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 (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.