Toxicity of waterborne vortioxetine, a new antidepressant, in non-target aquatic organisms: From wonder to concern drugs?

Vortioxetine is increasing in popularity as a treatment for major depressive disorder and has been detected in wastewater effluent. However, information on the toxicity and environmental risk of vortioxetine in non-target organisms is scarce. Here, embryonic and juvenile zebrafish (Danio rerio) were used to assess the toxicity of vortioxetine (0, 1, 10, 30, 100, 300, and 1000 μg/L) after 120 h and 7 d of exposure, respectively. Vortioxetine induced significant toxicity during embryonic development, including effects on survival, hatching, basal heart rate, spontaneous tail coiling and developmental abnormalities, and inhibited larval locomotor activity at concentrations higher than 30 μg/L. Additionally, vortioxetine evoked anxiolytic-like behavior and caused histopathological changes to multiple organs (gills, heart, liver and intestine) in juvenile zebrafish. Significant increase in 5-HT content was observed in whole zebrafish larvae and juvenile brain tissues from animals treated with 1 or 100 μg/L vortioxetine. Notably, the lowest effective concentrations of vortioxetine for zebrafish were mainly in the range of 10-30 μg/L, which were slightly lower than the vortioxetine therapeutic concentrations. Risk quotients assuming conservative exposure assessments were above one in European countries indicating moderate risk for the behavioral endpoints assessed. We believe that these results highlight the adverse effects of vortioxetine on non-target organisms and that further investigations will be required to provide a higher confidence.