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A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study.

Patricio Molero, Angela Ibañez, Javier de Diego-Adeliño, Josep Antoni Ramos‐quiroga, Marta García Dorado, Paola M López Rengel, Pilar A. Sáiz

Advances in Therapy May 1, 2025 DOI: 10.1007/s12325-025-03149-z (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational, cross-sectional, retrospective study Peer reviewed
Sample size 196
Population Adults aged 18-74 years with treatment-resistant depression in Spain
Intervention Esketamine nasal spray
Topics Depression Esketamine
Keywords Mental health breakthrough Esketamine therapy Observational study Real-world evidence Remission Response Depression treatment Clinical outcomes
Citations 8
Key findings Esketamine nasal spray produced response or remission in 80.4% of patients during the induction phase and 90% during the maintenance phase, with most adverse events being mild and decreasing over time.

Abstract

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. 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. 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. 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.

Comparable studies

Other cross-sectional and survey studies on esketamine for depression, most cited first.

Study Year Design Participants
Addressing diversity gaps in esketamine clinical trials: a registry-based cross-sectional analysis of sex, race and ethnicity. Participants in interventional esketamine trials with results posted on ClinicalTrials.gov 2026 Registry-based cross-sectional analysis n = 5,116
Mental health professionals' perspective on the use of esketamine in treatment-resistant depression and their motivation to adopt it: a Saudi cross-sectional study. Psychiatrists (of all levels, including those in training) across Saudi Arabia 2026 Cross-sectional study n = 223
Characteristics of patients with major depressive disorder eligible for and prescribed esketamine, treatment outcomes and physician experiences: a physician and patient survey in the United States. Patients with treatment-resistant depression (TRD) or major depression with acute... 2025 Cross-sectional survey n = 914
The perspectives of patients with depression toward esketamine, and the influence of their medication adherence on their viewpoints: a Saudi cross-sectional study. Adults with depression 2025 Cross-sectional study n = 283
Is approving esketamine as an antidepressant for treatment resistant depression associated with recreational use and risk perception of ketamine? Results from a longitudinal and cross-sectional survey in nightlife attendees. UK residents aged 18-34 who attended at least 6 electronic music events in the past year 2022 Longitudinal observational study with a cross-sectional sample n = 2,415

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