Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders

Intranasal esketamine represents a novel therapeutic option for Treatment-Resistant Depression (TRD). However, its medium-to-long-term risk-benefit profile in real-world clinical practice remains controversial. Limited data is available regarding its effectiveness, particularly in patients who have not responded to electroconvulsive therapy (ECT), which is the focus of this study. We conducted a 6-month observational study investigating intranasal esketamine treatment in the first TRD patients managed at our care centers. We compared outcomes between patients who had not responded to prior ECT and those for whom ECT had not been attempted. The sample comprised 60 patients exhibiting high chronicity (mean episode duration: 41.2 ± 54.7 months) and complexity, with psychiatric comorbidity observed in 37 cases (61.6%). The mean Montgomery-Åsberg Depression Rating Scale (MADRS) score decreased from a baseline of 33.9 ± 7.8 to 15.7 ± 9.6 at 6 months. No significant differences in therapeutic responses were observed in patients who had not responded to ECT during the current episode. This real-world study suggests the opportunity to promptly test intranasal esketamine in ECT refractory subtype of TDR patients.