{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:02:49Z","timestamp":1764151369992,"version":"3.46.0"},"reference-count":48,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Lubiprostone and its active metabolite may activate prostaglandin receptors, raising concerns about an increased risk of headache. We performed a systematic review and meta\u2010analysis to identify whether lubiprostone increases the risk of headache.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To identify all relevant randomized controlled trials (RCTs), we comprehensively searched MEDLINE (via PubMed),\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      website and the Cochrane Central Register of Controlled Trials. The search focused on studies comparing lubiprostone\n                      <jats:italic>vs<\/jats:italic>\n                      . placebo or other laxatives. A DerSimonian\u2013Laird random\u2010effects model was utilized to estimate risk ratios (RRs) and 95% confidence intervals (CIs). A fixed\u2010effect method based on the Mantel\u2013Haenszel method was employed for analyses with 3 or fewer studies. Heterogeneity was assessed using the I\n                      <jats:sup>2<\/jats:sup>\n                      statistic, and the certainty of evidence was rated using the GRADE approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010six studies were examined in the analysis. The incidence of headache was 5.3% for lubiprostone and 3.2% for placebo or other laxatives. Lubiprostone increased the risk of headache (RR 1.32, 95% CI 1.02\u20131.71, I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%, 6265 patients, 26 RCTs, moderate certainty) relative to placebo or other laxatives. The risk of headache seemed to be consistently increased in both adults (RR 1.23, 95% CI 0.93\u20131.62, I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%, 5390 patients, 24 RCTs, moderate certainty) and children (RR 3.07, 95% CI 1.67\u20135.63, I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200984.4%, 875 patients, 2 RCTs, very low certainty).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results of this meta\u2010analysis suggest that lubiprostone treatment increases the risk of headache in adults.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70305","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T04:28:56Z","timestamp":1759465736000},"page":"3315-3322","source":"Crossref","is-referenced-by-count":0,"title":["Association between use of lubiprostone and headache: A systematic review and meta\u2010analysis of randomized controlled trials"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6244-1253","authenticated-orcid":false,"given":"Satoru","family":"Mitsuboshi","sequence":"first","affiliation":[{"name":"Department of Pharmacy Kaetsu Hospital  Niigata Japan"},{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Morizumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Ohno Memorial Hospital  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5706-613X","authenticated-orcid":false,"given":"Shungo","family":"Imai","sequence":"additional","affiliation":[{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Hori","sequence":"additional","affiliation":[{"name":"Division of Drug Informatics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-1177","authenticated-orcid":false,"given":"Kazumasa","family":"Kotake","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Zikei Hospital\/Zikei Institute of Psychiatry  Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656560802631319"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/JGH.16844"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2012.708732"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u2010230X\u201012\u2010156\/FIGURES\/3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/BJP.2008.84"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.137"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/S10194\u2010021\u201001377\u20106\/FIGURES\/2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1468\u20102982.2008.01748.X"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEULET.2011.10.050"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(08)70062\u20100"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/BMJ.N71"},{"volume-title":"Cochrane handbook for systematic reviews of interventions version 6.5","year":"2024","author":"Higgins J","key":"e_1_2_9_13_1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.AD"},{"key":"e_1_2_9_15_1","unstructured":"GRADEpro GDT:GRADEpro Guideline Development Tool [Software]. 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