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.
Intranasal esketamine is a newer treatment for Treatment-Resistant Depression (TRD), but its long-term benefits in real-world settings remain uncertain. A 6-month observational study of 60 highly chronic and complex TRD patients (average episode length 41.2 months, 61.6% with psychiatric comorbidity) found that depression scores (MADRS) dropped from an average of 33.9 at baseline to 15.7 at 6 months. Patients who had not responded to prior electroconvulsive therapy (ECT) showed no significant difference in therapeutic response compared to those who had not tried ECT. The findings suggest that intranasal esketamine may be worth testing promptly in TRD patients who have not responded to ECT.