The substances driving the overdose epidemic in the United States have changed over time. Since 2013, fentanyl-analogues have become the primary opioids driving the epidemic. Recently, polysubstance related deaths have come to the forefront of the epidemic. Therefore, we explored trends in polysubstance involvement in overdose fatalities in Maryland between 2003 and 2019.
We used records for the Maryland Office of the Chief Medical Examiner between 2003 and 2019. First, we assessed trends in the number of drugs (1, 2, 3+) involved in overdose fatalities over time. Then, we assessed linear and quadratic trends in nine substance categories using logistic regression.
Overtime, the proportion of overdose deaths involving one (ß=-0.28, p < 0.001) or two (ß=-0.14, p < 0.001) drugs decreased, while deaths involving three or more drugs increased (ß = 0.31, p < 0.001). The involvement of most drugs decreased over the study period. Only cocaine (linear ß=-0.08, p < 0.001; quadratic ß = 0.29, p < 0.001) and fentanyl (linear ß = 1.67, p < 0.001; quadratic ß = 0.75, p < 0.0001) showed significant increases over time. Post hoc analyses showed that cocaine involvement only increased in the presence of fentanyl (linear ß = 1.41, p < 0.001; quadratic ß = 0.70, p < 0.001) and decreased when fentanyl was not present (linear ß=-0.81, p < 0.001; quadratic ß=-0.31, p < 0.001).
Polysubstance involvement in overdose fatalities has become more common over time in Maryland. Most individual substances became less common over time, while cocaine and fentanyl involvement increased. Unintentional fentanyl consumption through contaminated cocaine may be an increasingly important driver of deaths in Maryland, indicating the importance of implementing widespread harm reduction programs, especially drug checking.

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