Esketamine nasal spray versus quetiapine XR in adults with treatment-resistant depression: a secondary analysis of the ESCAPE-TRD randomized clinical trial.

In adults with treatment-resistant depression, esketamine nasal spray combined with an oral antidepressant leads to higher remission rates than quetiapine extended-release combined with an oral antidepressant. Starting at week 8, 28.3% of esketamine-treated patients achieved remission compared to 18.6% on quetiapine, and by week 32, 55.7% versus 36.3%. Depressive symptoms improved more with esketamine from day 8 onward. Fewer patients stopped treatment due to side effects with esketamine (4.5%) than with quetiapine (10.1%). These results come from a secondary analysis of a randomized trial.

Study at a glance

Abstract

Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and quetiapine extended-release (XR) in patients with TRD treated in accordance with US prescribing information (USPI). ESCAPE-TRD (NCT04338321) was a randomized, open-label, rater-blinded phase 3b trial investigating ESK versus quetiapine XR for acute and maintenance treatment of patients with TRD. This secondary analysis included patients aged 18-64 years who were treated/dosed according to USPI. The primary endpoint was remission, defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 10. Treatment-emergent adverse events (TEAEs) leading to discontinuation were summarized descriptively. Among 636 patients in this secondary analysis (ESK, n = 316; quetiapine XR, n = 320), significantly more ESK-treated patients achieved remission starting at week 8 (28.3% versus 18.6%; P = 0.005) through week 32 (55.7% versus 36.3%; P < 0.001), compared with quetiapine XR-treated patients. There were clinically and statistically significant improvements in MADRS scores with ESK versus quetiapine XR at each visit from day 8 onwards. Fewer patients discontinued treatment because of TEAEs with ESK (4.5%) versus quetiapine XR (10.1%). Consistent with the primary analysis, this secondary analysis demonstrated that ESK improves short- and long-term outcomes compared with quetiapine XR in patients with TRD treated according to USPI.