{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:28:42Z","timestamp":1778610522635,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>Methadone, a widely prescribed medication for chronic pain and opioid addiction, is associated with respiratory depression and increased predisposition for torsades de pointes, a potentially fatal arrhythmia. Most methadone\u2010related deaths occur during sleep. The objective of this study was to determine whether methadone\u2019s arrhythmogenic effects increase during sleep, with a focus on cardiac repolarization instability using QT variability index (QTVI), a measure shown to predict arrhythmias and mortality. Sleep study data of 24 patients on chronic methadone therapy referred to a tertiary clinic for overnight polysomnography were compared with two matched groups not on methadone: 24 patients referred for overnight polysomnography to the same clinic (clinic group), and 24 volunteers who had overnight polysomnography at home (community group). Despite similar values for heart rate, heart rate variability, corrected QT interval, QTVI, and oxygen saturation (SpO<jats:sub>2<\/jats:sub>) when awake, patients on methadone had larger QTVI (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.015 vs. clinic, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 vs. community) and lower SpO<jats:sub>2<\/jats:sub> (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.008 vs. clinic, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013 vs. community) during sleep, and the increase in their QTVI during sleep vs. wakefulness correlated with the decrease in SpO<jats:sub>2<\/jats:sub> (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u22120.54, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013). QTVI positively correlated with methadone dose during sleep (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.51, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.012) and wakefulness (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.73, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). High\u2010density ectopy (&gt;\u00a01,000 premature beats per median sleep period), a precursor for torsades de pointes, was uncommon but more frequent in patients on methadone (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.039). This study demonstrates that chronic methadone use is associated with increased cardiac repolarization instability. Methadone\u2019s pro\u2010arrhythmic impact may be mediated by sleep\u2010related hypoxemia, which could explain the increased nocturnal mortality associated with this opioid.<\/jats:p>","DOI":"10.1002\/cpt.2368","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T15:51:11Z","timestamp":1626709871000},"page":"1066-1074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Methadone Destabilizes Cardiac Repolarization During Sleep"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-2479","authenticated-orcid":false,"given":"Soroosh","family":"Solhjoo","sequence":"first","affiliation":[{"name":"Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naresh M.","family":"Punjabi","sequence":"additional","affiliation":[{"name":"Leonard M. Miller School of Medicine University of Miami Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrada E.","family":"Ivanescu","sequence":"additional","affiliation":[{"name":"Montclair State University Montclair New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciprian","family":"Crainiceanu","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Gaynanova","sequence":"additional","affiliation":[{"name":"Texas A&amp;M University College Station Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassie","family":"Wicken","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Chester","family":"Buckenmaier","sequence":"additional","affiliation":[{"name":"F. Edward H\u00e9bert School of Medicine Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark C.","family":"Haigney","sequence":"additional","affiliation":[{"name":"F. Edward H\u00e9bert School of Medicine Bethesda Maryland USA"},{"name":"Military Cardiovascular Outcomes Research (MiCOR) Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-009-1225-0"},{"key":"e_1_2_11_2_1","first-page":"1","article-title":"Baseline and 1\u2010year longitudinal data from the National Restless Legs Syndrome Opioid Registry","volume":"44","author":"Winkelman J.W.","year":"2021","journal-title":"Sleep"},{"key":"e_1_2_11_3_1","first-page":"1","article-title":"Drugs most frequently involved in drug overdose deaths: United States, 2011\u20132016","volume":"67","author":"Hedegaard H.","year":"2018","journal-title":"Natl. Vital Stat. 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