{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:30:39Z","timestamp":1780410639673,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"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":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Concomitant use of central nervous system (CNS) medications frequently occurs in older adults with persistent opioid use. The risks of adverse outcomes associated with combinations of opioids, sedative hypnotics, or skeletal muscle relaxants have not been sufficiently described in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To compare the overall and incremental risk of (1) fall\u2010related injury and (2) all\u2010cause hospitalization associated with sedative hypnotics and skeletal muscle relaxants among older persistent opioid users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case\u2010time\u2010control study was conducted using administrative claims of adults ages \u226566\u00a0years with a history of persistent (\u226590\u00a0days) opioid use. Cases included those with first (1) emergency department, hospital, or outpatient visit for a fall\u2010related injury, or (2) all\u2010cause hospitalization. Exposure to CNS medications prior to the case event versus earlier periods, and the risk associated with CNS drug class combinations and sequence of use, was estimated using conditional logistic regression, adjusted for time trends and time\u2010varying covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 140,101 older persistent opioid users, 20,723 experienced fall\u2010related injury and 39,444 were hospitalized during follow\u2010up. Skeletal muscle relaxant use was associated with an increased risk of fall\u2010related injury (Odds ratio [OR] 1.28) and all\u2010cause hospitalization (OR 1.11). Statistically significant associations were observed for the joint effects of interactions involving skeletal muscle relaxants on fall\u2010related injury (with opioid: OR 1.25; with sedative hypnotic: OR 1.24), and interactions involving opioids on all\u2010cause hospitalization (with sedative hypnotic: OR 1.10; with skeletal muscle relaxant: OR 1.17). The addition of a skeletal muscle relaxant to an opioid regimen was associated with a 25% increased risk of fall\u2010related injury. Additions of other CNS medications did not have apparent incremental effects on the risk of all\u2010cause hospitalization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The excess risks of fall\u2010related injury and hospitalization associated with various combinations of CNS medications among older persistent opioid users should be considered in therapeutic decision making. Further research is needed to confirm these findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2612","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T10:29:04Z","timestamp":1627640944000},"page":"733-742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Risk of fall\u2010related injury and all\u2010cause hospitalization of select concomitant central nervous system medication prescribing in older adult persistent opioid users: A case\u2010time\u2010control analysis"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-8235","authenticated-orcid":false,"given":"Kellyn M.","family":"Moran","sequence":"first","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Systems, Outcomes and Policy University of Illinois at Chicago Chicago Illinois USA"},{"name":"Takeda Pharmaceutical Company Limited Lexington Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7744-3518","authenticated-orcid":false,"given":"Gregory S.","family":"Calip","sequence":"additional","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Systems, Outcomes and Policy University of Illinois at Chicago Chicago Illinois USA"},{"name":"Flatiron Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Systems, Outcomes and Policy University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Koronkowski","sequence":"additional","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Practice University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denys T.","family":"Lau","sequence":"additional","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Systems, Outcomes and Policy University of Illinois at Chicago Chicago Illinois USA"},{"name":"National Committee for Quality Assurance Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen T.","family":"Schumock","sequence":"additional","affiliation":[{"name":"College of Pharmacy Department of Pharmacy Systems, Outcomes and Policy University of Illinois at Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2016.02.014"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3776"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.3951"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2016.9225"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.280.2.147"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0035794"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.PHM.0000154904.83278.32"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2007.00571.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0b013e318169d03b"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.15767"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjopharm.2011.10.004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gln043"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.14930"},{"key":"e_1_2_9_15_1","unstructured":"U.S. Food and Drug Administration: Drug Safety Communications.FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. 31 Aug 2016. 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