Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray
Ibrahim Turkoz, J. Craig Nelson, Samuel T. Wilkinson, Stephane Borentain, Matthew Macaluso, Madhukar H. Trivedi, David Williamson, John J. Sheehan, Giacomo Salvadore, Jaskaran Singh, Ella Daly
Psychiatry Research March 15, 2023 DOI: 10.1016/j.psychres.2023.115165 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractA post hoc analysis of two pooled 4-week phase 3 trials examined predictors of response and remission in patients with treatment-resistant depression receiving esketamine nasal spray plus a new oral antidepressant compared to a new oral antidepressant plus placebo nasal spray. Younger age, being employed, having fewer failed antidepressants in the current episode, and early reduction in Clinical Global Impression-Severity score at day 8 predicted better outcomes. Those on esketamine had 68% higher odds of response and 55% higher odds of remission. In the esketamine group, response was more likely in employed patients, those without baseline anxiety, and those with early symptom improvement.
Study at a glance
| Characteristics | Post hoc analysis of two pooled phase 3 double-blind placebo- and active-controlled trials Peer reviewed |
|---|---|
| Sample size | 518 |
| Population | Patients with treatment-resistant depression |
| Interventions | Esketamine nasal spray newly initiated oral antidepressant placebo nasal spray |
| Duration | 4-week intervention |
| Topics | Anxiety Depression |
| Keywords | Post-hoc analysis Internal medicine Placebo Depression economics |
| Citations | 19 |
| Registration | NCT02417064 NCT02418585 |
| Key finding | Esketamine nasal spray plus a new oral antidepressant significantly increased odds of response and remission compared to a new oral antidepressant plus placebo nasal spray in treatment-resistant depression. |
Abstract
This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and psychiatric characteristics as potential predictors of response (≥50% reduction from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) and remission (MADRS total score ≤12) at day 28. Overall, younger age, any employment, fewer failed ADs in the current depressive episode, and reduction in Clinical Global Impression-Severity (CGI-S) score at day 8 were significant positive predictors of response and remission at day 28. Treatment assignment was an important predictor of both response and remission. Patients treated with ESK+AD had 68% and 55% increased odds of achieving response and remission, respectively, versus those treated with AD+PBO. In the ESK+AD group, attainment of response and remission was more likely in patients who were employed, without significant anxiety at baseline, and who experienced a reduction in CGI-S score at day 8. Identification of predictors of response and remission may facilitate identification of those patients with TRD most likely to benefit from ESK+AD. Trial Registration: ClinicalTrials.gov: NCT02417064 (clinicaltrials.gov/ct2/show/NCT02417064) and NCT02418585 (clinicaltrials.gov/ct2/show/NCT02418585).