Understanding Target-Specific Effects of Antidepressant Drug Pollution on Molluscs: A Systematic Review Report

Antidepressant drugs (ADDs) are one of the most widely prescribed pharmaceuticals globally and are widely detected in the environment. They are designed to target monoamine neurotransmission-a highly conserved pathway between humans and animal species. Monoamines are particularly involved in the regulation of a wide array of key biological functions in molluscs, an ecologically important group of animals. Despite this, the target-specific effects of environmental concentrations of different classes of ADDs in molluscs remain poorly understood. The present study seeks to understand the target-specific effects of environmental concentrations of different classes of ADDs in molluscs through a systematic review of the literature. This study, following our published systematic review protocol, analyzed 51 studies after deduplication and screening of 1156 identified records. Included studies reported on a range of outcomes, including reproductive, (loco)motor, developmental, behavioral, immuno-modulating and neurophysiological effects. Data synthesis was performed with a harvest plot of exposures, effect direction and risk of bias. We found evidence (weak to moderate) for (i) immunosuppression, resulting from tissue serotonin level elevation, (ii) larval development impairment, and (iii) acetylcholinesterase inhibition, at environmental concentrations of ADDs. Most study outcomes, in addition to data-deficient outcomes, were inconclusive due largely to methodological limitations such as the use of wild-derived species with minimal or no acclimation (65.38% of included studies), lack of proper controls and replicates, and unrealistic exposures, affecting the reliability of existing data. Although the observed effects-particularly immunosuppressive ones-provide critical insight into the ecological risks posed by ADDs, their impacts at environmentally relevant concentrations remain poorly characterized for most endpoints. Given the ecological importance of molluscs, further studies addressing the identified methodological and research gaps are urgently needed to better characterize the hazards posed by environmental concentrations of ADDs.