Objective: Identify patient and disease characteristics associated with greater likelihood of achieving response and remission with esketamine nasal spray (ESK) plus a newly initiated oral antidepressant (AD) in patients with treatment-resistant depression (TRD).
Methods: Data for this post hoc analysis come from two 4-week, randomized, active-controlled studies (NCT02417064, NCT02418585) of ESK+AD versus an AD plus placebo nasal spray (PBO) in patients with TRD. Regression-based models identified baseline variables associated with response (50% improvement from baseline on MADRS) and remission (MADRS total score ≤12) at endpoint, in addition to Day 8 clinical symptom change scores.
Results: Significant predictors of response were treatment (ESK+AD versus AD+PBO), Day 8 change in CGI-S, employment status, baseline MADRS score, and C-SSRS score. ESK+AD was associated with 1.8x the odds of response at Day 28 versus AD+PBO. A 1-point reduction in CGI-S at Day 8 was associated with an 85% increase in the odds of achieving response at endpoint. Significant predictors of remission were treatment, Day 8 change in CGI-S, employment status, age, baseline PHQ-9 total score, and C-SSRS score. Patients receiving ESK+AD have approximately 1.5x the odds of remission at Day 28 compared with patients receiving AD+PBO. A 1-point reduction in Day 8 CGI-S was associated with 108% increase in the odds of achieving remission at Day 28.
Conclusion: Patients receiving ESK+AD were more likely to achieve response and remission at Day 28 than those receiving AD+PBO. Patients with early evidence of improvement in disease symptoms are more likely to achieve response and remission.