{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:47:42Z","timestamp":1791384462265,"version":"4.3.3"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,2,7]],"date-time":"2014-02-07T00:00:00Z","timestamp":1391731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with heartburn but without esophageal erosion respond less well to proton pump inhibitors (<jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>s). There is a growing body of evidence implicating the role of psychological comorbidities in producing reflux symptoms. Pain modulators improve symptoms in patients with other functional gastrointestinal disorders. We aimed to compare the efficacy of fluoxetine with omeprazole and placebo to achieve symptomatic relief in patients with heartburn and normal endoscopy who failed once daily <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>s.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Endoscopy\u2010negative patients with heartburn who failed once daily PPIs were randomly allocated to receive 6\u00a0weeks treatment of fluoxetine, omeprazole, or placebo. Random allocation was stratified according to ambulatory pH monitoring study. Percentage of heartburn\u2010free days and symptom severity was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Sixty patients with abnormal and 84 patients with normal pH test were randomized. Subjects receiving fluoxetine experienced more improvement in percentage of heartburn\u2010free days (median 35.7, IQR 21.4\u201357.1) than those on omeprazole (median 7.14, IQR 0\u201350, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001) or placebo (median 7.14, IQR 0\u201333.6, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). In normal pH subgroup, fluoxetine was superior to both omeprazole and placebo regarding percentage of heartburn\u2010free days (median improvement, 57.1, IQR 35.7\u201357.1 <jats:italic>vs<\/jats:italic> 13.9, IQR, 0\u201345.6 and 7.14, 0\u201323.8, respectively, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), but no significant difference was observed between medications in abnormal pH subgroup.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Fluoxetine was superior to omeprazole for improving the symptoms of patients with heartburn and normal endoscopy who failed once daily <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>s. The superiority of fluoxetine was mostly attributed to those with normal esophageal pH rather than those with abnormal pH (ClinicalTrials.gov, number <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"DDBJ\/EMBL\/GenBank\" xlink:href=\"NCT01269788\">NCT01269788<\/jats:ext-link>).<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12313","type":"journal-article","created":{"date-parts":[[2014,2,7]],"date-time":"2014-02-07T07:57:19Z","timestamp":1391759839000},"page":"670-678","source":"Crossref","is-referenced-by-count":76,"title":["Comparing omeprazole with fluoxetine for treatment of patients with heartburn and normal endoscopy who failed once daily proton pump inhibitors: Double\u2010blind placebo\u2010controlled trial"],"prefix":"10.1111","volume":"26","author":[{"given":"M. R.","family":"Ostovaneh","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Johns Hopkins Medical Institutions Baltimore MD USA"},{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Saeidi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hajifathalian","sequence":"additional","affiliation":[{"name":"Department of Global Health and Population Harvard School of Public Health Harvard University Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Farrokhi\u2010Khajeh\u2010Pasha","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Fotouhi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics School of Public Health Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. S.","family":"Mirbagheri","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Emami","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Barzin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. A.","family":"Mirbagheri","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Internal Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.145581"},{"key":"e_1_2_10_3_1","first-page":"29","article-title":"How satisfied are chronic heartburn sufferers with their prescription medications? 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