Intranasal esketamine for patients with major depressive disorder: A systematic review and meta-analysis.
Soroush Oraee, Mohammadreza Alinejadfard, Hossein Golsorkh, Majid Sadeghian, Maryam Fanaei, Rosella Centis, Lia D'Ambrosio, Giovanni Sotgiu, Hossein Goudarzi, Giovanni Battista Migliori, Mohammad Javad Nasiri
Journal of Psychiatric Research December 1, 2024 DOI: 10.1016/j.jpsychires.2024.11.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Meta-analysis Peer reviewed |
|---|---|
| Sample size | 1,752 |
| Population | Individuals with Major Depressive Disorder and Treatment-Resistant Depression |
| Intervention | Intranasal esketamine |
| Dose | 28 to 84 mg |
| Topics | Depression Esketamine |
| Keywords | Intranasal esketamine Depression treatment Antidepressant therapy Esketamine breakthrough Mental health research |
| Citations | 13 |
| Key findings | Intranasal esketamine combined with an oral antidepressant significantly increases remission and response rates compared to placebo in patients with major depressive disorder and treatment-resistant depression. |
Abstract
A large number of people worldwide grapple with Major Depressive Disorder (MDD), and a significant portion of them confront resistance to conventional antidepressant treatments. Esketamine, an innovative intervention, has garnered attention due to its rapid-acting antidepressant effects. This meta-analysis aimed to evaluate the efficacy and safety of esketamine in individuals with MDD and Treatment-Resistant Depression (TRD). We performed an extensive search of electronic databases, including PubMed, EMBASE, and Cochrane Library, covering the period from inception to January 15, 2024, to identify clinical trials investigating the efficacy, safety, and tolerability of esketamine in individuals with MDD and TRD. Meta-analyses were conducted using a random-effect model, with the risk ratio (RR) chosen as the effect size. After screening, nine studies met inclusion criteria comprising 1752 patients. Esketamine dosages varied from 28 to 84 mg, administered intranasally in conjunction with an oral antidepressant. Intranasal esketamine exhibited significantly higher remission rates compared to the placebo (RR = 1.371, 95% CI: 1.194 to 1.574, p < 0.0001). Subgroup analysis revealed that the 84 mg and flexible doses were particularly effective. Moreover, intranasal esketamine demonstrated higher response rates compared to the placebo (RR = 1.274, 95% CI: 1.108 to 1.465, p-value = 0.001). Although adverse events were common in the esketamine group, they were generally tolerable. Intranasal esketamine demonstrated effectiveness in reducing scores among patients with MDD and TRD. The drug exhibited both safety and tolerability. However, further research is warranted to investigate its long-term effects and efficacy in specific patient subgroups.
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 10
- Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review. Medicina (Kaunas, Lithuania) March 21, 2025
- Ketamine pharmacotherapy for major depressive disorder: A narrative review Progress in Neuro-Psychopharmacology and Biological Psychiatry February 27, 2026
- EEG vigilance and response to oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized validation study. Psychiatry Research Neuroimaging July 1, 2025
- Interdisciplinary, Delphi-driven consensus guidelines on the use of intravenous ketamine infusions for depressive disorders from the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP3). Journal of Affective Disorders May 16, 2026
- Appetite measures as correlates of clinical response in mood disorders treated with ketamine: systematic review Frontiers in Nutrition August 21, 2025
and 5 more in the library
Cites 16
- 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 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
- Taming the Ketamine Tiger Anesthesiology August 6, 2010
- Management of Treatment-Resistant Depression: Challenges and Strategies Neuropsychiatric Disease and Treatment 2020
and 11 more in the library