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Type: Journal article
Title: Effects of low-dose and very low-dose ketamine among patients with major depression: a systematic review and meta-analysis
Author: Xu, Y.
Hackett, M.
Carter, G.
Loo, C.
Gálvez, V.
Glozier, N.
Glue, P.
Lapidus, K.
McGirr, A.
Somogyi, A.
Mitchell, P.
Rodgers, A.
Citation: International Journal of Neuropsychopharmacology, 2016; 19(4):1-15
Publisher: Oxford University Press
Issue Date: 2016
ISSN: 1461-1457
Statement of
Ying Xu, Maree Hackett, Gregory Carter, Colleen Loo, Verònica Gálvez, Nick Glozier, Paul Glue, Kyle Lapidus, Alexander McGirr, Andrew A. Somogyi, Philip B. Mitchell, Anthony Rodgers
Abstract: Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1–0.4mg/kg i.v., and another assessed 0.1–0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6–7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2–5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety.
Keywords: Ketamine
major depression
Rights: © The Author 2015. Published by Oxford University Press on behalf of CINP. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/ijnp/pyv124
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