Effectiveness and factors associated with esketamine response during the 4-week induction period for treatment-resistant depression: post-hoc analysis of the real-world ESKALE study.
Ludovic Samalin, Maud Rothärmel, Lila Mekaoui, Anne Sauvaget, Clotilde Wicart, Emeline Gaudre-Wattine, Vanessa Cohignac, Andrés Malatesta, Julien Dupin
Journal of Psychiatric Research June 1, 2026 DOI: 10.1016/j.jpsychires.2026.03.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post-hoc analysis of an observational study Peer reviewed |
|---|---|
| Sample size | 128 |
| Population | Patients with treatment-resistant depression |
| Duration | 4-week induction treatment period |
| Topics | Depression Esketamine |
| Keywords | Dissociation Efficacy Observational study |
| Key findings | Depressive symptoms decreased significantly during the first week of esketamine treatment, and early dissociation was associated with a higher likelihood of response at week 1. |
Abstract
In patients with treatment-resistant depression (TRD), the efficacy and tolerance of intranasal esketamine (ESK) spray, alone or combined with oral antidepressants, has been supported by clinical trials and observational studies. The French real-world ESKALE study assessed the benefit of ESK in 157 patients with TRD. In this post-hoc analysis of the ESKALE study we aimed to describe the evolution of depressive symptoms (using the Montgomery Åsberg Depression Rating Scale [MADRS]) and to identify potential factors associated with response during the 4-week induction treatment period. Data from 128 patients were analyzed. The mean MADRS total score (after adjusting) significantly decreased during the first week of ESK treatment by 7.5 points (95% CI: 9.2 to -5.7; p < 0.001) and at W4 by 13.5 points (95% CI: 15.3 to -11.8; p < 0.001). The response rate (MADRS total score reduced by ≥ 50%) continually increased during the 4-week induction treatment period: from 19.4% at W1 to 47.4% at W4. Multivariate analysis identified the occurrence of dissociation during the first week of treatment to be significant factor associated with ESK response at W1 (odds ratio: 3.30 [95% CI: 1.19 to 9.13]; p = 0.021]). No other factors were significantly associated with ESK response at W1 or W4. This post-hoc analysis provides further evidence of a rapid response after ESK initiation in patients with TRD and that early dissociation may play a role in treatment response. However, future research is needed to investigate prognostic factors associated with ESK response in patients with TRD.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 17
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Do the dissociative side effects of ketamine mediate its antidepressant effects? Journal of Affective Disorders February 18, 2014
- Features of Dissociation Differentially Predict Antidepressant Response to Ketamine in Treatment-Resistant Depression Journal of Affective Disorders February 17, 2018
- Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Neuropsychopharmacology May 12, 2023
and 12 more in the library