Does route of administration affect antidepressant efficacy of ketamine? A meta-analysis of double-blind randomized controlled trials comparing intravenous and intranasal administration. (December 2022) - Meiering, Marvin S.
Abstract: Intranasal (IN) and intravenous (IV) applications of ketamine have been proven effective for the treatment of depression, but direct comparative trials or meta-analyses on whether both differ in their antidepressant efficacy are lacking. We aimed to meta-analytically compare the short-term efficacy of a single dose of IV and IN ketamine in adult patients with major depressive disorder (MDD) and included double-blind, randomized controlled trials published until February 2022 in our analyses. The main outcome was a response 24 h after the administration of a single dose of ketamine. A random-effects model was used to calculate odds ratios and confidence intervals. Differences in efficacy between intranasal and intravenous application were statistically assessed by calculating a z-test. A total of eleven studies, comprising 1340 patients, were included. Results showed, that while both IN and IV ketamine were associated with increased response rates, efficacy did not differ significantly between these routes. Heterogeneity and funnel plot asymmetry was found in the intranasal sample only. The results of the present meta-analysis corroborate the efficacy of both IN and IV application of ketamine for the treatment of MDD but suggest no difference between both routes of administration. Accordingly, future large-scale trials as well as direct comparative trials are needed to further investigate this question.