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) 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.