Real-world clinical practice, effectiveness and safety of esketamine nasal spray in major depressive disorder patients: a French prospective cohort (ELLIPSE study)
Pierre-Michel Llorca, Anne Sauvaget, Emilie Olié, Lila Mekaoui, Ludovic Samalin, Maud Rothärmel, Anne-Laure Boitez, Julien Dupin, Clotilde Wicart, Émeline Gaudré-Wattinne, Hugo Lacour, Benjamin Grenier, Bernard Astruc, Bruno Falissard, Pierre De Maricourt
Therapeutic Advances in Psychopharmacology August 1, 2026 DOI: 10.1177/20451253261463652 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective, multicenter, observational cohort study Randomized Peer reviewed |
|---|---|
| Sample size | 200 |
| Population | Adults with unipolar major depressive disorder initiating esketamine in routine clinical practice in France |
| Intervention | Esketamine nasal spray |
| Duration | 12-month follow-up |
| Measures | Montgomery–Åsberg Depression Rating Scale (MADRS) |
| Topics | Depression Esketamine |
| Key findings | Mean MADRS decreased from 31.9 at baseline to 12.4 at month 12 (mean change -17.9). Response and remission rates plateaued at month 2, with response at 55.2% and remission at 33.6%, maintained through month 12. Adverse events occurred in 65.7% of patients, most commonly dissociative states. |
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.