Project Details

Efficacy of rapid-acting NMDA antagonist for treatment of adolescent depression

Jennifer Dwyer, MD, PhD

Summary

BACKGROUND: Major depressive disorder (MDD) afflicts nearly 1 in 5 adolescents, and suicide, a complication of inadequately treated depression, is the 2nd leading cause of death in this age group. 40% of adolescents with MDD fail to respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and of that resistant population, nearly half fail to respond to alternate medication and psychotherapy. GAP: In adults, sub-anesthetic doses of the NMDA antagonist, ketamine, show potent, rapid antidepressant and anti-suicidal properties in treatment-resistant MDD (at least a 50% improvement in depressive symptoms within 1 day of treatment). While case reports suggest that ketamine may also alleviate treatment-resistant adolescent MDD, there are no published prospective, randomized controlled trials to guide clinicians regarding ketamine use in this population. HYPOTHESIS: We hypothesize that ketamine will be tolerated well medically and psychiatrically in adolescents with treatment-resistant MDD; we expect ephemeral side effects, similar in severity and frequency to those reported in adults. We also hypothesize that ketamine infusion will significantly reduce depressive symptoms, manifested by a reduction in MADRS score versus placebo at 1 day following infusion. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover trial of intravenous ketamine (0.5mg/kg over 40 minutes) in 17 adolescents with SSRI-resistant MDD over 4 weeks. We included male and non-pregnant females adolescents (13-17yo) who met criteria for MDD (via Children’s Depression Rating Scale >40) and who have failed at least one adequate trial of a traditional antidepressant. RESULTS: Ketamine and the active placebo, midazolam, were well tolerated. Ketamine significantly reduced depression scores at 1 day following treatment compared to midazolam in adolescents with treatment-resistant depression. IMPACT: These positive short-term findings have lead to the design of a larger, more definitive trial examining the safety and effectiveness of ketamine infusions over the intermediate term, which is slated to begin within the next 3 months. While this additional testing of safety and effectiveness in the pediatric populations is needed, we anticipate that ketamine could become a valuable tool in the pediatric pharmacologic arsenal within 5-10 years. Given the significant health burden of adolescent MDD and suicide, this novel treatment could be very impactful to overall child health. Website Link: https://clinicaltrials.gov/ct2/show/NCT02579928

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