Efficacy of intravenous ketamine and intranasal esketamine with dose escalation for Major depression: A systematic review and meta-analysis.
Ashok Seshadri, Larry J Prokop, Balwinder Singh
Journal of affective disorders July 1, 2024 DOI: 10.1016/j.jad.2024.03.137 via PubMed
Summary
AI-generated from the abstractA systematic review and meta-analysis of 12 randomized controlled trials found that intravenous ketamine reduces depression symptoms in treatment-resistant depression at doses as low as 0.2 mg/kg, with increasing response at 0.5 mg/kg but no additional benefit at 1 mg/kg. Intranasal esketamine doses of 56–84 mg were more effective than 28 mg. Higher intravenous doses above 0.5 mg/kg did not lead to greater treatment response. The overall quality of evidence was low, limited by few studies, and publication bias was high.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 12 |
| Population | Adults with treatment-resistant depression |
| Intervention | Intranasal esketamine |
| Dose | 0.2-0.5 mg/kg and >0.5 mg/kg for IV ketamine; 56-84 mg and 28 mg for IN esketamine |
| Topics | Depression |
| Keywords | Clinical trials Dose escalation Intranasal esketamine Intravenous ketamine |
| Citations | 50 |
| Key finding | Intravenous ketamine shows efficacy at doses as low as 0.2 mg/kg with no added benefit above 0.5 mg/kg, while intranasal esketamine is most effective at 56–84 mg. |
Abstract
Intravenous (IV) racemic ketamine and intranasal (IN) esketamine have demonstrated rapid antidepressant effects in treatment-resistant depression (TRD). This systematic review aims to evaluate the efficacy and safety of ketamine and esketamine at various dosages for depression. We included randomized controlled trials (RCTs) with parallel group dose comparison of ketamine and esketamine for depression/TRD. Ovid Medline, Embase, PsycINFO, Scopus and Cochrane databases were searched. Standardized mean differences were calculated using Hedges'-g to complete random effects meta-analysis. The efficacy outcomes were changes in depression outcomes for IV ketamine and IN esketamine respectively. Safety was assessed by reported adverse effects. A random effects meta-analysis of studies (n = 12) showed efficacy in reducing depression symptoms with IV ketamine (Hedges'g = 1.52 [0.98-2.22], Z = 4.23, p 0.2-0.5 mg/kg and > 0.5 mg/kg. Higher IV ketamine doses (>0.5 mg/kg) did not lead to greater treatment response. Esketamine doses of 56-84 mg were superior to 28 mg dose. Overall quality of evidence was low and limited by small number of studies. Publication bias was high. This meta-analysis suggests that IV ketamine may be efficacious at doses as low as 0.2 mg/kg, with increasing dose response at 0.5 mg/kg, without demonstrable increased benefit at 1 mg/kg, based on a small number of studies. Efficacy for IN esketamine increases with doses above 28 mg with best response being found between 56 and 84 mg for reducing depressive symptoms.