Treatment-resistant depression (TRD) occurs when a patient fails to respond to at least two adequate antidepressant trials, and it imposes a greater social and economic burden than non-resistant depression. A committee of ten Spanish psychiatrists reviewed recent literature and developed consensus statements on TRD definitions, clinical response criteria, and the role of intranasal esketamine, which improves neuroplasticity and synaptogenesis. They highlighted therapeutic inertia—its causes and consequences—and produced a treatment algorithm that includes specific response evaluation steps to avoid inertia and ensure adequate treatment. This is the first Spanish consensus on theoretical aspects of TRD and intranasal esketamine's place in therapy.
Treatment-resistant depression (TRD) patients have often been excluded from antidepressant drug trials, leaving unclear clinical guidance. Intranasal esketamine, a non-monoaminergic treatment that modulates the glutamatergic system to improve neuroplasticity, offers a new option. A Spanish committee of nine psychiatrists expert in TRD reviewed literature from 2014 to 2024 and developed a consensus on practical management. They recommend a treatment algorithm for TRD with intranasal esketamine, including guidance for patients with psychiatric comorbidities and for those who show less than a 50% symptom reduction after the first induction phase. Treatment should occur at the patient's usual mental health center, with dose optimization and flexible management based on clinical progress. This is the first such consensus in Spain.