{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:55:18Z","timestamp":1792065318881,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    The analgesic effectiveness of several opioids depends on CYP2D6\u2010mediated metabolism to more active opioid receptor agonists. CYP2D6 activity is impacted by genetic variability and medications that inhibit CYP2D6. We conducted a pragmatic, multi\u2010center, randomized, controlled trial to determine whether CYP2D6\u2010guided opioid prescribing improves chronic pain. Participants were adults recruited from primary care or pain specialty clinics with at least 3\u2009months of chronic pain treated or considered for treatment with tramadol, hydrocodone, or codeine. Participants were randomized to the usual care or CYP2D6\u2010guided arm, in which\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    pharmacogenetic testing was performed. Healthcare professionals were recommended to avoid tramadol, hydrocodone, or codeine in patients with CYP2D6 intermediate or poor or ultra\u2010rapid (for safety) metabolizer phenotypes based on either genotype or drug interactions. The primary outcome was the change in composite pain intensity scores from baseline to 3\u2009months. Of 1048 enrolled participants, 282 had an actionable CYP2D6 phenotype. In this group, CYP2D6\u2010guided recommendations did not improve the change in composite pain intensity scores from baseline to 3\u2009months compared with usual care (mean [SD] \u22120.8 [2.4] vs. \u22120.7 [2.3]) or improve drug\u2010gene concordance (26.8% vs. 27.1%) in the CYP2D6\u2010guided versus usual care arm, respectively. In an exploratory analysis, participants whose therapy changed to align with their CYP2D6 phenotype had significantly improved pain scores. In conclusion, incorporating CYP2D6\u2010guided recommendations for opioid therapy into routine practice did not change prescribing sufficiently to assess its impact on chronic pain control, suggesting that EHR\u2010integrated CYP2D6 guidance is insufficient to change opioid prescribing for chronic pain.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70505","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:22:14Z","timestamp":1792063334000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>CYP2D6<\/i>\n                    <\/scp>\n                    \u2010Guided Opioid Therapy for Chronic Pain: A Multi\u2010Center Pragmatic Randomized Controlled Trial"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3849-374X","authenticated-orcid":false,"given":"Todd C.","family":"Skaar","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-8339","authenticated-orcid":false,"given":"Rachel A.","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Clinical Research Unit Duke University School of Medicine, Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger B.","family":"Fillingim","sequence":"additional","affiliation":[{"name":"Department of Community Dentistry and Behavioral Science University of Florida College of Dentistry  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-5651","authenticated-orcid":false,"given":"John T.","family":"Callaghan","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri L.","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Division of Nephrology &amp; Hypertension Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Veterans Health Administration VA Tennessee Valley Health Care System Geriatric Research, Education and Clinical Center (GRECC), and VETWISE\u2010LHS Center of Innovation  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrishikesh","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-5415","authenticated-orcid":false,"given":"Jordan F.","family":"Baye","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice South Dakota State University  Brookings South Dakota USA"},{"name":"Sanford Imagenetics, Sanford Health  Sioux Falls South Dakota 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, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-2876","authenticated-orcid":false,"given":"Michael T.","family":"Eadon","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Division of Nephrology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica N.","family":"Elwood","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0673-7866","authenticated-orcid":false,"given":"Lindsay J.","family":"Hines","sequence":"additional","affiliation":[{"name":"Department of Psychology University of North Dakota  Grand Forks North Dakota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0096-0293","authenticated-orcid":false,"given":"Khoa A.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Institute for Health Equity Research Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-345X","authenticated-orcid":false,"given":"Marc","family":"Rosenman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Ann &amp; 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Lurie Children's Hospital of Chicago and Feinberg School of Medicine, Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3804-5453","authenticated-orcid":false,"given":"Azita","family":"Sadeghpour","sequence":"additional","affiliation":[{"name":"Duke Precision Medicine Program, Department of Medicine Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-9335","authenticated-orcid":false,"given":"Saskia","family":"Shuman","sequence":"additional","affiliation":[{"name":"The Institute for Family Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9984-2088","authenticated-orcid":false,"given":"Rajbir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Meharry Medical College  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-9811","authenticated-orcid":false,"given":"Emma M.","family":"Tillman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2900-8140","authenticated-orcid":false,"given":"Christina M.","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Duke University School of Medicine  Durham North Carolina USA"},{"name":"Division of Nephrology, Department of Medicine Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-4700","authenticated-orcid":false,"given":"Carol R.","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Institute for Health Equity Research Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-5179","authenticated-orcid":false,"given":"Deepak","family":"Voora","sequence":"additional","affiliation":[{"name":"Department of Medicine, Clinical Research Unit Duke University School of Medicine, Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-7855","authenticated-orcid":false,"given":"Lori A.","family":"Orlando","sequence":"additional","affiliation":[{"name":"Duke Precision Medicine Program, Department of Medicine Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh F.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-5292","authenticated-orcid":false,"given":"Larisa H.","family":"Cavallari","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine, College of Pharmacy 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, College of Pharmacy University of Florida  Gainesville Florida USA"},{"name":"Clinical and Translational Science Institute The Ohio State University  Columbus Ohio USA"},{"name":"Department of Internal Medicine, College of Medicine The Ohio State University  Columbus Ohio USA"},{"name":"Department of Pharmaceutics &amp; Pharmacology, College of Pharmacy The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-0156","authenticated-orcid":false,"given":"Paul R.","family":"Dexter","sequence":"additional","affiliation":[{"name":"Regenstrief Institute, Inc.  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