The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis

Abstract Background Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes. Methods Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2–6 days, 7–20 days, 21–28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine. Results The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591–1.903, p  Limitations Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery. Conclusions The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.