Project Details

Early Career

Status: Funded - Closed

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

Jennifer Dwyer, MD, PhD


BACKGROUND: Major depressive disorder (MDD) afflicts nearly 1 in 4 adolescents, and suicide, a complication of inadequately treated depression, is the 3rd 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 CDRS-R score versus placebo at 1 day following infusion.

METHODS: We are conducting a randomized, double-blind, placebo-controlled crossover trial of intravenous ketamine (0.5mg/kg over 40 minutes) in 18 adolescents with SSRI-resistant MDD over 4 weeks. We will include male and non-pregnant females adolescents (13-17yo) who meet criteria for MDD (via Children’s Depression Rating Scale >40) and who have failed at least one adequate trial of a traditional antidepressant.

RESULTS: Pending

IMPACT: We expect that positive findings in this trial would lead to a larger, more definitive trial within the next 2-3 years, and 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:


Ketamine as a Treatment for Adolescent Depression: A Case Report