Clinical trials since 2020 of rapid anti-suicidal ideation effects of ketamine and its enantiomers: a systematic review.
Sumra Sajid, J John Mann, Michael F Grunebaum
Translational Psychiatry February 6, 2025 DOI: 10.1038/s41398-025-03255-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Open-label Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Adults with clinically significant suicidal ideation |
| Interventions | ketamine S-ketamine R-ketamine |
| Topics | Esketamine Ketamine |
| Keywords | Mental-health Suicide-prevention Ketamine-therapy Psychiatric-treatment Antidepressants |
| Citations | 3 |
| Key findings | Multiple doses of intravenous ketamine or S-ketamine reduce suicidal ideation for days to weeks, while single doses and intranasal administration show less consistent effects. |
Abstract
Suicide is a global public health problem with few empirically supported treatments. We conducted a systematic review of clinical trials (CT) since 2020 of racemic ketamine or one of its enantiomers' (R/S) potential to reduce suicidal ideation or behavior (SIB). An initial PubMed search on April 15th, 2024 yielded 2483 results. 104 relevant CTs were identified. An additional search using other search engines on March 19th, 2024 yielded 52 sources. After screening, 14 RCTs met the inclusion criteria which required clinically significant SIB among participants, ketamine or one of its enantiomers as an anti-SIB treatment, and SIB as an outcome. We excluded neuroimaging studies, meta-analyses, reviews, and case reports. Open-label studies were also excluded except in the case of R-ketamine where we included 2 open trials due to limited published data for this enantiomer, yielding a total of 16 CTs. We used the Revised Cochrane risk-of-bias tool for the RCTs. CTs reviewed had suicidal ideation (SI) but none had suicidal behavior as an outcome. The studies include ketamine augmentation of other treatments such as electroconvulsive therapy (ECT), various routes of administration - intravenous (IV), intramuscular (IM), and intranasal (IN) - and single versus multiple dose designs. Multiple doses of IV ketamine/S-ketamine produced reductions in SI for periods of several days to weeks, while single doses showed shorter, more variable effects. Multiple and single doses of IN ketamine/S-ketamine and single doses of IV ketamine produced less consistent anti-SI results. IN and IV ketamine/S-ketamine administration appears to be well tolerated. R-ketamine appears to produce fewer side effects, but additional clinical research is needed to clarify its antidepressant and anti-SI effects in humans. This review affirms the time-limited, anti-SI effects of ketamine and the need for personalized treatment. Limitations include study heterogeneity, small samples, and paucity of data for suicidal behavior or R-ketamine.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 2
- New Agents in the Treatment of Psychiatric Disorders: What Innovations and in What Areas of Psychopathology? Pharmaceuticals April 30, 2025
- Clinical correlates of non-responders to ketamine in terms of self-assessed life engagement among treatment-resistant depression patients. Journal of Psychiatric Research September 10, 2026
Cites 42
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
and 37 more in the library