño Tobón, José M. Flores, Madeeha Nasir, Kevin G. Couloures, Gerard Sanacora, Michael H. Bloch
FOCUS The Journal of Lifelong Learning in Psychiatry April 1, 2022 DOI: 10.1176/appi.focus.22020004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, single-dose crossover clinical trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 17 |
| Population | Adolescents ages 13-17 with major depressive disorder who had previously tried at least one antidepressant medication and had a Children's Depression Rating Scale-Revised score >40 |
| Interventions | Ketamine Midazolam |
| Dose | 0.5 mg/kg over 40 minutes for ketamine; 0.045 mg/kg over 40 minutes for midazolam |
| Duration | Single infusion, with follow-up at 24 hours and up to 14 days after treatment |
| Topics | Depression Ketamine Esketamine |
| Keywords | Midazolam Depression economics Anesthesia Placebo Rating scale Randomized controlled trial Crossover study Sedation |
| Citations | 51 |
| Key findings | A single ketamine infusion significantly reduced depressive symptoms 24 hours after treatment compared with midazolam, with effects appearing to persist up to 14 days. |
Abstract
Objective: Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents.
Methods: In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment.
Results: A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events.
Conclusions: In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.Reprinted from Am J Psychiatry 2021; 178:352-362 with permission from American Psychiatric Association Publishing.