Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses
T. Lima, M. B. Visacri, P. M. Aguiar
European Journal of Clinical Pharmacology October 27, 2021 DOI: 10.1007/s00228-021-03216-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with meta-analysis Randomized Peer reviewed |
|---|---|
| Population | Adult patients with depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Citations | 38 |
| Key findings | Ketamine and esketamine show significant antidepressant action within hours to days, but long-term efficacy and safety are lacking, and the methodological quality of the reviews is usually critically low. |
Abstract
To summarize the evidence of efficacy and safety of the use of ketamine and esketamine for depression. A literature search was performed in Medline, the Cochrane Library, LILACS, and CRD until November 2020. We included systematic reviews with meta-analyses of randomized controlled trials on the use of ketamine and esketamine in adult patients with depression. Two authors independently performed the study selection and data extraction. The AMSTAR-2 tool was used to appraise the quality of included reviews. A total of 118 records were identified, and 11 studies fully met the eligibility criteria. Compared to control, ketamine improved the clinical response at 40 min to 1 week and clinical remission at 80 min to 72 h, and esketamine improved both outcomes at 2 h to 4 weeks. Ketamine and esketamine also had a beneficial effect on the depression scales score and suicidality. For adverse events, oral ketamine did not show significant change compared to control, while intranasal esketamine showed difference for any events, such as dissociation, dizziness, hypoesthesia, and vertigo. Most reviews were classified as “critically low quality,” and none of them declared the source of funding of the primary studies and assessed the potential impact of risk of bias in primary studies. Ketamine and esketamine showed a significant antidepressant action within a few hours or days after administration; however, the long-term efficacy and safety are lacking. In addition, the methodological quality of the reviews was usually critically low, which may indicate the need for higher quality evidence in relation to the theme.
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 21
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Ketamine, an Old–New Drug: Uses and Abuses Pharmaceuticals December 21, 2023
- Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis Frontiers in Psychiatry February 1, 2024
- Drugs with glutamate-based mechanisms of action in psychiatry. Pharmacological Reports December 1, 2024
- Ketamine for suicidality: An umbrella review British Journal of Clinical Pharmacology April 22, 2022
and 16 more in the library
Cites 27
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- 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
and 22 more in the library