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 Peer reviewed DOI: 10.1016/j.jpsychires.2026.03.011 via PubMed
Summary
In patients with treatment-resistant depression, intranasal esketamine treatment led to a significant reduction in depressive symptoms over four weeks. The mean score on the Montgomery Åsberg Depression Rating Scale decreased by 7.5 points in the first week and by 13.5 points by week four. The response rate increased from 19.4% at week one to 47.4% at week four. Early dissociation was identified as a factor associated with response to treatment.
Study at a glance
| Design | observational study |
|---|---|
| Sample size | 128 |
| Population | patients with treatment-resistant depression |
| Key finding | Intranasal esketamine significantly reduced depressive symptoms in patients with treatment-resistant depression over four weeks. |
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.