Jennifer Dwyer, M.D., Ph.D.

Fellow In Depression

Project Details

Mentors

Michael Bloch, M.D., M.S.
Gerard Sanacora, M.D., Ph.D.


Institution

Yale University


Project

Ketamine for severe adolescent depression: intermediate-term safety and efficacy


PROJECT TITLE

Ketamine for severe adolescent depression: intermediate-term safety and efficacy

PROJECT SUMMARY

Nearly one in four adolescents will experience major depressive disorder, and suicide is the 2nd leading cause of death in this age group. Forty percent of adolescents with depression fail to respond to initial treatment with selective serotonin reuptake inhibitors. Of this resistant population, nearly half remain depressed despite alternate medication and psychotherapy. Thus, better treatments are urgently needed. Ketamine, a glutamatergic modulator, has generated considerable excitement in psychiatry, as a single infusion produces potent (effect size of 1.2), rapid (<1 day), but ephemeral (<7 days) antidepressant effects in adults with treatment resistant depression (TRD). Repeated infusion paradigms significantly extend the duration of effectiveness. We are among the first to examine ketamine’s short-term antidepressant effects in adolescents with TRD in a clinical trial, and have shown intermediate-term effectiveness of a repeated dosing paradigm in an adolescent case report. Ketamine has a strong pediatric safety record when given as single doses under appropriately monitored conditions, but the effects of repeated ketamine treatments are not well characterized. Here we have proposed a randomized controlled clinical trial to systematically address the urgent question of repeated ketamine’s effectiveness and neurodevelopmental impact over the intermediate term in adolescents with TRD. We hypothesize that a multiple infusion paradigm will extend antidepressant effects significantly beyond that of a single infusion, and that the paradigm will be well-tolerated medically, psychiatrically, and neurocognitively over 6 months. We anticipate this study providing important new evidence for a novel pharmacological intervention for adolescents with TRD.

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