Intranasal esketamine, combined with an antidepressant, significantly reduced depressive symptoms in patients with severe treatment-resistant depression. In a retrospective study of 71 patients (70% women, 85% with work disability), Montgomery-Asberg depression rating scale scores dropped from a mean baseline of 38.27 at 28, 90, and 180 days. Side effects were common but mostly mild and temporary. Patients who also received psychotherapy had lower depression scores at 90 and 180 days than those who did not. The authors argue that pharmacological treatment for treatment-resistant depression should be integrated with psychotherapy, social support, and family interventions to optimize outcomes.
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.