TOPLINE:

Intranasal esketamine was associated with rapid antidepressant effects in patients with treatment-resistant depression (TRD), with a 7-point reduction in symptoms at week 1, new findings from the real-world ESKALE study showed. Additionally, early dissociation was linked to treatment response in the first week.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the real-world, multicenter ESKALE study, which enrolled patients with TRD treated between 2019 and 2021 in France.
• Overall, 128 patients (mean age, 49 years; 65% women) who received at least one dose of esketamine and completed Montgomery-Åsberg Depression Rating Scale (MADRS) assessments at baseline and at least once between week 1 and week 4 were included.
• Before treatment initiation, patients had a median of three major depression episodes and had received a median of six prior treatments.
• Outcomes included changes in depressive symptom scores on the MADRS and treatment response rates, defined as a reduction of at least 50% in total MADRS score from baseline during the 4-week induction period. Additional analyses evaluated factors such as dissociation, which is characterized by depersonalization, derealization, perceptual detachment, an altered sense of self or surroundings, emotional numbing, or dissociative amnesia.

TAKEAWAY:

• Esketamine was associated with a significant decrease in MADRS total score from baseline, with an adjusted mean reduction of 7.5 points at week 1 and 13.5 points at week 4 (P < .0001 at both timepoints).
• Response rates progressively increased across weeks — from 19% at week 1 to 27% at week 2, 33% at week 3, and 47% at week 4.
• The occurrence of dissociative events during the first week was significantly linked to response at week 1 (odds ratio, 3.3; P = .02), whereas severe depression only showed a trend toward association (P = .05).
• No factors, including dissociation, were significantly linked to esketamine response at week 4.

IN PRACTICE:

“This post hoc analysis provides further evidence of a rapid response after [esketamine] initiation in patients with TRD and that early dissociation may play a role in treatment response,” the investigators wrote. 

“However, future research is needed to investigate prognostic factors associated with [esketamine] response” in this patient population, they added.

SOURCE:

The study was led by Ludovic Samalin, MD, PhD, Clermont-Ferrand University Hospital, University of Clermont Auvergne, Clermont-Ferrand, France. It was published online on March 10 in the Journal of Psychiatric Research.

LIMITATIONS:

MADRS scores were not systematically recorded between weeks 1 and 4, with 33%-39% of scores missing at each visit, resulting in a smaller, selected sample. Dissociation was reported by physicians in real-world settings rather than assessed using standardized scales. As esketamine differs pharmacologically from traditional antidepressants, standard assessment tools may not have fully captured its unique subjective and experiential effects. Additionally, reliance on existing data limited the evaluation of all potential prognostic factors.

DISCLOSURES:

The study was funded by Janssen-Cilag France. Several investigators reported having financial or other ties with various organizations and pharmaceutical companies including Janssen-Cilag France. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.