{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T01:44:26Z","timestamp":1786671866750,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,25]],"date-time":"2022-12-25T00:00:00Z","timestamp":1671926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016568","name":"Nippon Zoki Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016568","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pain Practice"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>We investigated the efficacy and safety of twice\u2010daily bilayer sustained\u2010release tramadol hydrochloride tablets (35% immediate\u2010release; 65% sustained\u2010release) in patients with postherpetic neuralgia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a Phase III treatment\u2010withdrawal study with 1\u20134\u2010week dose\u2010escalation, 1\u2010week fixed\u2010dose, and 4\u2010week randomized, double\u2010blind, placebo\u2010controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged \u226520\u2009years, \u22653\u00a0months after the onset of herpes zoster with localized, persistent pain despite fixed\u2010dose analgesics for \u22652\u2009weeks before enrollment were eligible. Patients started tramadol at 100\u2009mg\/day and its dose escalated to a maximum of 400\u2009mg\/day to achieve a reduction in their Numeric Rating Scale (NRS) for pain of \u22652 points. Eligible patients were randomized to continue tramadol or switched to placebo for 4\u2009weeks (double\u2010blind period). Patients were withdrawn due to inadequate analgesia (NRS deteriorated on \u22652 consecutive days) or their request.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 252 patients started tramadol and 173 were randomized (tramadol: 85; placebo: 88). Tramadol was superior to placebo for the primary endpoint (time from randomization to an inadequate analgesic effect) with log\u2010rank test<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0005. The hazard ratio was 0.353 (95% confidence interval\u00a00.190\u20130.657) in favor of tramadol and fewer patients in the tramadol group experienced inadequate analgesic effects (16.9% vs. 39.8%). Adverse events in \u226510% of patients in the open\u2010label period were constipation (43.8%), nausea (34.9%), somnolence (18.5%), and dizziness (11.6%). The frequencies of adverse events in the double\u2010blind period were similar in both groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sustained\u2010release tramadol tablets with an immediate\u2010release component are effective and well tolerated for managing postherpetic neuralgia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/papr.13190","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T20:29:07Z","timestamp":1670444947000},"page":"277-289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and safety of<scp>twice\u2010daily<\/scp>tramadol hydrochloride bilayer<scp>sustained\u2010release<\/scp>tablets with an immediate release component for postherpetic neuralgia: Results of a Phase<scp>III<\/scp>, randomized,<scp>double\u2010blind<\/scp>,<scp>placebo\u2010controlled<\/scp>,<scp>treatment\u2010withdrawal<\/scp>study"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3996-0039","authenticated-orcid":false,"given":"Shinichi","family":"Kawai","sequence":"first","affiliation":[{"name":"Department of Inflammation &amp; Pain Control Research Toho University School of Medicine Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Sakurashinmachi Pain Clinic Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ito","sequence":"additional","affiliation":[{"name":"Tachikawa Dermatology Clinic Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Fukuuchi","sequence":"additional","affiliation":[{"name":"Fukuuchi Pain Clinic Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideshi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Nippon Zoki Pharmaceutical Co., Ltd. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Nippon Zoki Pharmaceutical Co., Ltd. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Nippon Zoki Pharmaceutical Co., Ltd. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Nippon Zoki Pharmaceutical Co., Ltd. Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v10110609"},{"key":"e_1_2_13_3_1","first-page":"656","article-title":"Herpes zoster and postherpetic neuralgia: prevention and management","volume":"96","author":"Saguil A","year":"2017","journal-title":"Am Fam Physician"},{"key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.4103\/JCAS.JCAS_45_20","article-title":"Post\u2010herpetic neuralgia: a systematic review of current interventional pain management strategies","volume":"13","author":"Aggarwal A","year":"2020","journal-title":"J Cutan Aesthet Surg"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.36076\/ppj\/2019.22.209"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1494"},{"issue":"6","key":"e_1_2_13_8_1","article-title":"Tramadol for neuropathic pain in adults","volume":"6","author":"Duehmke RM","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"e_1_2_13_10_1","first-page":"66","volume-title":"Guidelines for the pharmacologic management of neuropathic pain, second edition","author":"Committee for the Guidelines for the Pharmacologic Management of Neuropathic Pain of Japan Society of Pain Clinicians","year":"2016"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00020-4"},{"issue":"2","key":"e_1_2_13_12_1","first-page":"34","article-title":"Treatment of post\u2010herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine","volume":"53","author":"G\u00f6bel H","year":"1997","journal-title":"Drugs"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.2217\/pme.12.43"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1533-2500.2012.00583.x"},{"key":"e_1_2_13_15_1","first-page":"503","article-title":"A phase III clinical trial of NS\u201024 (controlled\u2010release tramadol hydrochloride tablets) in patients with chronic post\u2010herpetic neuralgia\u2010a randomized, double\u2010blind, comparative study with placebo (enriched enrollment randomized withdrawal design)","volume":"31","author":"Ogawa S","year":"2015","journal-title":"J Clin Ther Med."},{"key":"e_1_2_13_16_1","first-page":"513","article-title":"A phase III clinical trial of NS\u2010315 (tramadol hydrochloride) in patients with chronic post\u2010herpetic neuralgia\u2013a randomized, double\u2010blind, comparative study with placebo (enriched enrollment randomized withdrawal design)","volume":"29","author":"Ogawa S","year":"2013","journal-title":"J Clin Ther Med"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S49502"},{"key":"e_1_2_13_18_1","unstructured":"Nippon Zoki Pharmaceutical Co. Ltd.Twotram\u00ae (tramadol) tablets 50 mg 100 mg 150 mg. Interview Form August 2022 (7th Edition). Available from:https:\/\/www.info.pmda.go.jp\/go\/interview\/1\/530288_1149038G2026_1_081_1F.pdf. Accessed 18 Oct 2022 [in Japanese]."},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-022-01139-5"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(01)00349-9"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000055433.55136.55"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-016-0548-x"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(98)00095-X"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(98)00096-1"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2003.11.006"},{"key":"e_1_2_13_26_1","first-page":"401","article-title":"Tramadol extended\u2010release in the management of chronic pain","volume":"3","author":"McCarberg B","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjopharm.2012.09.004"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.5055\/jom.2008.0013"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0897190013504957"}],"container-title":["Pain Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/papr.13190","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/papr.13190","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/papr.13190","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T01:44:14Z","timestamp":1728524654000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/papr.13190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,25]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/papr.13190"],"URL":"https:\/\/doi.org\/10.1111\/papr.13190","archive":["Portico"],"relation":{},"ISSN":["1530-7085","1533-2500"],"issn-type":[{"value":"1530-7085","type":"print"},{"value":"1533-2500","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,25]]},"assertion":[{"value":"2022-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}