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

Roger S McIntyre, Isabelle P. Carvalho, Leanna M.W. Lui, Amna Majeed, P. Masand, Hartej Gill, Nelson B Rodrigues, Orly Lipsitz, A. Coles, Yena Lee, Jocelyn K. Tamura, M. Iacobucci, Lee Phan, Flora Nasri, Nikhita Singhal, Elizabeth Wong, Mehala Subramaniapillai, Rodrigo B. Mansur, R. Ho, Raymond W. Lam, Joshua D. Rosenblat

Journal of Affective Disorders November 1, 2020 DOI: 10.1016/j.jad.2020.06.050 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Peer reviewed
Population Adults with treatment-resistant depression
Topics Esketamine Ketamine
Citations 186
Key findings Intranasal ketamine or esketamine showed a large effect on depression symptoms at 24 hours and at 7-20 days, while intravenous and oral routes also showed effects at later time points, but no comparative conclusions could be drawn.

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 < 0.01). At 2-6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: -0.308-2.206, p = 0.139). At 7-20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499-1.538, p < 0.01). At 21-28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368-0.898, p < 0.01).

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.