Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy

The purpose of this study is to evaluate the intermediate-term efficacy and tolerability of a multiple-dosing ketamine infusion paradigm for the treatment of medication-refractory major depressive disorder (MDD). The specific aims of the study are: To evaluate the efficacy and tolerability of a multiple-dosing ketamine infusion paradigm (2 infusions per week for 3 weeks) compared to midazolam in adolescents with treatment resistant depression (TRD), . To test these aims we have designed a two-phase trial. The first phase is a 3-week double blind parallel design clinical trial comparing 6 infusions of ketamine compared to 6 infusions of midazolam in 24 adolescents with TRD. The primary outcome of this phase will be Children's Depression Rating Scale (CDRS) score at Day 18. The second phase is a 6-month open phase in which patients who received midazolam and remain depressed with be offered open ketamine treatment (6 infusions over 3 weeks). All participants will be followed weekly for 6 months and tracked for time to relapse. In those who initially responded to ketamine, symptom triggered maintenance infusions will be offered during this 6-month time period. All participants will receive standard of care treatment in addition to experimental procedures, and will be tracked monthly with extensive neurocognitive assessments.