Environmental pollution with psychiatric drugs

Among all contaminants of emerging interest,drugs are the ones that give rise to the greatest concern.Any of the multiple stages of the drug's life cycle(production,consumption and waste management)is a possible entry point to the different environmental matrices.Psychiatric drugs have received special attention because of two reasons.First,their use is increasing.Second,many of them act on phylogenetically highly conserved neuroendocrine systems,so they have the potential to affect many non-target organisms.Currently,wastewater is considered the most important source of drugs to the environment.Furthermore,the currently available wastewater treatment plants are not specifically prepared to remove drugs,so they reach practically all environmental matrices,even tap water.As drugs are designed to produce pharmacological effects at low concentrations,they are capable of producing ecotoxicological effects on microorganisms,flora and fauna,even on human health.It has also been observed that certain antidepressants and antipsychotics can bioaccumulate along the food chain.Drug pollution is a complicated and diffuse problem characterized by scientific uncertainties,a large number of stakeholders with different values and interests,and enormous complexity.Possible solutions consist on acting at source,using medicines more rationally,eco-prescribing or prescribing greener drugs,designing pharmaceuticals that are more readily biodegraded,educating both health professionals and citizens,and improving coordination and collaboration between environmental and healthcare sciences.Besides,end of pipe measures like improving or developing new purification systems(biological,physical,chemical,combination)that eliminate these residues efficiently and at a sustainable cost should be a priority.Here,we describe and discuss the main aspects of drug pollution,highlighting the specific issues of psychiatric drugs.

Genetic variables of the glutamatergic system associated with treatment-resistant depression:A review of the literature

Depression is a common,recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide.Up to 15%-40%of cases do not respond to diverse pharmacological treatments and,thus,can be defined as treatment-resistant depression(TRD).The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment.Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD.Specifically,the N-methyl-D-aspartic acid receptor(NMDAR)andα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor(AMPAR),which are targeted by ketamine and esketamine,are proposed as promising pathways.A literature search was performed to identify studies on the genetics of the glutamatergic system in depression,focused on variables related to NMDARs and AMPARs.Our review highlights GRIN2B,which encodes the NR2B subunit of NMDAR,as a candidate gene in the pathogenesis of TRD.In addition,several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation.These genes encoding glutamatergic receptors could,therefore,be candidate genes for understanding the etiopathogenesis of TRD,as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.