Weight and Metabolic Changes in Patients Treated With Esketamine Nasal Spray Versus Quetiapine Extended Release: A Post Hoc Subgroup Analysis of the ESCAPE-TRD Study
Objective: To describe weight and metabolic changes associated with esketamine nasal spray (ESK) versus quetiapine extended release (QXR) treatment in patients with treatment-resistant depression in ESCAPE-TRD (NCT04338321) and the impact on study outcomes.
Methods: This is a post hoc subgroup analysis of patients treated with ESK or QXR according to US prescribing information, both in conjunction with an ongoing oral antidepressant. Patients were assessed overall and stratified by body mass index (BMI) category. Weight-related treatment-emergent adverse events (TEAEs) and changes in weight and BMI from baseline were summarized. Metabolic changes were also assessed using clinical laboratory values for cholesterol, triglycerides, and glucose. Efficacy was evaluated using Montgomery-Åsberg Depression Rating Scale (MADRS) total scores.
Results: This analysis included 630 patients (ESK, n=316; QXR, n=314). Fewer patients treated with ESK than with QXR reported treatment-emergent weight gain (2.9% vs 12.3%). Treatment-emergent weight gain led to treatment discontinuation in 1.6% (n=5) of QXR-treated patients (none in the ESK group). QXR-treated patients had significant increases in weight and BMI, and a higher proportion of patients experienced clinically significant weight gain (≥7% increase) than ESK-treated patients (19.9% vs 6.4%; P < 0.001). At week 32, QXR-treated patients experienced a significant increase in mean total and low-density lipoprotein cholesterol levels compared with ESK-treated patients (P < 0.05). Regardless of baseline BMI category, ESK-treated patients had greater improvement in MADRS total scores compared with QXR-treated patients.
Conclusion: Treatment with ESK is associated with fewer weight-related TEAEs, less weight gain, fewer metabolic changes, and fewer weight-related treatment discontinuations compared to QXR treatment.
