Efficacy of esketamine nasal spray for treatment-resistant depression: A meta-analysis of randomized controlled studies.
Yannan Ouyang, Juan Li
Medicine February 28, 2025 DOI: 10.1097/MD.0000000000041495 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression |
| Intervention | Esketamine nasal spray |
| Topics | Depression Esketamine |
| Keywords | Mental health Medical research Antidepressants Breakthrough treatments |
| Citations | 8 |
| Key findings | Esketamine nasal spray is associated with significantly reduced MADRS scores, increased response rates, and improved functioning, but also increased dizziness and nausea. |
Abstract
The efficacy of esketamine nasal spray for treatment-resistant depression remains controversial. This systematic review and meta-analysis was conducted to explore the influence of esketamine nasal spray on treatment efficacy for treatment-resistant depression. We conducted a comprehensive search across multiple databases, including PubMed, EMbase, Web of Science, EBSCO, and Cochrane library through March 2024 for randomized controlled trials (RCTs) assessing the effect of esketamine nasal spray on the treatment efficacy of depression. This meta-analysis was performed using the random-effect model. Five RCTs are included in the meta-analysis. Overall, compared with control group treatment-resistant depression, esketamine nasal spray is associated with significantly reduced MADRS scores (SMD = -3.88; 95% confidence interval [CI] = -5.71 to -2.05; P < .0001), increased response rates (RR = 1.99; 95% CI = 1.28-3.10; P = .002), decreased Sheehan Disability Scale (SMD = -3.01; 95% CI = -4.39 to -1.64; P < .0001) and PHQ-9 scores (SMD = -2.32; 95% CI = -3.51 to -1.13; P = .0001), but leads to the increase in dizziness (RR = 3.55; 95% CI = 2.37-5.32; P < .00001) and nausea (RR = 3.88; 95% CI = 2.10-7.18; P < .0001). Esketamine nasal spray is beneficial to improve the efficacy of treatment-resistant depression.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression | 2020 | Systematic review and meta-analysis | n = 1,877 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |
Citations in the library
Cited by 8
- Ketamine pharmacotherapy for major depressive disorder: A narrative review Progress in Neuro-Psychopharmacology and Biological Psychiatry February 27, 2026
- Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis. Pharmaceuticals May 9, 2025
- Comparative Efficacy of Esketamine Nasal Spray Versus Quetiapine Extended Release as Adjunctive Treatments for Treatment-Resistant Depression: A Systematic Review Annals of Clinical Psychiatry July 29, 2026
- Esketamine for treatment-resistant depression: Comparing two maintenance schedules in an observational real-world study Research Square July 9, 2026
- Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis Frontiers in Psychiatry July 3, 2026
and 3 more in the library
Cites 7
- 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 Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- 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
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
and 2 more in the library