Ecotoxicological implications of increased antidepressant concentrations in the Laurentian Great Lakes Basin, 2018–2023

Antidepressants are only partially metabolized and then eliminated in urine and feces. Since waste water treatment plants are not designed to remove pharmaceuticals, antidepressants and their metabolites eventually reach the environment. Antidepressants are among the most prescribed drugs in the world, and their prescription rates increased dramatically following the onset of the COVID-19 pandemic. Our aim was to compare their measured environmental concentrations (MECs) in surface water in the three years before and the three years after the pandemic onset. Nearly 1300 samples were collected from 67 sites in the Laurentian Great Lakes Basin, from streams and rivers. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology to measure the MECs of 7 of the most frequently used antidepressants and 3 of their metabolites. Canadian antidepressant use data was also collected via the IQVIA MIDAS® database of estimated sales data for pharmaceutical drugs (2018-2021). We found that the median MECs for 9 of the 10 substances increased between 1.5- and 7.2-fold (p < 0.05). The greatest median increases corresponded to fluvoxamine (4.8-fold) and 10-hydroxyamitriptyline (4.7-fold). Increases were concurrent with rising use rates post-COVID-onset. The highest concentrations corresponded to the metabolite O-desmethylvenlafaxine (3113.98 ng L^-1) and its parent drug venlafaxine (699.59 ng L^-1) in 2022. We collected and analyzed antidepressant surface water and ecotoxicological data to provide a comprehensive review to contextualize the LC-MS/MS data. We compared maximal MECs to ecotoxicological reference values and theorize a possible ecotoxicological impact when considering the overlap of maximal levels with ecotoxicological reference values cited in the scientific literature. We offer recommendations for next steps.