Ketamine in Adolescents With Treatment-Resistant Depression
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will test the use of ketamine for treatment of depression in adolescents that have
      not responded to other treatments. We will also examine neurobiological mechanisms of
      treatment.
    

Detailed description: 
      Depression frequently emerges during adolescence and is associated with severe outcomes.
      Current interventions do not lead to remission for many adolescents. Treatment-resistant
      depression (TRD) in adolescence is an ominous prognostic indicator for a lifetime of
      suffering and increased risk for suicide. Efforts should be directed toward novel
      interventions that could alter this perilous course. Theoretically, restoration of healthy
      development during this critical window would substantially improve outcomes over the
      lifespan.

      Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type
      glutamate receptor that has long been used for induction and maintenance of anesthesia in
      children and adults, and recently has been investigated for its rapid antidepressant effects.
      Randomized, double-blind, saline-controlled trials in adults with TRD have demonstrated that
      a single, subanesthetic infusion of intravenous (IV) ketamine at 0.5 mg/kg over 40 minutes
      can produce a rapid (within 2 hours) antidepressant response (Ibrahim et al., 2011; Zarate et
      al., 2006). Recent evidence suggests that serial doses of ketamine may be even more effective
      and may lead to more prolonged remission (aan het Rot et al., 2010; Murrough et al., 2012).
      Our current research at using serial dosing of IV ketamine among adult veterans with TRD over
      a 2-week period has shown promising results, with a response rate of 92% among the 12
      participants to date.

      No results from any studies examining effectiveness of either single-dose or serial-dose
      ketamine have yet been published in adolescents with TRD. Because of the ongoing
      neurodevelopment in adolescence, which is thought to confer enhanced neuroplasticity, it is
      possible that adolescents with TRD could show greater responses and more sustained remission
      than adults with TRD. The biological mechanisms of depression impacted by ketamine are only
      now being uncovered in adults (Zarate et al., 2013). Characterization of the neural
      mechanisms underlying ketamine response or non-response in adolescents with TRD will
      represent a significant advance. The specific aims of this preliminary study are as follows:

      Aim #1: To determine the efficacy of repeated-dose subanesthetic IV ketamine among adolescent
      patients with TRD.

      Hypothesis: Based on previous results in adults with TRD, we predict that response rates will
      improve over the course of six treatments of ketamine.

      Aim #2: To explore durability of antidepressant response to repeated dose of IV ketamine in a
      4-week observational period.

      Hypothesis: Based on the inherent neuroplasticity in adolescence due to ongoing
      neurodevelopment, adolescents may show a more durable clinical response than has been seen in
      adults.

      Aim #3: To study the neurobiological mechanisms of response to ketamine. We will examine
      relevant biological systems using several different brain imaging indices and measures of
      intracellular functioning from peripheral blood.
    

Intervention name(s): Ketamine
Intervention type(s): Drug
Intervention description(s): IV infusions of 0.5mg/kg of Ketamine hydrochloride over a 40-minute infusion period. Participants will receive a total of 6 doses over a 2-week period.
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Treatment-resistant