Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire.
Jennifer Kern Sliwa, Ronaldo R Naranjo, Ibrahim Turkoz, Mary Pat Petrillo, Patricia Cabrera, Madhukar H. Trivedi
CNS Spectrums June 1, 2024 DOI: 10.1017/S1092852924000105 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pooled analysis of two randomized controlled trials and one relapse-prevention study Peer reviewed |
|---|---|
| Sample size | 565 |
| Population | Adults with treatment-resistant depression |
| Interventions | Esketamine nasal spray newly initiated oral antidepressant placebo nasal spray |
| Duration | 28 days for TRANSFORM-1/TRANSFORM-2; maintenance treatment period for SUSTAIN-1 |
| Topics | Depression Esketamine |
| Keywords | Oral antidepressant Severity Treatment resistant Mental health Depression treatment Breakthrough medicine Antidepressants Clinical research |
| Citations | 5 |
| Registration | NCT02417064 NCT02418585 NCT02493868 |
| Key findings | Esketamine nasal spray plus a newly initiated oral antidepressant significantly improved depressive symptoms and increased the proportion of patients achieving clinically meaningful improvement compared to oral antidepressant plus placebo spray. |
Abstract
To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD). Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models. In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (-12.8 [0.46] vs -10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044). In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS. ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.
Citations in the library
Cited by 3
- A Multi-Center, Open-Label, Single-Arm Study to Investigate the Early Effectiveness of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Using a Mobile Self-Monitoring Application. Pharmaceuticals August 30, 2024
- Efficacy and Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials medRxiv September 25, 2025
- Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes. Journal of Affective Disorders October 1, 2025
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 of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 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
- Meaningful Change in Depression Symptoms Assessed with the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) Among Patients with Treatment Resistant Depression in Two, Randomized, Double-blind, Active-controlled Trials of Esketamine Nasal Spray Combined With a New Oral Antidepressant Journal of Affective Disorders November 14, 2020
- 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
and 1 more in the library