This study aims to assess the tolerability and immediate efficacy of a single ketamine infusion in treating adolescents with medication-resistant major depressive disorder (MDD) and/or anxiety disorders, including social anxiety, panic disorder, generalized anxiety, and separation anxiety. In a crossover trial, up to 36 adolescents will be randomly administered either ketamine or midazolam (active control). The trial will monitor changes in MDD and anxiety symptoms over two weeks, with additional attention to comorbid school refusal symptoms in both groups. A two-week washout period is mandated between doses. The primary measures of success include improvement in MDD symptoms, evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS), and reduction in anxiety symptoms, assessed using the Multimodal Anxiety Scale for Children (MASC). This study is pivotal in exploring innovative treatment options for young individuals facing challenges with traditional depression and anxiety therapies.