Efficacy of racemic ketamine or esketamine monotherapy for reducing suicidal ideation in uni- or bipolar depression: a systematic review and meta-analysis.

Racemic ketamine monotherapy rapidly reduces suicidal thoughts in people with unipolar or bipolar depression, but the effect is short-lived and esketamine shows inconsistent evidence. A meta-analysis of 13 randomized controlled trials involving 1,109 individuals found that those receiving racemic ketamine had a significantly higher rate of acute remission of suicidal ideation compared to placebo or midazolam (risk ratio 2.06). Racemic ketamine also lowered suicidal ideation scores. However, no significant long-term anti-suicidal effects were found for either racemic ketamine or esketamine, and evidence for esketamine was inconsistent.

Study at a glance

Abstract

The current systematic review and meta-analysis examined the effect of racemic ketamine or esketamine on suicidal ideation in individuals with uni- or bipolar depression. We searched the MEDLINE, Embase, Central, PsycINFO, and Web of Science databases to identify randomized controlled trials that examined the effect of racemic ketamine or esketamine monotherapy on suicidal ideation (SI) in individuals with uni- or bipolar depression. The two monotherapies were compared; the primary outcome was the rate of remission of SI, and the secondary outcome was the SI score. The risk ratio was used as an effect size measure for binary variables, while the standardized mean difference was used as an effect size measure for continuous variables. Our meta-analysis included 13 randomized controlled trials involving 1,1109 individuals with uni- or bipolar depression. Patients receiving racemic ketamine monotherapy had a significantly higher acute SI remission rate than those receiving placebo or midazolam (RR = 2.06, 95% CI 1.47 to 2.91, P < 0.0001). Racemic ketamine also led to significantly lower SI scores than placebo or midazolam (SMD = -0.36, 95% CI -0.71 to -0.01, P = 0.04). The evidence for the treatment of SI with esketamine was inconsistent. The pooled effect sizes for long-term anti-SI effects did not reveal significant differences between therapies. Our study indicated the efficacy of racemic ketamine monotherapy for rapidly and transiently reducing SI in individuals with uni- or bipolar depression, but the efficacy of racemic ketamine monotherapy against long-term suicidal ideation remains unclear. There is not -sufficient evidence to support the anti-suicidal effects of esketamine monotherapy.Protocol registration: Prospero registration number: CRD42023434380.