Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/102344
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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 1469-5111 |
Statement of Responsibility: | 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 Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials.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 Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P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 meta-analysis |
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 (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1093/ijnp/pyv124 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1061043 http://purl.org/au-research/grants/nhmrc/1037196 http://purl.org/au-research/grants/nhmrc/1066280 http://purl.org/au-research/grants/nhmrc/1052555 |
Published version: | http://dx.doi.org/10.1093/ijnp/pyv124 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_102344.pdf | Published Version | 3.45 MB | Adobe PDF | View/Open |
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