{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:17:54Z","timestamp":1782785874992,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1TR001415"],"award-info":[{"award-number":["TL1TR001415"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine effective dose strategies for nortriptyline\u2013topiramate (NT) and verapamil\u2013paroxetine (VP) combinations for tinnitus treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This secondary analysis examined data from an 8\u2010week, randomized, double\u2010blind, placebo\u2010controlled trial (RCT) evaluating treatment outcomes in 41 patients. Tinnitus Functional Index (TFI) scores were used as the primary outcome measure, administered at baseline, Week 4, and Week 8 to assess achievement of minimal clinically important differences (MCID) of 13\u2010point reduction. Descriptive statistics were employed to characterize treatment responses and assess dose\u2013response relationships.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the NT group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200919), 42% of the participants achieved a reduction in TFI scores meeting MCID with a mean dose of 44\u2009\u00b1\u200912\u2009mg nortriptyline plus 59\u2009\u00b1\u200916\u2009mg topiramate, all showing greater than 15% improvement. In the VP group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922), 41% reached MCID with a mean of 207\u2009\u00b1\u200936\u2009mg verapamil plus 28\u2009\u00b1\u20095\u2009mg paroxetine. Of these, 88.9% showed at least a 15% improvement in TFI. Early responders who achieved MCID by the midpoint of the trial required continued dose escalations due to limited improvement in weekly VAS scores afterward. However, subsequent TFI changes were not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both NT and VP regimens effectively reduce tinnitus severity in approximately half of the patients at moderate doses within 8\u2009weeks. However, long\u2010term effects may not have been fully captured, particularly among late improvers.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Level of Evidence:<\/jats:bold>\n                      2.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.32338","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:33:31Z","timestamp":1751193211000},"page":"4348-4354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimal Dosing of Nortriptyline\u2013Topiramate and Verapamil\u2013Paroxetine Combinations in Tinnitus Treatment"],"prefix":"10.1002","volume":"135","author":[{"given":"Ella J.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Tawk","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha Luc\u00eda","family":"Guti\u00e9rrez P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3585-698X","authenticated-orcid":false,"given":"Mehdi","family":"Abouzari","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-5207","authenticated-orcid":false,"given":"Hamid R.","family":"Djalilian","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery University of California  Irvine California USA"},{"name":"Department of Biomedical Engineering University of California  Irvine California USA"},{"name":"Department of Neurosurgery University of California  Irvine California 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