Effects of ketamine and esketamine on death, suicidal behaviour, and suicidal ideation in psychiatric disorders: A systematic review and meta-analysis
Martin Plöderl, Ruth Cooper, Tom Walker, Vibha Shah, Mark Horowitz, Constantin Volkmann, Joanna Moncrieff
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Background
Ketamine and esketamine have been claimed to possess anti-suicidal effects and potentially to transform suicide prevention. This study provides an updated overview of evidence from clinical trials.
Methods
We conducted a systematic review and meta-analysis to establish whether ketamine or esketamine reduce death, suicides, suicide attempts or suicidal ideation, compared to active or inert placebo among people with psychiatric disorders.
We searched EMBASE, PubMed and PsycINFO until 09.01.25 for randomised controlled trials which compared the effect of ketamine or esketamine with placebo for the treatment of psychiatric disorders. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Data were synthesised with meta-analysis, including methods for double-zero events.
Results
We included 66 trials with a total of 5103 participants. Rates of suicidal behavior were 0.91% for ketamine/esketamine and 1.23% for placebo, with the 95% confidence/credible intervals including the null-effect, OR = 0.86 [0.46 to 1.54] (Bayesian Analysis) and with low heterogeneity.
There were 21 (0.77%) suicide attempts, 4 (0.14%) suicides and 6 (0.21%) deaths with ketamine/esketamine compared to 26 (1.18%), 1 (0.05%) and 2 (0.09%) on placebo.
Ketamine/esketamine significantly reduced suicide ideation up to 2 weeks (standardized mean differences [SMD] at 12h to 24h of -0.35 [-0.51 to -0.19], I2 = 12%), but had small effects (SMD < 0.20, I2 ≤ 25%) thereafter.
Quality assessment revealed unreliable blinding and selective reporting.
Discussion
There is insufficient evidence for a preventive effect of ketamine/esketamine for suicidal behavior. The observed immediate but short-term effect on suicide ideation may be overestimated due to unblinding bias. Our review is the most comprehensive on suicidality, however, more evidence is needed to draw conclusions on suicidal behavior.
Other
No specific funding was involved. The protocol was registered with PROSPERO (CRD42023364156).
Web | PDF | Preprint: MedRxiv | Open Access
Martin Plöderl, Ruth Cooper, Tom Walker, Vibha Shah, Mark Horowitz, Constantin Volkmann, Joanna Moncrieff
[Line breaks added]
Background
Ketamine and esketamine have been claimed to possess anti-suicidal effects and potentially to transform suicide prevention. This study provides an updated overview of evidence from clinical trials.
Methods
We conducted a systematic review and meta-analysis to establish whether ketamine or esketamine reduce death, suicides, suicide attempts or suicidal ideation, compared to active or inert placebo among people with psychiatric disorders.
We searched EMBASE, PubMed and PsycINFO until 09.01.25 for randomised controlled trials which compared the effect of ketamine or esketamine with placebo for the treatment of psychiatric disorders. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Data were synthesised with meta-analysis, including methods for double-zero events.
Results
We included 66 trials with a total of 5103 participants. Rates of suicidal behavior were 0.91% for ketamine/esketamine and 1.23% for placebo, with the 95% confidence/credible intervals including the null-effect, OR = 0.86 [0.46 to 1.54] (Bayesian Analysis) and with low heterogeneity.
There were 21 (0.77%) suicide attempts, 4 (0.14%) suicides and 6 (0.21%) deaths with ketamine/esketamine compared to 26 (1.18%), 1 (0.05%) and 2 (0.09%) on placebo.
Ketamine/esketamine significantly reduced suicide ideation up to 2 weeks (standardized mean differences [SMD] at 12h to 24h of -0.35 [-0.51 to -0.19], I2 = 12%), but had small effects (SMD < 0.20, I2 ≤ 25%) thereafter.
Quality assessment revealed unreliable blinding and selective reporting.
Discussion
There is insufficient evidence for a preventive effect of ketamine/esketamine for suicidal behavior. The observed immediate but short-term effect on suicide ideation may be overestimated due to unblinding bias. Our review is the most comprehensive on suicidality, however, more evidence is needed to draw conclusions on suicidal behavior.
Other
No specific funding was involved. The protocol was registered with PROSPERO (CRD42023364156).
Web | PDF | Preprint: MedRxiv | Open Access
