This randomised, double-blind, placebo-controlled Phase III trial (n=60) will investigate the efficacy and safety of subcutaneous ketamine (35-70mg/70kg, twice weekly for four weeks) as an add-on treatment for adolescents experiencing a major depressive episode with suicidal ideation and/or behaviour.
Led by Dr Sheila Caetano at the Federal University of São Paulo, the study targets adolescents aged 12 to 19 who are already undergoing standard treatment for depression but continue to exhibit significant depressive symptoms and suicide risk.
Participants will be randomly assigned to receive either ketamine or an active placebo (1 mg midazolam) administered subcutaneously. All treatments will be given under medical supervision, and dose adjustments will be permitted based on the patient’s response and tolerability. The trial will evaluate rapid antidepressant effects within 24 hours of the first dose, using the Montgomery–Åsberg Depression Rating Scale (MADRS) and Columbia Suicide Severity Rating Scale (C-SSRS) to measure symptom remission and reductions in suicidal thoughts and behaviours. This study aims to provide evidence for ketamine as a fast-acting intervention in a highly vulnerable youth population.
Trial Details
Depression affects approximately 8% of adolescents, with an estimated 60% showing inadequate response to current standard treatments. Ketamine, a glutamatergic modulator, has demonstrated efficacy in adults with treatment-resistant depression and has shown promising preliminary results in adolescent populations. This Phase III, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of subcutaneous ketamine as an adjunctive treatment for adolescents experiencing a major depressive episode with active suicidal ideation and/or behavior. Participants will be randomized into two parallel groups to receive either subcutaneous ketamine (0.5 to 1 mg/kg) or an active placebo (1 mg midazolam diluted in 5 ml of 0.9% saline), administered twice weekly for four weeks. All participants will continue their usual treatment regimens. A two-week post-treatment follow-up period will be conducted to assess the persistence of effects and monitor safety outcomes. Clinical assessments include diagnostic and symptom severity scales validated for pediatric populations. The efficacy will be primarily measured by depression remission and response, while safety will be assessed via adverse event monitoring and clinical examination. The trial will include 30 participants per group, providing 80% power to detect a clinically significant difference of 8.7 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) between groups.Trial Number NCT06957704
Sponsors & Collaborators
University of São PauloThe University of São Paulo has been conducting research with psychedelics for many years, with a focus on ayahuasca given its traditional use in Brazil.