Assessment of patient-reported depression severity in subpopulation of ESCAPE-TRD study: esketamine nasal spray versus quetiapine extended release for treatment-resistant depression.

Objective: ESCAPE-TRD, a randomized phase 3b trial, compares the efficacy and safety of esketamine nasal spray (NS) and extended-release (XR) quetiapine, both in combination with ongoing oral antidepressant (OAD) treatment, among individuals with treatment-resistant depression (TRD). Although prior analyses used the clinician-rated MADRS, the comparative efficacy of esketamine NS vs. quetiapine XR using a patient-reported instrument to assess TRD severity among a subgroup treated according to US label is unknown.

Methods: ESCAPE-TRD data were evaluated using the patient-rated Patient Health Questionnaire-9 (PHQ-9) instrument for individuals receiving treatment consistent with US prescribing information (NCT04338321). The main outcome was remission at weeks 8 and 32. Additional outcomes included response, time to first remission, time to first response, time to confirmed remission, time to confirmed response, and change in PHQ-9 score from baseline.

Results: A significantly higher proportion of individuals in the esketamine NS group than in the quetiapine XR group achieved remission and response at week 8 (remission: 19.3% vs. 12.2%; RD [95% CI]: 7.1% [1.5%, 12.8%]; p = 0.013; response: 49.4% vs. 32.8%, RD [95% CI]:16.6% [9.0%, 24.1%]; p < 0.001). At 32 weeks, a significantly higher proportion of individuals in the esketamine NS group achieved remission and response compared to the quetiapine XR group (remission: 34.8% vs. 18.1%, RD [95% CI]: 16.7% [9.9%, 23.4%]; p < 0.001; response: 58.9% vs. 40.3%, RD [95% CI]:18.5% [10.9%, 26.2%]; p < 0.001).

Conclusion: Using patient-reported PHQ-9 scoring to evaluate ESCAPE-TRD results, esketamine NS produced superior short- and long-term efficacy vs. quetiapine XR among individuals with TRD treated according to US label.