Wastewater-based epidemiology (WBE) offers a promising approach by providing objective data on antipsychotic drug consumption within a population that can be used to monitor abuse, misuse, and regional prescription patterns. However, accurate estimations depend on knowing the stability of drug biomarkers. This study provides a comprehensive analysis of the stability of 11 antipsychotic biomarkers (parent drugs and their metabolites) in influent wastewater, using a series of experiments mimicking in-sewer transport (in-sewer setup and deconjugation) and in-sample stability (benchtop, frozen cartridge, long-term sample storage, and freeze-thaw). In-sample stability experiments are exposed to various conditions (i.e., filtration, acidification) commonly used for storage. The results reveal compound-specific stability profiles, with quetiapine showing notable high stability across most experiments. In contrast, N-desmethylolanzapine and dehydroaripiprazole demonstrated rapid degradation. Acidification before storage led to significant degradation of some compounds, decreasing the accuracy of WBE consumption estimates and rendering it unsuitable as a sample storage method. Overall, the study found that compound-specific degradation patterns underscore the necessity for tailored analytical approaches when using WBE to monitor antipsychotic drug use. Future research should focus on bioreactor studies mimicking in-sewer conditions and the application of correction factors to enhance the accuracy of consumption estimates, facilitating more reliable public health surveillance through WBE.