Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders
The European Journal of Psychiatry – March 07, 2026
Source: OpenAlex
Summary
Intranasal esketamine shows promise as a treatment for patients with Treatment-Resistant Depression (TRD), particularly those unresponsive to electroconvulsive therapy (ECT). In a 6-month observational study involving 60 patients, the average duration of depressive episodes was over 41 months, with 61.6% experiencing psychiatric comorbidities. The mean depression score significantly dropped from 33.9 to 15.7, indicating substantial improvement. Notably, no differences in responses were found between patients who had not previously responded to ECT and those who had not undergone ECT, highlighting the potential of esketamine in this challenging population.
Abstract
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.