Esketamine in Treatment-Resistant Depression and Suicidal Ideation: A Systematic Review
Natalia Dudziak, Zuzanna Drozd, Bartosz Niemiec, Szymon Piosik, Bruno Olesiński, Łukasz Piasecki, Zuzanna Guzowicz, Monika Anna Kamińska, Patrycja Gągałka
Journal of Education Health and Sport November 29, 2025 DOI: 10.12775/jehs.2025.81.66740 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression or depression with active suicidal ideation |
| Intervention | Esketamine nasal spray |
| Dose | 84 mg |
| Topics | Depression Ketamine Esketamine |
| Keywords | Suicidal ideation Depression economics Placebo Adverse effect Depressive symptoms Anesthesia Citalopram Nausea Clinical trial Poison control |
| Key findings | Esketamine nasal spray rapidly reduces depressive symptoms and suicidal ideation, with effects within hours and sustained benefits, showing superior results versus placebo and comparators. |
Abstract
Background. Major depressive disorder affects 20% of the global population, with treatment-resistant depression in 10-30% of cases. Patients with acute suicidal ideation need immediate intervention, yet conventional antidepressants require weeks to work. Esketamine offers rapid symptom reduction through NMDA receptor antagonism. Aim. To systematically review current evidence on efficacy and safety of esketamine nasal spray in treating depression with active suicidal ideation and treatment-resistant depression, focusing on rapidity of response and clinical outcomes. Material and methods. PubMed search using terms "esketamine, depression, suicide" and related. After screening, 11 studies from 2020 onwards were analyzed. Results. ASPIRE II showed esketamine 84mg superior to placebo at 24 hours: MADRS reduction -15.7 vs -12.4 points (p=0.006), with effects at 4 hours. In 456 patients, response rates were 34.5% vs 25.3%, remission 20.4% vs 9.8% at 24 hours. Versus quetiapine, esketamine achieved 27.1% vs 17.6% remission at week 8 (p=0.003). Long-term data (1,148 patients, 31.5 months) showed suicide attempts 0.361 and deaths 0.036 per 100 patient-years. Common side effects: dizziness (38-47%), nausea (27-33%), transient dissociation; 4-11% discontinued treatment. Conclusions. Esketamine demonstrates rapid efficacy in reducing depressive symptoms and suicidal ideation, with effects within hours and sustained benefits. It shows superior results versus placebo and comparators with acceptable safety, making it valuable for acute suicidal ideation requiring rapid intervention.
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 |