Critical insights into the potential risks of antipsychotic drugs to fish, including through effects on behaviour

Antipsychotic drugs (APDs) are a diverse class of neuroactive pharmaceuticals increasingly detected in surface and ground waters globally. Some APDs are classified as posing a high environmental risk, due, in part, to their tendency to bioaccumulate in wildlife, including fish. Additional risk drivers for APDs relate to their behavioural effects, potentially impacting fitness outcomes. However, standard ecotoxicological tests used in environmental risk assessment (ERA) do not currently account for these mechanisms. In this review, we critically appraise the environmental risks of APDs to fish. We begin by reading-across from human and mammalian effects data to standard ecotoxicological effects endpoints in fish. We then explore the wide range of behaviours suitable for ecotoxicological assessment of APDs (and other neuroactive) pharmaceuticals, principally through laboratory studies with zebrafish, and assess the potential for using these behavioural phenotypes to predict adverse individual- and population-level outcomes in wild fish, taking into account phenotypic plasticity. Next, we illustrate the advantages and challenges of measuring and applying behavioural endpoints for fish, including within current regulatory risk assessments. In our final analysis, the implications of relying on apical endpoints for ERA of neuroactive drugs (including APDs) are assessed and recommendations provided for the development of a more refined and tailored mechanistic approach, which would enable more robust assessment of their environmental risk(s).