Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials

Abstract

Ketamine may reduce suicidal ideation in treatment-resistant depression. But it is not known how quickly this occurs and how long it persists. We undertook a systematic review and meta-analysis to determine the short and longer-term effectiveness of ketamine for suicidality. Method: CENTRAL, EMBASE, Medline, and PsycINFO were searched until 12 December, 2018. Randomised controlled trials of ketamine or esketamine reporting data on suicidal ideation, self-harm, attempted or completed suicide in adults diagnosed with any psychiatric disorder were included. Two reviewers independently extracted data and certainty of evidence was assessed using GRADE. Standardised mean difference (SMD) was used for continuous outcomes. Results: Twenty-five reports from 15 independent trials, with a total of 572 participants diagnosed with predominately affective disorders, were included. The evidence was rated moderate to low. In most trials ketamine was administered at 0·5mg/kg via a single intravenous infusion over a 30-45 minute period. Only a single trial of intransal esketamine was identified. At 4 hours post-infusion, treatment with ketamine was associated with a significant reduction in suicidal ideation scores (SMD -0·51, 95% CI -1·00 to -0·03), which persisted until 72 hours post-infusion (time-points between 12 and 24 hours: SMD -0·63, 95% CI -0·99 to -0·26; between 24 and 72 hours: -0·57, -0·99 to -0·14), but not thereafter. However, there was marked heterogeneity of results. In a single trial of esketamine, marginal effects on suicidal ideation were observed. In terms of actual suicidal behaviour there were virtually no data on effects of ketamine or esketamine. Conclusion: A single infusion of ketamine may have a short-term (up to 72 hours) beneficial impact on suicidal thoughts. While confirmation of these results in further trials is needed, they suggest possible use of ketamine to treat acute suicidality. Means of sustaining any anti-suicidal effect need to be found.