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)
Study at a glance
AI-extracted from the abstract| 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 Esketamine |
| Keywords | Post-hoc analysis Placebo Depression economics Clinical global impression Nasal spray Antidepressant Clinical trial Nasal administration Immunology |
| Citations | 19 |
| Registration | NCT02417064 NCT02418585 |
| Key findings | 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).
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Esketamine plus a new oral antidepressant increased odds of response and remission versus antidepressant plus placebo, but within the esketamine group response and remission were more likely in patients without significant anxiety at baseline.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for anxiety, most cited first.
Citations in the library
Cited by 15
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Personalized use of ketamine and esketamine for treatment-resistant depression. Translational Psychiatry November 29, 2024
- Esketamine Treatment Trajectory of Patients with Treatment-Resistant Depression in the Mid and Long-Term Run: Data from REAL-ESK Study Group. Current Neuropharmacology 2025
- At-home, telehealth-supported ketamine treatment for depression: Findings from longitudinal, machine learning and symptom network analysis of real-world data. Journal of Affective Disorders September 15, 2024
- Demographic and clinical predictors of response and remission in the treatment of major depressive disorder with ketamine and esketamine: A systematic review. Psychiatry Research March 1, 2025
and 10 more in the library
Cites 6
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder International Journal of Environmental Research and Public Health April 17, 2018
- Treatment Response With Esketamine Nasal Spray Plus an Oral Antidepressant in Patients With Treatment-Resistant Depression Without Evidence of Early Response The Journal of Clinical Psychiatry July 16, 2021
- The effect of esketamine in patients with treatment‐resistant depression with and without comorbid anxiety symptoms or disorder Depression and Anxiety July 22, 2021
and 1 more in the library