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.
Jiaqi Xiong, Orly Lipsitz, David C J Chen-Li, Joshua D. Rosenblat, Nelson B Rodrigues, Isabelle P. Carvalho, Leanna M.W. Lui, Hartej Gill, Flora Narsi, Rodrigo B. Mansur, Yena Lee, Roger S McIntyre
Journal of Psychiatric Research December 11, 2020 DOI: 10.1016/j.jpsychires.2020.12.038 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Qualitative Peer reviewed |
|---|---|
| Sample size | 197 |
| Population | Participants in randomized controlled trials of ketamine for suicidal ideation |
| Intervention | Intranasal esketamine |
| Dose | single-dose |
| Topics | Depression Esketamine Ketamine |
| Citations | 122 |
| Key findings | Single-dose intravenous ketamine and intranasal esketamine are associated with robust reductions in suicidal thoughts at 2, 4, and 24 hours after administration. |
Abstract
The efficacy of ketamine in reducing suicidal ideation (SI) has been previously reported. We aimed to evaluate acute anti-SI effects of single-dose ketamine in different formulations/routes of administration by pooling results from randomized controlled trials (RCTs). A systematic search was conducted on Cochrane, Embase, Medline, and PubMed from inception to July 1st, 2020. Studies were selected based on pre-determined eligibility criteria. Effect sizes of different formulations/routes at various time points were computed using random-effects models. With data from nine eligible RCTs (n = 197), the pooled effect size for anti-SI effects at the 24-h time point was 1.035 (N = 6, CI: 0.793 to 1.277, p < 0.001) for intravenous (IV) racemic ketamine and 1.309 (N = 1, CI: 0.857 to 1.761, p < 0.001) for intranasal (IN) esketamine. An additional five RCTs were available for qualitative analysis. RCTs were identified for oral/sublingual ketamine for depression, however, none of these trials reported anti-SI effects preventing quantitative analysis for these routes of delivery. No RCTs for intramuscular (IM) ketamine were identified. The findings suggest that single-dose IV ketamine/IN esketamine is associated with robust reductions in suicidal thoughts at 2-h, 4-h, and 24-h post-intervention. In addition, future studies on IM/oral/sublingual ketamine and comparative studies are warranted to evaluate the anti-SI efficacy of distinct formulations and routes of administration.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Single-dose intravenous ketamine and intranasal esketamine were associated with reductions in suicidal thoughts at 2, 4, and 24 hours.
Synthesized
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 |
| 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 |
| Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis. Adults with treatment-resistant depression | 2024 | Systematic review and meta-analysis | n = 12 |