Abstract 11953: Sudden Death Associated With Therapeutic Levels of Methadone: Significance of Drug Interactions

Abstract

Introduction: Methadone for treatment of addiction or chronic pain can be complicated by QT interval prolongation and increased risk of sudden cardiac death (SCD). The concurrent use of additional QT-prolonging medications, such as selective serotonin reuptake inhibitors (SSRIs), may contribute to additional increased risk. We conducted a community-based study to assess the potential role of drug combinations in SCD. Methods: We ascertained residents of Multnomah Co., OR (2002-18) and Ventura Co., CA (2015-21) who suffered SCD and had toxicology reports available. We excluded those under age 18 and those with evidence of recreational drug use or drug overdose. Methadone levels and medications were captured on toxicology reports from the medical examiner. We used logistic regression to compare characteristics and the presence of select medications in those with and without therapeutic levels of methadone at the time of SCD. Results: Of the 789 subjects who met our criteria, the mean (25th-75th percentile) age was 49 (39-59) years, 34% were females, and 85 (11%) had therapeutic levels of methadone. Subjects on methadone were younger, more likely to be female, and had a higher prevalence of SSRIs and benzodiazepines compared to those without methadone (Table). Subjects with methadone had a 3.37 higher odds of SSRI use compared to those without methadone (95% CI: 1.87-6.09). When stratified by mechanistic category, those with methadone had higher odds of QT-prolonging SSRIs [OR (95% CI) = 2.87 (1.35-6.13)] and higher odds of other SSRIs [OR (95% CI) = 3.20 (1.40-7.32)] compared to those without methadone. Combinations of methadone with other selected drug classes did not reach statistical significance. Conclusion: These postmortem findings suggest that the combination of methadone with SSRIs may be associated with additional risk of SCD and warrant further investigation. Drug interactions are a potentially avoidable risk factor for SCD in patients receiving methadone.