{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:17:25Z","timestamp":1789499845652,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T00:00:00Z","timestamp":1326758400000},"content-version":"vor","delay-in-days":4763,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[1999,1,2]]},"abstract":"<jats:p><jats:bold>Study Objectives.<\/jats:bold> To examine the effect of three titration schedules on the tolerability of tramadol, and to determine whether slow titration would reduce the frequency of drug discontinuation due to adverse events.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Multicenter, outpatient, double\u2010blind, parallel study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Twenty\u2010eight outpatient study centers.<\/jats:p><jats:p><jats:bold>Subjects.<\/jats:bold> Four hundred sixty\u2010five patients with chronic joint pain<\/jats:p><jats:p><jats:bold>Interventions.<\/jats:bold> Patients were randomized into one of four treatment groups for 14 days: placebo, or tramadol dosage titrated at 1, 4, or 10 days to achieve the study target dosage of 200 mg\/day. They continued taking their dosage of nonsteroidal antiinflammatory drug during the study. Each group was examined to determine if slower titration resulted in a statistically significant trend toward fewer discontinuations due to nausea and\/or vomiting and dizziness and\/or vertigo. Discontinuation due to any adverse event was similarly analyzed. If the trend was statistically significant, pairwise comparisons were performed to determine the statistical significance among titration rates.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> A statistically significant trend was seen toward fewer discontinuations as a result of nausea\/vomiting, dizziness\/vertigo, and any adverse event as the titration rate decreased. Patients with 10\u2010day titration rate required the fewest discontinuations, and this rate was statistically significantly different from both the 1\u2010 and 4\u2010day rates for discontinuations.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> A slower rate of initiating tramadol therapy (50\u2010mg increments every 3 days) improved tolerability with significantly fewer discontinuations due to dizziness or vertigo.<\/jats:p>","DOI":"10.1592\/phco.19.1.88.30515","type":"journal-article","created":{"date-parts":[[2004,4,26]],"date-time":"2004-04-26T05:49:43Z","timestamp":1082958583000},"page":"88-93","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Slowing the Initial Titration Rate of Tramadol Improves Tolerability"],"prefix":"10.1002","volume":"19","author":[{"given":"Gary E.","family":"Ruoff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,1,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90118-H"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90117-G"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(89)80060-5"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-109-5-353"},{"key":"e_1_2_1_6_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0022-3565(25)11227-5","article-title":"Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an \u201catypical\u201d opioid analgesic","volume":"260","author":"Raffa R.B.","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_7_2","first-page":"1278","article-title":"Bioavailability of enteral tramadol formulations. First communication: capsules","volume":"36","author":"Lintz W.","year":"1986","journal-title":"Arzneimittelforschung"},{"issue":"9","key":"e_1_2_1_8_2","first-page":"S86","article-title":"Comparison of tramadol and ibuprofen for the chronic pain of osteoarthritis","volume":"40","author":"Dalgin P.","year":"1997","journal-title":"Arthritis Rheum"},{"issue":"9","key":"e_1_2_1_9_2","first-page":"S86","article-title":"Ultram (tramadol HCl) maintains relief of osteoarthritis (OA) pain when substituted for high dose naproxen","volume":"40","author":"Schnitzer T.","year":"1997","journal-title":"Arthritis Rheum"},{"key":"e_1_2_1_10_2","first-page":"1358","article-title":"Efficacy and safety of tramadol in breakthrough musculoskeletal pain attributed to OA","volume":"25","author":"Roth S.H.","year":"1998","journal-title":"J Rheumatol"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0011-393X(05)80748-9"},{"key":"e_1_2_1_12_2","first-page":"177","article-title":"The role of tramadol in the management of musculoskeletal pain","volume":"13","author":"Katz W.A.","year":"1995","journal-title":"Today's Therapeutic Trends"},{"key":"e_1_2_1_13_2","first-page":"542","article-title":"Alternative dosing for tramadol aids effectiveness [letter]","volume":"30","author":"Barkin R.L.","year":"1995","journal-title":"Formulary"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209103271101"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1991.tb03743.x"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-114-4-257"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908033210507"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/25.1.29"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.19.1.88.30515","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.19.1.88.30515","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:17:36Z","timestamp":1761041856000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.19.1.88.30515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1,2]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,1,2]]}},"alternative-id":["10.1592\/phco.19.1.88.30515"],"URL":"https:\/\/doi.org\/10.1592\/phco.19.1.88.30515","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1,2]]},"assertion":[{"value":"2012-01-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}