Effects of fluoxetine on fish: What do we know and where should we focus our efforts in the future?

Fluoxetine is one of the most studied and detected selective serotonin reuptake inhibitors in the aquatic environment, found at concentrations ranging from ng/L to mu g/L. Its presence in this environment can induce effects on aquatic or-ganisms that may compromise their fitness. Several experimental studies have demonstrated that fluoxetine can in-duce neurotoxicity, genetic and biochemical changes, and cause behavioral dysfunction in a wide range of fish species. However, contradictory results can be found. There is thus the need for a comprehensive review of the current state of knowledge on the effects of fluoxetine on fish at different levels of biological organization, highlighting inclu-sive patterns and discussing the potential causes for the contradictory results, that can be found in the available liter-ature. This review also aims to explore and identify the main gaps in knowledge and areas for future research. We conclude that environmentally relevant concentrations of fluoxetine (e.g., from 0.00345 mu g/L) produced adverse ef-fects and often this concentration range is not addressed in conventional environmental risk assessment strategies. Its environmental persistence and ionizable properties reinforce the need for standardized testing with representative aquatic models, targeting endpoints sensitive to the specific mode of action of fluoxetine, in order to assess and rank its actual environmental risk to aquatic ecosystems.