Trajectory of response to esketamine nasal spray for treatment resistant depression: Findings from ESCAPE-TRD.

BACKGROUND

Previous research has demonstrated the positive impact of early remission on disease trajectory for patients with major depressive disorder. However, there is a paucity of literature assessing the response trajectory for patients with treatment resistant depression (TRD). These analyses investigated patient outcome trajectories to Week 32, including the relationship between short- and long-term outcomes with esketamine nasal spray (ESK-NS) treatment and symptom resolution.

METHODS

ESCAPE-TRD (NCT04338321), a randomized, open-label, phase IIIb study, evaluated the efficacy and safety of ESK-NS versus quetiapine extended release (QTP-XR) in patients with TRD. Rater-blinded Montgomery-Åsberg Depression Rating Scale (MADRS) total score was used to assess depressive symptoms and the trajectory of patient responses to Week 32. For ESK-NS versus QTP-XR, time to symptom resolution across MADRS items was evaluated using Kaplan-Meier analyses.

RESULTS

Of 676 patients, 336 and 340 were randomized to ESK-NS and QTP-XR, respectively. Most ESK-NS-treated patients achieved continuously improved outcomes to Week 32; early response was associated with better long-term outcomes. Among patients who achieved Week 4 response, 89.6% achieved remission at any point from Week 4 to 32; 78.3% of Week 8 responders achieved remission at any point from Week 8 to 32. Greater and earlier symptom resolution was observed with ESK-NS versus QTP-XR across most MADRS items.

CONCLUSIONS

Most ESK-NS-treated patients with TRD showed continuous improvements over time, with short-term response associated with better long-term outcomes. Long-term improvements were observed even among partial/minimal early responders, reinforcing the value of longer treatment. ESK-NS had a positive impact across the full spectrum of MADRS-assessed symptoms.