{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:38:26Z","timestamp":1789540706296,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clin Psychol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Importance<\/jats:title><jats:p>More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short\u2010term and long\u2010term differences in cardiac and mortality outcomes between MOUD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016\u20102022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (<jats:italic>n<\/jats:italic>\u2009=\u200940,938)\u2014who were only prescribed methadone. (2) Buprenorphine cohort (<jats:italic>n<\/jats:italic>\u2009=\u200980,055)\u2014who were only prescribed buprenorphine. (3) Naltrexone cohort (<jats:italic>n<\/jats:italic>\u2009=\u20095,738)\u2014who were only prescribed naltrexone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Exposures<\/jats:title><jats:p>methadone, buprenorphine, or naltrexone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow\u2010up time frames (1\u2010month, 3\u2010month, 6\u2010month, 1\u2010year, 3\u2010year, and 5\u2010year) by comparing propensity\u2010score matched cohorts using Kaplan\u2010Meier survival analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity\u2010score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1\u2010month follow\u2010up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04\u22121.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75\u22123.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21\u22121.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23\u22121.38), long QT syndrome (HR: 3.14, 95% CI: 2.76\u22123.58), death (HR: 1.50, 95% CI: 1.41\u22121.59).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jclp.23582","type":"journal-article","created":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T05:51:21Z","timestamp":1692424281000},"page":"2869-2883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cardiac and mortality outcome differences between methadone, buprenorphine and naltrexone prescriptions in patients with an opioid use disorder"],"prefix":"10.1002","volume":"79","author":[{"given":"Lindsey","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Science, Health, and Society, Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan A.","family":"Berger","sequence":"additional","affiliation":[{"name":"Center for Science, Health, and Society, Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela B.","family":"Davis","sequence":"additional","affiliation":[{"name":"Center for Community Health Integration, Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Kaelber","sequence":"additional","affiliation":[{"name":"The Center for Clinical Informatics Research and Education, The MetroHealth System Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-4795","authenticated-orcid":false,"given":"Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"577","article-title":"A systematic review of the cardiotoxicity of methadone","volume":"14","author":"Alinejad S.","year":"2015","journal-title":"EXCLI Journal"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000353"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1547-5069.2003.tb00001.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2009.163"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14703"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.166.12.1280"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/00952990.2013.804525"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.16168"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2014.07.035"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2017.1270156"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.13425"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.038240"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.023482"},{"issue":"3","key":"e_1_2_10_15_1","first-page":"1070","article-title":"Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long\u2010term, methadone\u2010treated former heroin addicts","volume":"295","author":"Kling M. 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