{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:59:46Z","timestamp":1790495986141,"version":"4.1.0"},"reference-count":69,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2014,4,2]],"date-time":"2014-04-02T00:00:00Z","timestamp":1396396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:p>Pro-inflammatory cytokines (PICs) may play important pathophysiological roles in some forms of Major Depressive Disorder (MDD). The p38 MAPK inhibitor losmapimod (GW856553) attenuates the pro-inflammatory response in humans by reducing PIC production. Losmapimod (7.5 mg BD) was administered for 6 weeks in two randomised, placebo-controlled trials in subjects with MDD enriched with symptoms of loss of energy\/interest and psychomotor retardation (Studies 574 and 009). Primary efficacy endpoints were the Bech 6-item depression subscale of the HAMD-17 (the \u2018Bech,\u2019) for Study 009; and the Bech, Inventory of Depressive Symptomatology-Clinician Rated (IDS-C), HAMD-17, and Quick Inventory of Depressive Symptomatology (self-rated) (QIDS-SR) for Study 574. Key cytokine biomarker levels were also measured. Study 574 ( n=24) was terminated prematurely in light of emerging data from an internal study in rheumatoid arthritis. Efficacy results available at termination favoured losmapimod (Bech, 6 weeks: endpoint drug vs. placebo difference = \u22124.10; 95% CI, \u22127.36, \u22120.83; p=0.017). A subsequent study, Study 009 ( n=128), designed using a Bayesian approach based on a prior derived from Study 574, showed no advantage for losmapimod (Bech, 6 weeks: endpoint drug vs. placebo difference = 1.11; 95% credible interval, \u22120.22, 2.50). Biomarker data showed no significant changes. In conclusion 7.5 mg BID losmapimod was not effective in MDD.<\/jats:p>","DOI":"10.1177\/0269881114529377","type":"journal-article","created":{"date-parts":[[2014,4,3]],"date-time":"2014-04-03T21:09:38Z","timestamp":1396559378000},"page":"570-581","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Evaluation of antidepressant properties of the p38 MAP kinase inhibitor losmapimod (GW856553) in Major Depressive Disorder: Results from two randomised, placebo-controlled, double-blind, multicentre studies using a Bayesian approach"],"prefix":"10.1177","volume":"28","author":[{"given":"Amir","family":"Inamdar","sequence":"first","affiliation":[{"name":"Neurosciences Centre for Excellence in Drug Discovery, GlaxoSmithKline R&D Ltd, Harlow, Essex, UK"},{"name":"Present address: Takeda Development Centre Europe Ltd., London, UK"},{"name":"The first two authors equally contributed to the work here reported"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Merlo-Pich","sequence":"additional","affiliation":[{"name":"Neurosciences Centre for Excellence in Drug Discovery, GlaxoSmithKline R&D Ltd, Verona, Italy"},{"name":"Present address: Neuroscience DTA, F. 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