The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis

The efficacy of ketamine in reducing suicidal ideation (SI) has been previously reported. We aimed to evaluate acute anti-SI effects of single-dose ketamine in different formulations/routes of administration by pooling results from randomized controlled trials (RCTs). A systematic search was conducted on Cochrane, Embase, Medline, and PubMed from inception to July 1st, 2020. Studies were selected based on pre-determined eligibility criteria. Effect sizes of different formulations/routes at various time points were computed using random-effects models. With data from nine eligible RCTs (n = 197), the pooled effect size for anti-SI effects at the 24-h time point was 1.035 (N = 6, CI: 0.793 to 1.277, p < 0.001) for intravenous (IV) racemic ketamine and 1.309 (N = 1, CI: 0.857 to 1.761, p < 0.001) for intranasal (IN) esketamine. An additional five RCTs were available for qualitative analysis. RCTs were identified for oral/sublingual ketamine for depression, however, none of these trials reported anti-SI effects preventing quantitative analysis for these routes of delivery. No RCTs for intramuscular (IM) ketamine were identified. The findings suggest that single-dose IV ketamine/IN esketamine is associated with robust reductions in suicidal thoughts at 2-h, 4-h, and 24-h post-intervention. In addition, future studies on IM/oral/sublingual ketamine and comparative studies are warranted to evaluate the anti-SI efficacy of distinct formulations and routes of administration.

Automated summary

The study aimed to evaluate the acute anti-suicidal ideation effects of single-dose ketamine in different formulations and routes of administration by pooling the results from randomized controlled trials. The findings suggest that intravenous ketamine and intranasal esketamine are associated with robust reductions in suicidal thoughts at 2-h, 4-h, and 24-h post-intervention. Further research on intramuscular, oral, and sublingual ketamine, as well as comparative studies, are needed to evaluate the efficacy of these formulations and routes of administration in reducing suicidal ideation.