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Mirtazapine is an atypical antidepressant with a well-known 5-HT<jats:sub>3<\/jats:sub> receptor antagonist property. This study, therefore, was undertaken to investigate whether compared to placebo, mirtazapine would be efficacious and safe in the treatment of patients with IBS-D.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>From November 2019 until July 2020, 67 patients meeting Rome IV criteria for IBS-D were randomized in a double-blind fashion into either the mirtazapine treatment group (<jats:italic>n<\/jats:italic>\u2009=\u200934) or the placebo treatment group (<jats:italic>n<\/jats:italic>\u2009=\u200933). Patients started with mirtazapine 15\u2009mg\/day at bedtime for one-week; after which the dose was increased to 30\u2009mg\/day for an additional 7-week. Outcomes included changes in the total IBS symptom severity score (IBS-SSS), Hospital anxiety and depression scale score (HADS), and IBS Quality of Life. Additionally, changes in the diary-based symptoms scores including pain, urgency of defecation, bloating, stool frequency, and\u00a0stool consistency based on the 7-point Bristol Stool Form Scale (BSFS), and a number of days per week with pain, urgency, diarrhea, or bloating, once during the 1-week run-in period, and once during the last week of treatment were recorded.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>All analyses were performed on an Intention-to-Treat (ITT) analysis data set. The results showed compared to placebo, mirtazapine is more efficacious in decreasing the severity of IBS symptoms (<jats:italic>P<\/jats:italic>-value\u2009=\u20090.002). Further, at the end of the treatment period, all diary-derived symptoms except bloating showed significantly more improvement in the mirtazapine-treated subjects compared to the placebo-treated subjects. While was well-tolerated, mirtazapine also significantly improved the patients\u2019 quality of life (<jats:italic>P<\/jats:italic>-value\u2009=\u20090.04) and anxiety symptoms (<jats:italic>P<\/jats:italic>-value\u2009=\u20090.005).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overall, mirtazapine seems to have a potential benefit in the treatment of patients with IBS-D, particularly those with concomitant psychological symptoms. However, further studies are warranted to determine whether these findings are replicated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Trial registration: Registration number at Iranian Registry of Clinical Trials: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.irct.ir\/trial\/42843\">IRCT20120215009014N311<\/jats:ext-link>. Registration date: 2019-10-21.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13030-021-00205-2","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T13:04:25Z","timestamp":1612357465000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A randomized, double-blind, placebo-controlled study to assess efficacy of mirtazapine for the treatment of diarrhea predominant irritable bowel syndrome"],"prefix":"10.1186","volume":"15","author":[{"given":"Alireza","family":"Khalilian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davoud","family":"Ahmadimoghaddam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Saki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younes","family":"Mohammadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Mehrpooya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"205_CR1","first-page":"71","volume":"6","author":"C Canavan","year":"2014","unstructured":"Canavan C, West J, Card T. 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