The Efficacy and Safety of Esketamine Nasal Spray Versus Quetiapine Extended Release Over 32 Weeks in Patients With Treatment-Resistant Depression: A Subgroup Analysis of the ESCAPE-TRD Study

Abstract: Objective: ESCAPE‑TRD (NCT04338321), a randomized, open-label, rater-blinded, trial demonstrated benefits for esketamine nasal spray (ESK) versus quetiapine extended release (QXR) for acute and maintenance treatment of adult patients, aged 18-64 years, with treatment-resistant depression (TRD). This subgroup analysis assesses patients who were treated/dosed according to US prescribing information (USPI). Methods: Patients were randomly assigned to either flexibly dosed ESK or QXR, both in combination with an ongoing oral antidepressant. Group differences for remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤10) and response (≥50% improvement in MADRS total score or MADRS ≤10) were analyzed using a Cochran-Mantel-Haenszel test. MADRS change from baseline between arms was analyzed using mixed models for repeated measures. Treatment-emergent adverse events (TEAEs) leading to discontinuation are summarized descriptively. Results: Patients receiving treatment inconsistent with USPI were excluded from this analysis (n=40). Among 636 included patients (ESK, n=316; QXR, n=320), significantly more ESK-treated patients achieved remission starting at week 8 (28.3% vs 18.6%; P=0.005) through week 32 (55.7% vs 36.3%; P 0.001), compared with QXR-treated patients. Similarly, a significantly higher proportion of ESK-treated patients achieved response starting at day 15 (P=0.002) through week 32 (P 0.001), compared with QXR-treated patients. MADRS scores significantly improved with ESK versus QXR at each visit from day 8 onwards. Fewer ESK-treated patients (4.5%) discontinued treatment because of TEAEs versus QXR-treated patients (10.1%). Conclusions: Consistent with the primary analysis, results from this subgroup analysis demonstrated that ESK improves short- and long-term outcomes compared with QXR in patients with TRD treated according to USPI.Short Description: This subgroup analysis from ESCAPE-TRD (NCT04338321) compared efficacy and safety of esketamine nasal spray (ESK) versus quetiapine extended release (QXR), both in combination with an oral antidepressant, in patients with treatment-resistant depression treated/dosed according to US prescribing information. Results indicated that patients treated with ESK had significantly higher proportions achieving response and remission and improved Montgomery-Åsberg Depression Rating Scale total scores over time, and lower rates of treatment discontinuation compared with patients treated with QXR.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC