The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
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OBJECTIVE: Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. METHOD: Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167). A one-stage, individual participant data, meta-analytic procedure was employed using a mixed-effects, multilevel, general linear model. The primary outcome measures were the suicide items from clinician-administered (the Montgomery-Åsberg Depression Rating Scale [MADRS] or the Hamilton Depression Rating Scale [HAM-D]) and self-report scales (the Quick Inventory of Depressive Symptomatology-Self Report [QIDS-SR] or the Beck Depression Inventory [BDI]), obtained for up to 1 week after ketamine administration. RESULTS: Ketamine rapidly (within 1 day) reduced suicidal ideation significantly on both the clinician-administered and self-report outcome measures. Effect sizes were moderate to large (Cohen's d=0.48-0.85) at all time points after dosing. A sensitivity analysis demonstrated that compared with control treatments, ketamine had significant benefits on the individual suicide items of the MADRS, the HAM-D, and the QIDS-SR but not the BDI. Ketamine's effect on suicidal ideation remained significant after adjusting for concurrent changes in severity of depressive symptoms. CONCLUSIONS: Ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation. Ketamine's effects on suicidal ideation were partially independent of its effects on mood, although subsequent trials in transdiagnostic samples are required to confirm that ketamine exerts a specific effect on suicidal ideation. Additional research on ketamine's long-term safety and its efficacy in reducing suicide risk is needed before clinical implementation.
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Multiple meta-analyses and systematic reviews have shown that ketamine significantly reduces suicidal ideation from one day up to six weeks, and this effect appears at least partly independent of its mood effects.
“Multiple meta-analyses and systematic reviews have demonstrated that ketamine significantly reduces suicidal ideation within one day and up to six weeks, an effect that appears to be at least partially independent of its effects on mood [72][73][74][75].”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [72]
The Abstract Conclusions report reduced suicidal thoughts within one day and for up to one week, with effects partially independent of mood effects. They do not support the claimed duration of up to six weeks; the Discussion says effects beyond one week had not been thoroughly investigated. Page numbers are not provided in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPharmacological approaches, particularly rapid-acting agents (i.e., ketamine), have attracted growing attention due to their capacity to produce short-term reductions in depressive symptoms, suicidal ideation, and affective distress.
“Pharmacological approaches, particularly rapid-acting agents (i.e., ketamine), have attracted growing attention due to their capacity to produce short-term reductions in depressive symptoms, suicidal ideation, and affective distress [75,76,77].”
From Targeting Psychological Pain After a Suicide Attempt: Scoping Review and Intervention Protocol (2026) · cites this paper as [75]
The Introduction (page not provided) describes ketamine’s rapid antidepressant properties and the interest in its potential anti-suicidal effects. The Discussion’s Conclusions (page not provided) report reduced suicidal thinking within 24 hours, with benefits lasting up to one week. Our copy does not establish a separate short-term reduction in affective distress, so that part of the cited sentence is unsupported by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredKetamine is associated with rapid reductions in suicidal thoughts within hours.
“One example is ketamine, a glutamatergic modulator that has been associated with rapid reductions in suicidal thoughts within hours (11).”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [11]
Subsequent randomized controlled trials replicated a 60-70% response rate of ketamine in treatment-resistant depression populations.
“Subsequent randomized controlled trials (RCTs) replicated this finding, demonstrating a 60–70% response rate of ketamine in TRD populations.10–14”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [14]
Ketamine has been reported to have anti-suicidal and anti-anhedonic actions.
“Furthermore, ketamine has been reported to also have anti-suicidal and anti-anhedonic actions.14,19,20”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [14]
Ketamine's antidepressant properties are transient, lasting an average of 1 week following a single infusion and 18-19 days following repeated infusions.
“However, ketamine’s antidepressant properties are also transient, lasting an average of 1 week following a single infusion10–14 and 18–19 days following repeated infusions.15,16”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [14]
Multiple preclinical and clinical studies suggest that ketamine's anti-suicidal effects are at least partially disparate from its antidepressant action.
“Of note, multiple preclinical and clinical studies suggest that ketamine’s anti-suicidal effects are at least partially disparate from its AD action [98].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [98]
Many ketamine studies are hindered by homogenous samples, short durations, and limited real-world feasibility.
“Additionally, many studies are hindered by homogenous samples, short durations, and limited real-world feasibility [98,100].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [98]
Ketamine's antidepressant effects versus placebo are supported by several meta-analyses.
“Ketamine's antidepressant effects compared to placebo controls are further supported by several thorough meta-analyses [134-136].”
From Plasticity of synapses and reward circuit function in the genesis and treatment of depression (2023) · cites this paper as [135]
Results in individuals not fulfilling criteria for a full major depressive episode support the observation that ketamine is efficient independently from depressive episodes.
“Results in individuals not fulfilling the criteria for a full major depressive episode (whether bipolar or major depressive disorders) also support the observation that ketamine is efficient independently from depressive episodes, as suggested by previous authors.29”
From Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial (2022) · cites this paper as [29]
A meta-analysis of 10 trials analysing 157 suicidal patients found overall remission rates (clinician rated measures) of around 30% in the control group.
“This placebo effect is also higher than that found in a meta-analysis of 10 trials analysing 157 suicidal patients with overall remission rates (clinician rated measures) of around 30% in the control group.29”
From Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial (2022) · cites this paper as [29]
The effect of ketamine (42%) was lower than in the two other groups in our study (84% and 62%) and in the meta-analysis (around 55%).
“Moreover, the effect of ketamine (42%) was lower than in the two other groups in our study (84% and 62%) and in the meta-analysis (around 55%).29”
From Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial (2022) · cites this paper as [29]
Intravenous racemic ketamine has rapid antidepressant and anti-suicidal ideation effects.
“Intravenous racemic ketamine, a glutamatergic modulator with rapid antidepressant and anti-suicidal ideation effects, has emerged in the past decade as a potential intervention for individuals at risk for suicide (Wilkinson et al., 2018).”
From Clinical indicators of the suicide crisis and response to ketamine (2025) · cites this paper as Wilkinson et al., 2018
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- Authors
- Wilkinson, S. T., Ballard, E. D., Bloch, M. H., Mathew, S. J., Murrough, J. W., Feder, A., Sos, P., Wang, G., Zarate, C. A., & Sanacora, G.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- From the Department of Psychiatry and the Child Study Center, Yale School of Medicine, New Haven, Conn.; the Experimental Therapeutics and Pathophysiology Branch, NIMH, Bethesda, Md.; the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Michael E. Debakey VA Medical Center, Houston; the Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York; the Department of Psychiatry, First Faculty of Medicine, Charles University,...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2018-02-01
- Volume
- 175
- Issue
- 2
- Pages
- 150-158
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5794524
- OpenAlex
- W2762798648
- Cited by
- 696
- References
- 37
- Citations by year
- 2026: 63 · 2025: 65 · 2024: 79 · 2023: 81 · 2022: 94 · 2021: 93 · 2020: 107 · 2019: 70 · 2018: 43 · 2017: 1
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK6 RX002458)
- National Institutes of Health (UL1TR001863)
- National Institute of Mental Health (T32MH062994, Z01MH002857, L30 MH111000, ZIAMH002857, R25MH077823)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- ketamine, suicidal ideation, suicide risk, depression, rapid-acting antidepressants, single-dose intravenous administration, depressive symptoms, suicide prevention
- MeSH terms
- Adult, Depression, Major Depressive Disorder, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Linear Models, Treatment Outcome, Excitatory Amino Acid Antagonists, Multilevel Analysis, Self Report, Suicidal Ideation
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