Acute Effects of Intravenous Sub-Anesthetic Doses of Ketamine and Intranasal Inhaled Esketamine on Suicidal Ideation: A Systematic Review and Meta-Analysis.
Cheng-Chuan Chen, Na Zhou, Na Hu, Jian-Guo Feng, Xiao-Bin Wang
Neuropsychiatric Disease and Treatment March 14, 2023 DOI: 10.2147/ndt.s401032 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Meta-analysis Randomized Peer reviewed |
|---|---|
| Population | Depressed patients at risk for suicide, drawn from parallel randomized controlled trials |
| Interventions | Ketamine Esketamine |
| Dose | sub-anesthetic doses of intravenous ketamine; intranasal inhaled esketamine |
| Duration | Assessments at 4-6 hours and 24 hours after administration |
| Measures | Scale for Suicidal Ideation (SSI), Beck Scale for Suicide Ideation (BSS), Beck Depression Inventory (BDI), Modified Scale for Suicidal Ideation (MSSI) |
| Topics | Depression Esketamine Ketamine |
| Keywords | Suicide ideation |
| Key findings | Intravenous sub-anesthetic ketamine and intranasal esketamine both reduced suicidal ideation within 4 hours, with effects lasting 24 hours. Ketamine's effect was large at 4-6 hours (Cohen's d = 1.16) and medium-to-large at 24 hours (Cohen's d = 0.95), while esketamine's effect was small-to-medium at both 4-6 hours (Cohen's d = 0.26) and 24 hours (Cohen's d = 0.30). |
Abstract
Purpose: Suicide is a major public health concern with currently no validated and efficacious treatments approved. Preliminary evidence suggests that intravenous ketamine has rapid and sustained antidepressant effects, making it a candidate with therapeutic potential for depressed patients at risk for suicide. We conducted a meta-analysis to evaluate the efficacy of ketamine and esketamine in reducing suicidal ideation (SI), as well as their respective onset and duration of action. Data sources: We searched PubMed, Embase, Ovid, Cochrane, and Web of Science databases for studies published from inception to September 29, 2022. Study eligibility criteria: We conducted a systematic review of all parallel randomized controlled trials (RCTs) examining the effect and duration of ketamine or esketamine on SI. Our primary outcome measure was the Suicide Scale score, which was measured using the Scale for Suicidal Ideation (SSI), Beck Scale for Suicide Ideation (BSS), Beck Depression Inventory (BDI), or Modified Scale for Suicidal Ideation (MSSI). To obtain effect sizes (Cohen's d), we calculated the difference in Suicide Scale scores before and after administration in each group.
Results: Our study showed that intravenous sub-anesthetic doses of ketamine and intranasal inhaled esketamine had a significant anti-SI effect. Specifically, ketamine produced a large degree of anti-SI effect within the 4-6 hours (Cohen's d = 1.16, 95% CI: 0.50, 1.81) and a medium-large degree in the 24 hours (Cohen's d = 0.95, 95% CI: 0.48, 1.41). Esketamine, on the other hand, produced a small-medium degree of anti-SI effect within the 4-6 hours timeframe (Cohen's d = 0.26, 95% CI: 0.09, 0.44) and the 24 hours (Cohen's d = 0.30, 95% CI: 0.17, 0.47).
Conclusion: Intravenous sub-anesthetic doses of ketamine and intranasal inhaled esketamine could reduce SI within 4 hours and last for 24 hours.
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 17
- Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. American Journal of Psychiatry March 1, 2025
- Patient Experience with Intranasal Esketamine in Treatment-Resistant Depression: Insights from a Multicentric Italian Study (REAL-ESKperience) Journal of Personalized Medicine April 1, 2025
- Comparing the adverse effects of ketamine and esketamine between genders using FAERS data. Frontiers in Pharmacology 2024
- Anti-Suicidal Effects of Lithium, Ketamine, and Clozapine-A 10-Year Systematic Review. Pharmaceuticals May 18, 2025
- Efficacy of single and repeated ketamine administration for suicidal ideation in adults with psychiatric disorders: A meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 10, 2025
and 12 more in the library
Cites 26
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- 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
and 21 more in the library