Ketamine for Treatment-Resistant Depression in Adolescents: Hope or Risk?

Abstract

Treatment-resistant depression (TRD) in adolescents remains a major clinical challenge because of the limited efficacy of conventional antidepressants and the high risk of suicidal behavior. Ketamine has emerged as a rapidly acting antidepressant with a unique glutamatergic mechanism, promoting neuroplasticity and reducing neuroinflammation. Clinical studies demonstrate significant symptom improvement, often within 24 hours, although the effects are generally short-lived. Concerns remain regarding dissociative and cardiovascular adverse effects, abuse potential, and the uncertain long-term impact on the developing brain. Background: Adolescent TRD is associated with severe functional impairment and poor response to standard treatments, highlighting the need for faster-acting therapeutic options. Aim: To review the efficacy, mechanisms of action, and safety of ketamine in adolescents with TRD. Materials and methods: A narrative review of the literature on ketamine pharmacology, clinical efficacy, and safety in adolescent TRD was conducted. Summary: Ketamine produces rapid antidepressant effects through modulation of glutamatergic neurotransmission and enhancement of neuroplasticity. Current evidence supports short-term efficacy, while long-term outcomes remain uncertain. Conclusions: Ketamine is a promising option for selected adolescents with TRD requiring rapid symptom relief, but its use should remain limited to specialized clinical settings until further evidence confirms its long-term safety and efficacy.