Time-Dependent Intrinsic Correlation Analysis Reveals Positive Relationship between Drug Types in Wastewater: Antidepressants vs Illicit Drugs and Analgesics vs Antibiotics/Antivirals

The connection between mental health and illicit substance use disorder is intricate and poorly understood but may potentially be unraveled by examining residues of antidepressants and illicit drugs through wastewater-based epidemiology (WBE). In this study, we assessed time-dependent intrinsic correlations (TDIC) between the concentrations of antidepressants and illicit drugs and their metabolites in untreated sewage samples during three sampling campaigns, from September 2022 to May 2024. Notable positive correlations (+medium in 2022; +weak in 2023; +medium in 2024) were observed between illicit drugs (e.g., methamphetamine, cocaine, and its benzoylecgonine metabolite) and bupropion (an antidepressant). For other psychoactive drugs examined (citalopram, venlafaxine, and its metabolite desvenlafaxine), +medium correlations were observed with illicit drugs in the 2023 and 2024 sampling campaigns. This is the first time WBE demonstrates the interconnection between prescription psychoactive drugs, such as antidepressants, and illicit drugs, underscoring TDIC’s strength in extracting information from complementary data. We applied similar data analytics using residues of antivirals and antibiotics in untreated sewage and their correlation with acetaminophen; the expected results were obtained. TDIC between acetaminophen and antibiotics showed a strong correlation during the whole sampling event, supporting the applicability of TDIC in WBE research.