(72) Efficacy of Ketamine for Treatment of Adolescent Medication-Refractory Major Depressive Disorder and Anxiety Disorders

The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2)... [ view full abstract ]

The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety disorder, panic disorder, generalized anxiety disorder and/or separation anxiety disorder). We will conduct a crossover trial in which as many as 36 adolescents (18 with MDD and 18 with anxiety disorders) will be given a single infusion of ketamine (study drug) or midazolam (active control). MDD symptoms and anxiety symptoms will be monitored over a two-week period. If applicable, comorbid school refusal symptoms will also be monitored over a two-week period for both cohorts. A 2-week washout period will be required between infusion doses. Our primary outcomes will be 1) improvement in MDD symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial and 2) improvement in the anxiety symptoms (measured by the Multimodal Anxiety Scale for Children (MASC) acute physical symptoms subscale) for the cohort of subjects enrolled in the anxiety disorders arm of the trial. As secondary outcomes, we are also proposing to (1) more comprehensively assess suicidal ideation as an additional efficacy outcome in the trial, (2) measure ketamine’s effects on symptom constructs associated with suicidal ideation or behavior, including anxiety, anhedonia and hopelessness, (3) examine ketamine’s effects on school-refusal behavior (SRB) that is associated with anxiety and depression and examine ketamine’s effects on frontal neural systems associated with suicidal ideation and behavior as well as anxiety using functional magnetic resonance imaging (fMRI) and a behavioral task that has previously demonstrated findings associated with suicide attempts in adolescents with mood disorders.