The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis
S. Wilkinson, Elizabeth D. Ballard, Michael H. Bloch, S. Mathew, James W. Murrough, Adriana Feder, Peter Šóš, Gang Wang, Carlos A. Zarate, Gerard Sanacora
American Journal of Psychiatry October 3, 2017 DOI: 10.1176/appi.ajp.2017.17040472 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and individual participant data meta-analysis Peer reviewed |
|---|---|
| Sample size | 167 |
| Population | Depressed patients with suicidal ideation at baseline |
| Intervention | Ketamine |
| Dose | single dose |
| Duration | Up to one week post-ketamine administration |
| Topics | Esketamine Ketamine |
| Citations | 680 |
| Key findings | Ketamine rapidly reduces suicidal ideation for up to one week, with effects partially independent of mood improvement. |
Abstract
Objective: Suicide is a public health crisis with limited treatment options. We 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 (using either saline or midazolam as control). The analysis included only participants with 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 (Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D)) and self-reported scales (Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) or Beck Depression Inventory (BDI)), obtained for up to one week post-ketamine administration.
Results: Ketamine rapidly reduced (one day) suicidal ideation on both the clinician-administered (p<0.001) and self-reported outcome measures (p<0.001). Effect sizes were moderate-to-large (Cohen’s d=0.51–0.85) at all time points post-dose. Sensitivity analysis demonstrated that, compared to controls, ketamine had significant benefits on the individual suicide items of the MADRS, HAM-D, and QIDS-SR (all p<0.001) but not on the BDI (p=0.080). 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 one day and for up to one week in depressed patients with suicidal ideation. Ketamine’s effects on suicidal ideation were partially independent of its effects on mood, though 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.
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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State of the evidence: Ketamine Supports
A single dose of ketamine rapidly reduced suicidal ideation on clinician-administered and self-reported measures for up to one week, with moderate-to-large effect sizes, partially independent of mood improvement.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes | 1999 | Systematic review |
Citations in the library
Cited by 283
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- 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
- Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Journal of Affective Disorders September 23, 2020
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Reviewing the Potential of Psychedelics for the Treatment of PTSD The International Journal of Neuropsychopharmacology March 12, 2020
and 278 more in the library
Cites 15
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders JAMA Psychiatry March 1, 2017
and 10 more in the library