{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:59:45Z","timestamp":1782982785564,"version":"3.54.5"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,9,12]],"date-time":"2020-09-12T00:00:00Z","timestamp":1599868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008368","name":"Danish Rheumatism Association","doi-asserted-by":"publisher","award":["R155-A4821-B1326"],"award-info":[{"award-number":["R155-A4821-B1326"]}],"id":[{"id":"10.13039\/100008368","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study explores dose\u2013response relationships when treating fibromyalgia with low-dose naltrexone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A single-blinded clinical trial was carried out using the \u201cup-and-down\u201d method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Subjects<\/jats:title>\n                  <jats:p>Subjects included women with a diagnosis of fibromyalgia aged 18\u201360\u2009years who had been referred to treatment at a public pain clinic at a Danish university hospital.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The test doses were in the range 0.75\u20136\u2009mg, and the dosing interval was 0.75\u2009mg. The method was sequential and allowed predicting the dose effective in 50% (ED50) and 95% (ED95) of the subjects when the dose had shifted direction 10 times, and six pairs of \u201cup-and-down\u201d data were available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 27 subjects were included in the study; two subjects were withdrawn. After inclusion of 25 evaluable subjects, the dose estimates were calculated as 3.88\u2009mg for ED50 and 5.40\u2009mg for ED95. As a secondary outcome, the effects on 10 common fibromyalgia symptoms were evaluated. A high interindividual variation was observed both in the symptom presentation at baseline and in which symptoms were reduced by low-dose naltrexone.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study is the first to explore dose\u2013response relationships in the treatment of fibromyalgia with low-dose naltrexone. Future placebo-controlled randomized clinical trials are needed, and according to our findings, 4.5\u2009mg, which has previously been used, seems to be a relevant test dose. We recommend that future studies include additional nonpain fibromyalgia symptoms as outcome measures.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pm\/pnaa001","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T12:09:49Z","timestamp":1577966989000},"page":"2253-2261","source":"Crossref","is-referenced-by-count":31,"title":["Low-Dose Naltrexone for the Treatment of Fibromyalgia: Investigation of Dose\u2013Response Relationships"],"prefix":"10.1093","volume":"21","author":[{"given":"Karin","family":"Bruun-Plesner","sequence":"first","affiliation":[{"name":"Pain Research Group, Pain Centre, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"},{"name":"Open Patient Data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Rune","family":"Blichfeldt-Eckhardt","sequence":"additional","affiliation":[{"name":"Pain Research Group, Pain Centre, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik Bjarke","family":"Vaegter","sequence":"additional","affiliation":[{"name":"Pain Research Group, Pain Centre, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joergen T","family":"Lauridsen","sequence":"additional","affiliation":[{"name":"Department of Business and Economics, University of Southern Denmark, Odense, 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