Ketamine in treatment-resistant depression shows rapid symptom relief, but long-term efficacy, relapse prevention, and routine clinical implementation remain unresolved

Ketamine in treatment-resistant depression centers on a fast-acting antidepressant effect that can reduce symptoms within hours or days in patients who have not benefited from standard therapies. Clinical interest focuses on both intravenous ketamine and related glutamatergic approaches, especially where urgent symptom reduction is needed. Evidence supports short-term efficacy, but important limits remain around durability, maintenance strategies, relapse after discontinuation, safety monitoring, dissociation, abuse liability, and patient selection. Routine psychiatric use therefore depends not only on rapid response rates, but also on clearer protocols for repeated dosing, long-term follow-up, and integration into broader depression care. The wider significance lies in a shift away from monoamine-only models of antidepressant treatment toward mechanisms involving glutamate, synaptic plasticity, and circuit-level change. Ketamine has become both a therapeutic option and a research pathway for understanding faster interventions in severe mood disorders.