This robustness analysis of the ESCAPE-TRD Phase IIIb trial (n=676) investigates esketamine nasal spray versus quetiapine extended release for treatment-resistant depression (TRD). Esketamine significantly outperformed quetiapine in achieving remission at week 8 (MADRS ≤10) and maintaining relapse-free status through week 32, with hazard ratios favouring esketamine (HR: 1.658–1.711, p < 0.001).
Abstract of Efficacy of esketamine nasal spray over quetiapine extended release over the short and long term
“Background In patients with treatment resistant depression (TRD), the ESCAPE-TRD study showed esketamine nasal spray was superior to quetiapine extended release.
Aims To determine the robustness of the ESCAPE-TRD results and confirm the superiority of esketamine nasal spray over quetiapine extended release.
Method ESCAPE-TRD was a randomised, open-label, rater-blinded, active-controlled phase IIIb trial. Patients had TRD (i.e. non-response to two or more antidepressive treatments within a major depressive episode). Patients were randomised 1:1 to flexibly dosed esketamine nasal spray or quetiapine extended release, while continuing an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. The primary end-point was achieving a Montgomery–Åsberg Depression Rating Scale score of ≤10 at Week 8, while the key secondary end-point was remaining relapse free through Week 32 after achieving remission at Week 8. Sensitivity analyses were performed on these end-points by varying the definition of remission based on timepoint, threshold and scale.
Results Of 676 patients, 336 were randomised to esketamine nasal spray and 340 to quetiapine extended release. All sensitivity analyses on the primary and key secondary end-point favoured esketamine nasal spray over quetiapine extended release, with relative risks ranging from 1.462 to 1.737 and from 1.417 to 1.838, respectively (all p < 0.05). Treatment with esketamine nasal spray shortened time to first and confirmed remission (hazard ratio: 1.711 [95% confidence interval 1.402, 2.087], p < 0.001; 1.658 [1.337, 2.055], p < 0.001).
Conclusion Esketamine nasal spray consistently demonstrated significant superiority over quetiapine extended release using all pre-specified definitions for remission and relapse. Sensitivity analyses supported the conclusions of the primary ESCAPE-TRD analysis and demonstrated robustness of the results.”
Authors: Allan H. Young, Pierre-Michel Llorca, Andrea Fagiolini, Peter Falkai, Narcís Cardoner, René E. Nielsen, Ola Blomqvist, Yordan Godinov, Benoît Rive, Joris Diels, Siobhán Mulhern-Haughey & Andreas Reif
Summary of Efficacy of esketamine nasal spray over quetiapine extended release over the short and long term
Treatment-resistant depression (TRD) is a subtype of major depressive disorder (MDD) characterised by a lack of response to at least two prior antidepressant treatments administered at adequate doses and durations. It is estimated to affect 10–30% of individuals with MDD. The treatment goals for TRD include achieving remission—defined as a significant reduction in depressive symptoms—and preventing relapse over the long term. However, remission rates diminish as patients undergo successive treatments, highlighting the unmet need for effective TRD therapies.
Current options for managing TRD include quetiapine extended release, which is commonly used as an augmentation strategy, and esketamine nasal spray, which is the only treatment specifically approved for TRD in Europe. Esketamine has shown efficacy in reducing depressive symptoms when combined with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). The ESCAPE-TRD study was the first head-to-head comparison of these treatments, designed to evaluate their efficacy over short- and long-term periods.
Aims
Find this paper
https://doi.org/10.1192/bjp.2024.124
Open Access | Google Scholar | Backup | 🕊
Cite this paper (APA)
Young, A. H., Llorca, P.-M., Fagiolini, A., Falkai, P., Cardoner, N., Nielsen, R. E., Blomqvist, O., Godinov, Y., Rive, B., Diels, J., Mulhern-Haughey, S., & Reif, A. (2024). Efficacy of esketamine nasal spray over quetiapine extended release over the short and long term: sensitivity analyses of ESCAPE-TRD, a randomised phase IIIb clinical trial. The British Journal of Psychiatry
Study details
Compounds studied
Ketamine
Topics studied
Depression
Treatment-Resistant Depression
Study characteristics
Single-Blind
Open-Label
Randomized
Participants
676
Humans
Linked Research Papers
Notable research papers that build on or are influenced by this paper
Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant DepressionThis open-label Phase IIIb trial (n=676) compared the efficacy of esketamine nasal spray and extended-release quetiapine, combined with an SSRI or SNRI, in patients with treatment-resistant depression (TRD). The study found that a significantly higher percentage of patients in the esketamine group achieved remission at week 8 (27.1% vs 17.6%) and had no relapse through week 32 after remission at week 8 (21.7% vs 14.1%). Adverse events were consistent with the established safety profiles of the trial treatments.
Linked Clinical Trial
A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder (ESCAPE-TRD)This Phase III interventional trial (n=676) will evaluate the efficacy of flexibly dosed esketamine nasal spray compared with quetiapine extended-release (XR), both in combination with a continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI), in achieving remission in participants with treatment-resistant major depressive disorder (MDD) experiencing a moderate to severe depressive episode.