The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis.
R. Mcintyre, Isabelle P. Carvalho, L. Lui, Amna Majeed, P. Masand, H. Gill, Nelson B Rodrigues, Orly Lipsitz, A. Coles, Yena Lee, Jocelyn K. Tamura, M. Iacobucci, Lee Phan, F. Nasri, Nikhita Singhal, Elizabeth Wong, M. Subramaniapillai, R. Mansur, R. Ho, R. Lam, J. Rosenblat
Journal of Affective Disorders November 1, 2020 DOI: 10.1016/j.jad.2020.06.050 via Semantic Scholar
Summary
Ketamine is a rapid and effective treatment for adults with treatment-resistant depression, but different formulations and routes of delivery vary in effect size. A meta-analysis of studies found that intranasal ketamine or esketamine had a large effect on depression symptoms at 24 hours and again at 7-20 days. Intravenous ketamine or esketamine showed a large but not statistically significant effect at 2-6 days. Oral ketamine had a moderate effect at 21-28 days. No conclusions about which formulation or route is best could be drawn because direct comparisons are lacking. More studies with larger samples are needed, especially for oral ketamine.
Study at a glance
| Characteristics | Meta-analysis Peer reviewed |
|---|---|
| Population | Adults with treatment-resistant depression |
| Keywords | Medicine |
| Citations | 186 |
| Key finding | 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.