{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:44:59Z","timestamp":1792633499913,"version":"4.5.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,26]],"date-time":"2024-05-26T00:00:00Z","timestamp":1716681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:p>\n                    Hydrocodone, tramadol, codeine, and oxycodone are commonly prescribed opioids that rely on activation by cytochrome P450 2D6 (CYP2D6). CYP2D6 inhibitors can significantly decrease CYP2D6 activity, leading to reduced generation of active metabolites, and impairing pain control. To understand this impact, we assessed emergency department (ED) visits in patients initiating these CYP2D6\u2010dependent opioids while on CYP2D6\u2010inhibitor antidepressants vs. antidepressants that do not inhibit CYP2D6. This retrospective cohort study included adult patients prescribed CYP2D6\u2010dependent opioids utilizing electronic health records data from the University of Florida Health (2015\u20132021). The association between ED visits and inhibitor exposure was tested using multivariable logistic regression. The primary analysis had 12,118 patients (72% female; mean (SD) age, 55 (13.4)) in the hydrocodone\/tramadol\/codeine cohort and 5,547 patients (64% female; mean (SD) age, 53.6 (14.2)) in the oxycodone cohort. Hydrocodone\/tramadol\/codeine\u2010treated patients exposed to CYP2D6\u2010inhibitor antidepressants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097,043) had a higher crude rate of pain\u2010related ED visits than those taking other antidepressants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095,075) (3.28% vs. 1.87%), with an adjusted odds ratio (aOR) of 1.75 (95% CI: 1.36 to 2.24). Similarly, in the oxycodone cohort, CYP2D6\u2010inhibitor antidepressant\u2010exposed individuals (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20093,206) had a higher crude rate of ED visits than individuals exposed to other antidepressants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092,341) (5.02% vs. 3.37%), with aOR of 1.70 (95% CI: 1.27\u20132.27). Similar findings were observed in secondary and sensitivity analyses. Our findings suggest patients with concomitant use of hydrocodone\/tramadol\/codeine or oxycodone and CYP2D6 inhibitors have more frequent ED visits for pain, which may be due to inadequate pain control.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3314","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T01:13:40Z","timestamp":1716772420000},"page":"1005-1012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Use of\n                    <scp>CYP2D6<\/scp>\n                    Inhibitors with\n                    <scp>CYP2D6<\/scp>\n                    Opioids: Association with Emergency Department Visits for Pain"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-7555","authenticated-orcid":false,"given":"Noor Ahmed","family":"Nahid","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6393-7288","authenticated-orcid":false,"given":"Caitrin W.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8861-6907","authenticated-orcid":false,"given":"Yu\u2010Jung Jenny","family":"Wei","sequence":"additional","affiliation":[{"name":"Division of Outcomes and Translational Sciences, College of Pharmacy The Ohio State University Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-9321","authenticated-orcid":false,"given":"Emily J.","family":"Cicali","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-1620","authenticated-orcid":false,"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7699-8183","authenticated-orcid":false,"given":"Roger B.","family":"Fillingim","sequence":"additional","affiliation":[{"name":"Department of Community Dentistry and Behavioral Science and Pain Research and Intervention Center of Excellence University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9847-1932","authenticated-orcid":false,"given":"Julie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida College of Pharmacy Gainesville Florida USA"},{"name":"Division of Cardiovascular Medicine University of Florida College of Medicine Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,26]]},"reference":[{"key":"e_1_2_10_1_1","unstructured":"Institute of Medicine (US) Committee on advancing pain research Cr and education. Relieving pain in America: a blueprint for transforming prevention care education and research(2011)."},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2015.05.002"},{"issue":"6","key":"e_1_2_10_3_1","first-page":"S205","article-title":"The management of persistent pain in older persons","volume":"50","author":"Persons APoPPiO","year":"2002","journal-title":"J. Am. Geriatr. Soc."},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.18472"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.1251"},{"key":"e_1_2_10_6_1","unstructured":"clincalc.com.The Top 300 of 2020<https:\/\/clincalc.com\/DrugStats\/Top300Drugs.aspx>. Accessed June 09 2023."},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","unstructured":"PharmVar.org.Pharmacogene Variation Consortium (PharmVar) at www.PharmVar.org (Gaedigk et\u00a0al. 2018 CPT 103:399; Gaedigk et\u00a0al. 2019 CPT 105:29). 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