{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:37:21Z","timestamp":1789141041082,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["intramural"],"award-info":[{"award-number":["intramural"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>(<jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>)\u2010ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment\u2010resistant bipolar depression (<jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>). The genetic, pharmacological and biochemical differences between ketamine responders and non\u2010responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non\u2010targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non\u2010response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Plasma samples from 22 <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content> patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo\u2010controlled crossover study and the samples were obtained 230\u2009min post\u2010administration at which time the patients were categorized as responders or non\u2010responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non\u2010responders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial \u03b2\u2010oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury &amp; Beyond. To view the other articles in this issue visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue-8\">http:\/\/dx.doi.org\/10.1111\/bph.2014.171.issue\u20108<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12494","type":"journal-article","created":{"date-parts":[[2014,3,29]],"date-time":"2014-03-29T00:04:15Z","timestamp":1396051455000},"page":"2230-2242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response\u2010related difference in mitochondrial networks"],"prefix":"10.1111","volume":"171","author":[{"given":"A","family":"Villase\u00f1or","sequence":"first","affiliation":[{"name":"Center for Metabolomics and Bioanalysis (CEMBIO) Facultad de Farmacia Universidad CEU San Pablo  Madrid 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