Unveiling the Aqueous Environmental Fate of Sertraline as a More Representative Case for Selective Serotonin Reuptake Inhibitors

Abstract The increasing dependence on antidepressants, driven by modern lifestyle pressures, has raised environmental concerns due to their occurrence in surface waters. Here we examine the aqueous environmental fate of sertraline─a widely used and representative selective serotonin reuptake inhibitor (SSRI)─in comparison with paroxetine, fluoxetine, and citalopram. Combining state-of-the-art quantum-chemical calculations and machine-learning tools with controlled photochemical experiments, we elucidate degradation pathways, toxicity/genotoxicity and ecological implications. We identified hydroxyl radicals, singlet oxygen, and chromophoric dissolved organic matter as the key oxidants governing transformation in natural waters and mapped the most susceptible sites on the sertraline scaffold, with halogenated alkyl motifs emerging as primary targets. Although sertraline was estimated to be more toxic and genotoxic than its analogues, its transformation products are predicted to be substantially less harmful. These results position sertraline as a robust case study for mitigation across the SSRI class, guiding environmentally responsible management of antidepressants.