AUTHOR=Antoniou Tony , McCormack Daniel , Tadrous Mina , Juurlink David N. , Gomes Tara 

TITLE=The Risk of Ventricular Dysrhythmia or Sudden Death in Patients Receiving Serotonin Reuptake Inhibitors With Methadone: A Population-Based Study

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.861953

DOI=10.3389/fphar.2022.861953

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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’s 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.</p><p><bold>Methods:</bold> 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 <italic>p</italic>-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.</p><p><bold>Results:</bold> 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] 0.90–1.86) and citalopram and escitalopram (adjusted OR 1.26; 95% CI 0.97–1.63) were associated with small increases in the risk methadone-related cardiac toxicity, an assertion supported by the corresponding <italic>p</italic>-value functions.</p><p><bold>Interpretation:</bold> Certain SRIs may be associated with a small increase in cardiac toxicity in methadone-treated patients.</p>