{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T12:49:22Z","timestamp":1788526162632,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Histamine 2\u2010receptor antagonists (H2RAs) commonly treat gastroesophageal reflux disease (GERD). However, tachyphylaxis, defined as the rapid reduction of efficacy, is frequently reported and remains poorly understood. This investigation performed a scoping review on the decrease in H2RA efficacy with repeat dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Source<\/jats:title>\n                    <jats:p>Following PRISMA\u2010ScR guidelines, we systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Database through August 27, 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Review Method<\/jats:title>\n                    <jats:p>Two reviewers independently screened studies and extracted data on mechanisms, impact, and management strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>While H2RAs effectively reduce gastric acid secretion, continuous dosing leads to tachyphylaxis of unclear etiology. Initial H2RA treatment increases the percentage of time intragastric pH is &gt;\u20094, from 8% to 38%. Tachyphylaxis begins by the second dose, 2, with an 11.2% reduction in efficacy by day 3. By day 15, tachyphylaxis results in a 13.0%\u201327.5% (mean: 20.3%) decrease in efficacy, after which no further reduction in effectiveness occurs. In comparison, once\u2010daily proton pump inhibitors maintain a daily intragastric pH of 63% above 4, with no tachyphylaxis observed after 14\u2009days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Tachyphylaxis is a well\u2010documented, diminished treatment effect observed across the entire class of H2RAs. It typically begins by day 2 and plateaus quickly, resulting in up to a quarter decrease in absolute efficacy. The precise mechanisms underlying H2RA tachyphylaxis remain uncertain. H2RAs should not be prescribed as first\u2010line agents for the management of frequent GERD or routinely added in cases of incomplete response to PPIs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70337","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T12:22:56Z","timestamp":1767010976000},"page":"2412-2425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histamine 2\u2010Receptor Antagonists Tachyphylaxis: A Scoping Review"],"prefix":"10.1002","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-3402","authenticated-orcid":false,"given":"James H.","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery The Johns Hopkins University School of Medicine  Baltimore Maryland 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