{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:03:49Z","timestamp":1788545029482,"version":"build-2803163510"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antidepressants are associated with traumatic injury and are widely used with other medications. It remains unknown how drug\u2013drug\u2013drug interactions (3DIs) between antidepressants and two other drugs may impact potential injury risks associated with antidepressants. We aimed to generate hypotheses regarding antidepressant 3DI signals associated with elevated injury rates. Using 2000\u20132020 Optum's de\u2010identified Clinformatics Data Mart, we performed a self\u2010controlled case series study for each drug triad consisting of an antidepressant\u2009+\u2009codispensed drug (base\u2010pair) with a candidate interacting medication (precipitant). We included persons aged greater than or equal to 16\u2009years who (1) experienced an injury and (2) used a candidate precipitant, during base\u2010pair therapy. We compared injury rates during observation time exposed to the drug triad versus the base\u2010pair only, adjusting for time\u2010varying covariates. We calculated adjusted rate ratios (RRs) using conditional Poisson regression and accounted for multiple comparisons via semi\u2010Bayes shrinkage. Among 147,747 eligible antidepressant users with an injury, we studied 120,714 antidepressant triads, of which 334 (0.3%) were positively associated with elevated injury rates and thus considered potential 3DI signals. Adjusted RRs for signals ranged from 1.31 (1.04\u20131.65) for sertraline\u2009+\u2009levothyroxine with tramadol (vs. without tramadol) to 6.60 (3.23\u201313.46) for escitalopram\u2009+\u2009simvastatin with aripiprazole (vs. without aripiprazole). Nearly half of the signals (137, 41.0%) had adjusted RRs greater than or equal to 2, suggesting strong associations with injury. The identified signals may represent antidepressant 3DIs of potential clinical concern and warrant future etiologic studies to test these hypotheses.<\/jats:p>","DOI":"10.1111\/cts.13452","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T06:55:03Z","timestamp":1669186503000},"page":"326-337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antidepressant drug\u2013drug\u2013drug interactions associated with unintentional traumatic injury: Screening for signals in real\u2010world data"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-8153","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Hennessy","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Leonard Davis Institute of Health Economics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Brensinger","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren B.","family":"Bilker","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Dublin","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute  Seattle Washington USA"},{"name":"Department of Epidemiology, School of Public Health University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-2898","authenticated-orcid":false,"given":"Sophie P.","family":"Chung","sequence":"additional","affiliation":[{"name":"Epocrates Medical Information AthenaHealth, Inc.  Watertown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacie F.","family":"Bogar","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5092-9657","authenticated-orcid":false,"given":"Charles E.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Center for Real\u2010World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Leonard Davis Institute of Health Economics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1","article-title":"Prescription drug use in the United States, 2015\u20102016","volume":"334","author":"Martin CB","year":"2019","journal-title":"NCHS Data Brief"},{"key":"e_1_2_9_3_1","first-page":"1","article-title":"Antidepressant use among adults: United States, 2015\u20102018","volume":"377","author":"Brody DJ","year":"2020","journal-title":"NCHS Data Brief"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200926050-00002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2017.08.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/aft009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2011.03561.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-013-0120-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pnp.429"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.9740\/mhc.2016.01.035"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2195"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7048a1"},{"key":"e_1_2_9_13_1","unstructured":"National Highway Traffic Safety Administration.Multiple medications and vehicle crashes: Analysis of databases.https:\/\/trid.trb.org\/view\/863878. 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