{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:50Z","timestamp":1787027030986,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T00:00:00Z","timestamp":1650412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Methadone is associated with ventricular dysrhythmias and sudden death. Serotonin reuptake inhibitors (SRIs) may increase the risk of these events either by inhibiting metabolism of methadone\u2019s proarrhythmic (S)-enantiomer, additive QT interval prolongation, or both. We sought to determine whether certain SRIs were associated with a higher risk of methadone-related ventricular dysrhythmias or sudden death.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We conducted a nested case-control study of Ontario residents receiving methadone between April 1, 1996 and December 31, 2017. Cases, defined as patients who died of sudden cardiac death or were hospitalized with a ventricular dysrhythmia while on methadone, were matched with up to four controls who also received methadone on age, sex, and a disease risk score. We determined the odds ratio (OR) and\n                    <jats:italic>p<\/jats:italic>\n                    -value functions for the association between methadone-related cardiotoxicity and treatment with SRIs known to inhibit metabolism of (S)-methadone (paroxetine, fluvoxamine, sertraline) or prolong the QT interval (citalopram and escitalopram). Patients who were not treated with an SRI served as the reference group.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    During the study period, we identified 626 cases and 2,299 matched controls. Following multivariable adjustment, we found that recent use of sertraline, fluvoxamine or paroxetine (adjusted OR 1.30; 95% confidence intervals [CI] 0.90\u20131.86) and citalopram and escitalopram (adjusted OR 1.26; 95% CI 0.97\u20131.63) were associated with small increases in the risk methadone-related cardiac toxicity, an assertion supported by the corresponding\n                    <jats:italic>p<\/jats:italic>\n                    -value functions.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Interpretation:<\/jats:bold>\n                    Certain SRIs may be associated with a small increase in cardiac toxicity in methadone-treated patients.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.861953","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T01:17:03Z","timestamp":1650417423000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The Risk of Ventricular Dysrhythmia or Sudden Death in Patients Receiving Serotonin Reuptake Inhibitors With Methadone: A Population-Based Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Tony","family":"Antoniou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McCormack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Tadrous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Juurlink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1111\/j.1360-0443.2009.02549.x","article-title":"Prevalence and Clinical Relevance of Corrected QT Interval Prolongation during Methadone and Buprenorphine Treatment: a Mortality Assessment Study","volume":"104","author":"Anchersen","year":"2009","journal-title":"Addiction"},{"key":"B2","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1001\/archinternmed.2010.26","article-title":"Substitution of (R,S)-methadone by (R)-methadone: Impact on QTc Interval","volume":"170","author":"Ansermot","year":"2010","journal-title":"Arch. 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