Esketamine nasal spray in real-world care: depression scores fell over 4 weeks

The question

How quickly do depression symptoms change in the first four weeks of intranasal esketamine treatment for treatment-resistant depression, and can anything predict who responds?

What they did

Researchers re-analyzed data from ESKALE, a French real-world study of 157 people with treatment-resistant depression (depression that has not improved with previous antidepressants) who received esketamine nasal spray, on its own or alongside oral antidepressants. Data from 128 of those patients were included in this analysis. Depression was measured with the Montgomery Asberg Depression Rating Scale (MADRS), a clinician-rated symptom score, during the four-week starting (induction) phase. The team also tested whether patient or treatment characteristics predicted who improved.

What they found

Average MADRS scores dropped by 7.5 points in the first week (95% confidence interval 9.2 to -5.7; p < 0.001) and by 13.5 points by week 4 (95% CI 15.3 to -11.8; p < 0.001). The response rate, defined as at least a 50% drop in MADRS score, rose from 19.4% at week 1 to 47.4% at week 4. Experiencing dissociation (a temporary sense of detachment from oneself or surroundings) during the first week was linked to a higher chance of responding at week 1 (odds ratio 3.30; 95% CI 1.19 to 9.13; p = 0.021). No other factor was significantly linked to response at week 1 or week 4.

The fine print

This was an observational study without a placebo or comparison group, so improvement could partly reflect the natural course of illness, other treatments or expectation. It is a post-hoc analysis, meaning the questions were asked after the data were collected, which increases the chance of a finding by luck. Follow-up covered only the four-week induction phase, and 29 of the original 157 patients were not included in this analysis. This summary is based on the abstract only.

What it means

In routine care, people with treatment-resistant depression showed rapid and continuing drops in depression scores over four weeks of esketamine, with just under half meeting the response threshold; early dissociation was linked to early response, but this link needs testing in better-controlled studies.

Evidence grade: Low. This is a post-hoc analysis of an observational real-world study with no control or comparison group, so improvement cannot be attributed to the drug alone.

This summary is based on the study’s published abstract.