Esketamine nasal spray versus quetiapine XR in adults with treatment-resistant depression: a secondary analysis of the ESCAPE-TRD randomized clinical trial.
Roger S McIntyre, Gregory W Mattingly, Yordan Godinov, Jozefine Buyze, Ibrahim Turkoz, Patricia Cabrera, Manish M Patel, Larry Martinez, Mai Himedan, Oliver Lopena
CNS Spectrums January 17, 2025 DOI: 10.1017/S1092852924002451 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Open-label Peer reviewed |
|---|---|
| Sample size | 636 |
| Population | Adults aged 18-64 with treatment-resistant depression |
| Interventions | Esketamine nasal spray Quetiapine extended-release |
| Duration | 32-week treatment period |
| Topics | Depression Esketamine |
| Keywords | Quetiapine Remission Treatment-resistant depression trd Refractory depression Antidepressants depression medication Depression drugs Esketamine spravato Ketamine derivative Drug comparison studies |
| Citations | 9 |
| Registration | NCT04338321 |
| Key findings | Esketamine nasal spray plus an oral antidepressant achieved higher remission rates and fewer discontinuations due to side effects than quetiapine extended-release plus an oral antidepressant over 32 weeks. |
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.