A systematic review of 16 studies (22 reports) examined ketamine and esketamine for mood disorders, anxiety, and suicidality in youth up to 19 years old. Studies included case studies, observational studies, and randomized trials. Immediate improvements in depression, anxiety, and suicidality were reported, with benefits lasting weeks to months. Ketamine was well-tolerated; common side effects were dizziness, nausea, and mild dissociation, and transient hemodynamic changes resolved without intervention. The evidence suggests ketamine is safe and may be effective, but further randomized trials are needed.
MDMA-assisted psychotherapy (MDMA-AP) may soon be approved for adults with PTSD, but adolescents also commonly suffer from PTSD and current treatments have limitations. As an adjunct to therapy, MDMA may reduce avoidance, strengthen therapeutic alliance, enhance extinction learning and trauma reappraisal. Adaptations for adolescents include reinforcing motivation, building a strong therapeutic alliance, adding emotion and behavior management techniques, using more directive exposure methods during sessions, supporting concomitant challenges, and involving family. Potential risks include physical and psychological side effects, toxicity, misuse, and ethical issues. Clinical trials are needed to determine safety and efficacy for adolescents rather than off-label use or extrapolating from adult studies.