Esketamine nasal spray beat quetiapine on quality-of-life measures in hard-to-treat depression

The question

Beyond reducing depression scores, does esketamine nasal spray improve patients’ day-to-day quality of life more than an add-on antipsychotic in treatment-resistant depression?

What they did

ESCAPE-TRD was a 32-week randomized phase IIIb trial in people with treatment-resistant depression, meaning depression that has not responded to at least two antidepressants. Participants kept taking their existing antidepressant (an SSRI or SNRI) and were randomly assigned to add either esketamine nasal spray (336 people) or extended-release quetiapine (340 people). The researchers tracked self-reported depression symptoms (PHQ-9) and four health-related quality-of-life questionnaires covering areas such as emotional role, social functioning, mobility and daily activities.

What they found

By week 32, 34.5% of the esketamine group reached remission on the PHQ-9 (a score of 4 or less) compared with 18.2% of the quetiapine group (odds ratio 2.39, 95% CI 1.67 to 3.41, p<0.0001), and they got there sooner. On the SF-36 questionnaire, the “Role Emotional”, “Mental Health” and “Social Functioning” areas improved significantly more with esketamine (p<0.05), ending close to general population levels. A meaningful improvement on the Quality of Life in Depression Scale was reached by 60.7% of the esketamine group versus 41.8% of the quetiapine group (odds ratio 2.16, 95% CI 1.59 to 2.94, p<0.0001). More esketamine-treated patients also reported “no problems” across all EQ-5D-5L domains at week 32 (p<0.05).

The fine print

The abstract does not say whether participants or raters knew which treatment was given, and an active comparator trial like this is difficult to blind, which can inflate self-reported benefits. Quality-of-life measures were secondary to the trial’s main symptom outcomes, and follow-up stopped at 32 weeks, so longer-term effects are unknown. No side-effect or safety data are reported in this abstract. This summary is based on the abstract only.

What it means

In this trial, adding esketamine nasal spray to an antidepressant was linked to larger gains in everyday functioning and wellbeing than adding extended-release quetiapine, not just lower symptom scores.

Evidence grade: Moderate. A large multicentre randomized trial, but these are quality-of-life outcomes reported alongside the main results, and the abstract does not describe blinding or a placebo group.

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