DOI: 10.1192/j.eurpsy.2026.11420 ISSN: 0924-9338

Short-term preliminary clinical results from HIPOCRAT-ESK study: a cohort, non-interventional, prospective, real-world study of functional remission in TRD patients treated with Esketamina nasal spray.

T. Caraballo Lopez, M. García Dorado, F. Mora, J. M. Crespo Iglesias, Á. Ibáñez Cuadrado, N. Cardoner Álvarez

Introduction

Approximately up to 55% of patients diagnosed with major depressive disorder (MDD) meet treatment resistant depression (TRD) criteria 1, characterized by a worsened prognosis2,3. In this context, esketamina nasal spray (ESK NS) arises as a novel therapeutic option with a different mechanism of action, based in the regulation of the glutamatergic pathway, directed to enhance brain neuroplasticity4.

Objectives

To report the initial results of HIPOCRAT-ESK, the first real-world, prospective study evaluating functional remission of TRD patients treated with ESK NS based in Spanish clinical practice.

Methods

HIPOCRAT-ESK is a cohort, non-interventional, prospective, real-world study evaluating functions remission as a primary endpoint in TRD patients treated with ESK NS as per the Spanish clinical practice. Total sample consists in 300 TRD patients with a prospective follow-up of 12 months. It evaluates clinical evolutions using MADRS, SDS, PHQ-9 and EQ-5D-5L scales. We present the short-term preliminary results (first 25% of the total sample recruited) focusing on clinical evolution.Basal sociodemographic and safety profile is included in the analysis.

Results

83 patients were included in the intention to treat analysis and 95 in the safety analysis. The sample was severely depressed, with a basal MADRS total score of 37 points. Presence of TRD and psychiatric comorbidities was high, especially anxiety disorder and borderline personality disorder (10.84% each). Real-world use of ESK NS achieved positive short -term clinical results. Patients achieved mean clinically meaningful improvement in MADRS mean total score, as soon as in the second treatment administration, with sustained improvements during the induction phase (mean total MADRS score decrease of 12.55 points vs basal). Clinical response and clinical remission were achieved by 21.43% and 7.14% of patients, respectively, by the end of induction phase. Patients in HIPOCRAT-ESK were included in different TRD stages based in the number of prior failed AD therapies. The analysis showed that, therapeutic inertia and treatment chronicity decreases the rates of clinical and remission response (Table 3). Key safety findings were aligned with already published data for ESK NS.

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Conclusions

HIPOCRAT-ESK is the first prospective, real-world evidence study aiming to evaluate functional remission in TRD patients treated with ESK NS as primary endpoint. Preliminary short-term analysis shows promising efficacy results, with clinical improvements observed as soon as second administration session and sustained over the induction phase

Disclosure of Interest

T. Caraballo Lopez Employee of: Full-time employee, M. García Dorado Employee of: Full-time employee, F. Mora Grant / Research support from: Research support, Consultant of: Consultant for Johnson & Johnson, J. M. Crespo Iglesias Grant / Research support from: Research support recieved form Johnson & Johnson, Consultant of: Act as a consultant for Johnson & Johnson, Á. Ibáñez Cuadrado Grant / Research support from: Recieved research support from Johnson & Johnson, Consultant of: Acts as a consultant for Johnson and Johnson, N. Cardoner Álvarez Grant / Research support from: Recieves research support from Johnson & JOhnson, Consultant of: Acts as a consultant for Johnson & Johnson

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