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.
In a naturalistic study across four Madrid hospitals, 55% of 65 patients with treatment-resistant depression who received esketamine as an augmentation treatment achieved remission over follow-up. Among those who completed the standard protocol, remission rates rose to 67%, and to 70% for those receiving more than 19 administrations. Remission was associated with completing the standard protocol and with the absence of dissociative symptoms. Receiving more than 19 esketamine administrations increased the odds of remission. Adverse effects did not affect treatment continuation.
In a six-month naturalistic study of 62 patients with treatment-resistant depression and high suicide risk, those receiving intranasal esketamine showed faster and greater reductions in suicidal thoughts and depressive symptoms compared to those receiving alternative pharmacological treatments. The number needed to treat to prevent one case of high suicide risk was 1.35. Functional improvement was similar between groups. The findings support esketamine as a rapid-acting option in real-world, closely monitored care.