A Double Challenge for Fish: The Combined Stress of Warming and Pharmaceuticals in Aquatic Systems

Aquatic ecosystems are increasingly threatened by multiple anthropogenic stressors, notably climate change and pollution by pharmaceuticals. Global warming is predicted to raise water temperatures by 2-5 °C by the end of the century. As ectotherms, fish are particularly vulnerable due to limited thermal tolerance and temperature-dependent physiology. Pharmaceuticals are introduced into aquatic systems at concentrations ranging from ng·L^-1 to µg·L^-1, including widely prescribed classes such as antibiotics, hormones, analgesics, antifungals, and neuropsychiatric drugs. This narrative review synthesizes experimental evidence on the interactive effects of warming and pharmaceutical exposure in fish. Thirty-nine peer-reviewed studies published since 2005 were analyzed. The findings indicate that higher temperatures often exacerbate pharmaceutical-induced toxicity, altering oxidative stress, metabolism, reproduction, and behavior. Antibiotic-focused studies showed temperature-dependent acceleration of absorption, distribution, metabolism, and excretion, with shorter half-lives and reduced tissue persistence at higher temperatures. Estrogenic hormones and antifungals have been shown to interact with thermal regimes, disrupting reproductive physiology and skewing sex ratios, particularly in species exhibiting temperature-dependent sex determination. Neuropsychiatric drugs exhibited altered uptake and metabolism under warming conditions, resulting in increased brain bioaccumulation and behavioral alterations affecting ecological fitness. Analgesics and anti-inflammatories remain understudied despite their widespread use, with evidence suggesting synergistic effects on oxidative stress at elevated temperatures. Significant research gaps persist regarding chronic exposures, early developmental stages, ecologically relevant temperature scenarios, and underrepresented or absent drug classes, such as hypolipidemic drugs. Ultimately, broader and integrated approaches are needed to better understand and predict the ecological risks of pharmaceutical pollution in a warming world.