Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2018 Feb 1;175(2):150-158.
doi: 10.1176/appi.ajp.2017.17040472. Epub 2017 Oct 3.

The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Samuel T Wilkinson  1 , Elizabeth D Ballard  1 , Michael H Bloch  1 , Sanjay J Mathew  1 , James W Murrough  1 , Adriana Feder  1 , Peter Sos  1 , Gang Wang  1 , Carlos A Zarate Jr  1 , Gerard Sanacora  1
Affiliations
Meta-Analysis

The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis

Samuel T Wilkinson et al. Am J Psychiatry. .

Abstract

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.

Keywords: Ketamine; Mood Disorders-Bipolar; Mood Disorders-Unipolar; Rapid-Acting Antidepressants; Suicide.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A flowchart depicting the procedure for selecting eligible trials from identified references.
Figure 2
Figure 2
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies) adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined clinician-reported, converted to Montgomery-Åsberg Depression Rating Scale (MADRS) units (N=167, k=8, chi-square=50.6, p<0.001 for overall time x treatment interaction), (B) MADRS item 10 (N=140, k=6, chi-square=35.0, p<0.001 for overall time x treatment interaction), and (C) Hamilton Depression Rating Scale (HAM-D) item 3 (N=89, k=4, chi-square=19.4; p<0.001 for overall time x treatment interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 2
Figure 2
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies) adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined clinician-reported, converted to Montgomery-Åsberg Depression Rating Scale (MADRS) units (N=167, k=8, chi-square=50.6, p<0.001 for overall time x treatment interaction), (B) MADRS item 10 (N=140, k=6, chi-square=35.0, p<0.001 for overall time x treatment interaction), and (C) Hamilton Depression Rating Scale (HAM-D) item 3 (N=89, k=4, chi-square=19.4; p<0.001 for overall time x treatment interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 2
Figure 2
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies) adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined clinician-reported, converted to Montgomery-Åsberg Depression Rating Scale (MADRS) units (N=167, k=8, chi-square=50.6, p<0.001 for overall time x treatment interaction), (B) MADRS item 10 (N=140, k=6, chi-square=35.0, p<0.001 for overall time x treatment interaction), and (C) Hamilton Depression Rating Scale (HAM-D) item 3 (N=89, k=4, chi-square=19.4; p<0.001 for overall time x treatment interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 3
Figure 3
Proportion of subjects without suicidal ideation at each time point post-dose using (A) clinician-reported outcome measures (Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D)) and (B) self-reported outcome measures (Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Beck Depressive Inventory (BDI)); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 3
Figure 3
Proportion of subjects without suicidal ideation at each time point post-dose using (A) clinician-reported outcome measures (Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D)) and (B) self-reported outcome measures (Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) or Beck Depressive Inventory (BDI)); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 4
Figure 4
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies), adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined self-reported scale scores (N=144, k=8, chi-square=45.5, p<0.001 for overall group x time interaction); (B) Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) item 12 (N=77, k=4, chi-square=32.5, p<0.001 for overall group x time interaction); and (C) Beck Depression Inventory (BDI) item 9 (N=67, k=4, chi-square=8.34, p=0.080 for overall group x time interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 4
Figure 4
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies), adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined self-reported scale scores (N=144, k=8, chi-square=45.5, p<0.001 for overall group x time interaction); (B) Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) item 12 (N=77, k=4, chi-square=32.5, p<0.001 for overall group x time interaction); and (C) Beck Depression Inventory (BDI) item 9 (N=67, k=4, chi-square=8.34, p=0.080 for overall group x time interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
Figure 4
Figure 4
Effect of a single dose of ketamine on suicidal ideation. Means from multilevel, mixed effects, general linear model (subjects nested within studies), adjusting for baseline suicidal ideation and between-study effects. Outcomes are: (A) combined self-reported scale scores (N=144, k=8, chi-square=45.5, p<0.001 for overall group x time interaction); (B) Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) item 12 (N=77, k=4, chi-square=32.5, p<0.001 for overall group x time interaction); and (C) Beck Depression Inventory (BDI) item 9 (N=67, k=4, chi-square=8.34, p=0.080 for overall group x time interaction); *p<0.05, **p<0.01, ***p<0.001. Error bars are 95% confidence intervals.
See this image and copyright information in PMC

Comment in

References

    1. Aleman A, Denys D. Mental health: A road map for suicide research and prevention. Nature. 2014;509(7501):421–3. - PubMed
    1. Griffiths JJ, Zarate CA, Jr, Rasimas JJ. Existing and novel biological therapeutics in suicide prevention. Am J Prev Med. 2014;47(3 Suppl 2):S195–203. - PMC - PubMed
    1. Curtin SC, Warner M, Hedegaard H. Increase in Suicide in the United States, 1999–2014. NCHS Data Brief. 2016;(241):1–8. - PubMed
    1. Cavanagh JT, Carson AJ, Sharpe M, Lawrie SM. Psychological autopsy studies of suicide: a systematic review. Psychol Med. 2003;33(3):395–405. - PubMed
    1. National Action Alliance for Suicide Prevention: Research Prioritization Task Force. A prioritized research agenda for suicide prevention: An action plan to save lives. Rockville, MD: National Institute of Mental Health and the Research Prioritization Task Force; 2014.

Publication types