Introduction: The INTEGRATE study aimed to provide information on the use, effectiveness, and safety of esketamine nasal spray (ESK-NS) for the treatment of treatment-resistant depression (TRD) in real-world practice in Spain.
Methods: This was an observational, cross-sectional, retrospective study conducted in adults aged 18-74 years who met the criteria for TRD. The weekly impact of ESK-NS on depressive symptoms was evaluated by clinical judgment using four categories (nonresponse, response, remission, not available). The onset of action 24 h after administration was also evaluated. Information on adverse events was collected from the medical records.
Results: We included 196 patients, of whom 189 were considered evaluable; the mean (SD) number of previous episodes was 3.7 (3.0). According to the investigator's judgment, 152 (80.4%) of 189 patients were in response or remission in the induction phase, and 54 (90%) of 60 during the maintenance phase. The proportions of patients in remission were 9.5%, 18.7%, and 38.3% during the induction, optimization, and maintenance phases, respectively. Fifty-three (28.0%) patients experienced an improvement in depressive symptoms within the first 24 h after the first administration of ESK-NS. Most adverse events reported with ESK-NS were mild and did not require any action with the study drug; the number of adverse events decreased over time, especially during the first 4 weeks.
Conclusion: Consistent with the available evidence, the results of this study indicate that ESK-NS is an effective and safe option to consider within the therapeutic algorithm for TRD.
Keywords: Esketamine nasal spray; Observational study; Real-world evidence; Remission; Response; Treatment-resistant depression.
Treatment-resistant depression (TRD) is a type of major depressive disorder that occurs when at least two different first-line antidepressants fail to manage the condition during a depressive episode. Esketamine nasal spray (ESK-NS) is the first drug approved by the US and European health authorities for adults with TRD in combination with an oral antidepressant. Its efficacy was demonstrated in randomized clinical trials which are the standard for the evaluation of drugs, but which usually include patients not fully representative of those seen in clinical practice. The INTEGRATE study was aimed to evaluate the effectiveness and safety of ESK-NS in clinical practice. We included 189 evaluable patients with TRD. According to the investigator’s judgment, 152 (80.4%) of 189 patients were in response (i.e., relevant improvement of symptoms) or remission (i.e., almost elimination of symptoms) within the first 4 weeks of treatment, and 54 (90%) of 60 after at least 9 weeks of treatment. Fifty-three (28.0%) patients had an improvement in depressive symptoms within the first 24 h after the first administration of ESK-NS. Most adverse events reported with ESK-NS were mild and did not require any action with the study drug; the number of adverse events decreased over time, especially during the first 4 weeks. Consistent with information from randomized clinical trials, these results indicate that ESK-NS is an effective and safe option to consider when deciding what treatment to select for TRD.
© 2025. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.