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.

In patients with treatment-resistant depression, depressive symptoms improved rapidly during the first four weeks of intranasal esketamine treatment. Among 128 patients in a French real-world study, the average depression rating score fell by 7.5 points after one week and by 13.5 points after four weeks. The proportion of patients whose score dropped by at least half rose from 19.4% at week 1 to 47.4% at week 4. Experiencing dissociation during the first week was linked to a threefold higher chance of response at week 1, but no other factors predicted response. The findings suggest early dissociation may play a role in treatment response, but more research is needed on prognostic factors.

Study at a glance

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.