Real-world clinical practice, effectiveness and safety of esketamine nasal spray in major depressive disorder patients: a French prospective cohort (ELLIPSE study).

Abstract

Background: Major depressive disorder (MDD) is highly prevalent and associated with significant disability and mortality. Treatment-resistant depression (TRD), defined as inadequate response to ⩾2 antidepressant lines, remains a major therapeutic challenge. Esketamine nasal spray, approved in 2019 for TRD, demonstrated efficacy and safety in randomized trials, but real-world evidence remains limited.

Objectives: The ELLIPSE study aimed to describe patient characteristics, treatment patterns, and 12-month outcomes of esketamine in routine clinical practice in France.

Design: ELLIPSE was a prospective, multicenter, observational cohort study including adults with unipolar MDD initiating esketamine between Dec 2021 and Jul 2023, followed for 12 months.

Methods: Data were collected via standardized clinical assessments. Effectiveness was evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS). Response was defined as ⩾50% MADRS reduction; remission as MADRS ⩽ 10.

Results: A total of 200 patients (mean age 46.6 years; 56.5% female) were enrolled; 97.5% met TRD criteria. Median esketamine exposure was 4.5 months. Mean MADRS decreased from 31.9 at baseline to 12.4 at month 12 (mean change -17.9; 95% CI: -21.6 to -14.2). Response and remission rates reached a plateau at month 2, where the response rate was 55.2% and the remission rate was 33.6%, maintained up to month 12. Adverse events (AEs) occurred in 65.7% of patients, most commonly dissociative states (28.0%) and transient blood pressure increases (11.6%).

Conclusion: This real-world study in patients with treatment-resistant depression, including those with comorbidities/prior suicide attempts, showed clinically relevant improvement from month 2, sustained through 12 months. Dissociative symptoms were the most frequent treatment-related AE.