ReviewA review of antiepileptic drugs: Part 1 occurrence, fate in aquatic environments and removal during different treatment technologies
Graphical abstract
Introduction
Epilepsy is the second most common neurological disease after stroke, affecting almost 70 million people worldwide (Ngugi et al., 2010). This disease is characterized by recurrent seizures, as well as loss of consciousness and control of bowel function.
Currently, there are more than 30 AEDs approved for the treatment of seizures. However, in recent years, more and more people are using them for other indications such as: migraine, chronic neuropathic pain, and mood disorders (Druschky et al., 2018; Liu et al.,2017). Consequently, a new group of patients are being exposed to this pharmaceutical group, which means that prescriptions and consumption of these drugs are increasing worldwide. For example, from 1999 to 2009 in U.S., the use of levetiracetam increase from 5.1% to 32%, while the use oxcarbazepine increased from 1.3% to 19.1% (Liu et al., 2017). In addition, in Norway, Baftiu et al. (2016) pointed out that the use of AEDs in non-epileptic disorders is increasing and represented 53% in the year 2012.
Due to their increasing consumption and their barely degradation in WWTPs, AEDs are widely distributed in surface water around the world. Carbamazepine, gabapentin, lamotrigine, and primidone have been the most frequently AEDs detected in the world's rivers and lakes. However, other AEDs such as topiramate, phenytoin and primidone have been also found at much lower concentrations.
In light of these considerations, the central aim of this study was to comprehensively investigate the occurrence, distribution and fate of AEDs on the different aquatic systems. Finally, we also investigated and compared the current treatment technologies used to remove AEDs from wastewater.
Section snippets
Worldwide consumption of AEDs
In recent decades there has been a significant increase in the consumption of AEDs, as is shown in Table 1. This may be due to the extensive usage of these drugs to treat other conditions, such as chronic pain, migraine, bipolar disorder, and depression (Druschky et al., 2018; Parikh and Silberstein, 2019). Rogawski and Löscher, 2004, for instance demonstrated that in 2003 about half of the prescriptions for AEDs in the US were for conditions other than epilepsy. Furthermore, in Norway, from
Occurrence and spatial distribution of AEDs in water systems
In order to predict, regulate and understand the risks that pharmaceutical products represent to the environment, it is important to determine their fate and abundance once they enter into the environment.
AEDs are mainly introduced into the environment thought the discharge of effluents from municipal wastewater treatment plants and/or hospital effluents. This is due to AEDs cannot be completely eliminated using the current processes of WWTPs. For example, several studies have suggested that
Transport and fate of AEDs in solid matrices
Sediments originate from the erosion of minerals and soil, and just like water, are a very dynamic part of river systems (Babić and Mutavdžić Pavlović, 2013). These are transported downstream to the coast, where they are discharged into seas and oceans. Furthermore, in lowland areas where river flow velocity decreases, sediments are deposited along the banks and beds.
Once in the environment, AEDs are distributed in the water phase, as suspended particles or in the sediments, depending on their
Methods of quantification of AEDs
The method of choice to monitor the fate of CBZ (log KOW of 2.4) and its metabolites in trace levels is liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Here, it is important to emphasize that samples must be preconcentrated using solid phase extraction (SPE), in order to enhance the detection limit and reduces matrix effects (Bahlmann et al., 2014).
The separation of AEDs has been carried out with reversed-phase chromatography using high-performance liquid chromatography
Removal of AEDs from WWTPs
Since AEDs are ubiquitously distributed in worldwide water bodies, it is suggested that wastewater treatment processes are not effective in eliminating these drugs from effluents. In addition, several studies have demonstrated that these drugs may result harmful to aquatic organisms at environmentally relevant concentrations. Thus, new alternatives for the removal of these drugs from effluents should be urgently investigated.
The following section briefly discuss the removal rates achieved under
Conclusions and perspectives
A solid understanding for the occurrence and fate in aquatic environments for most of the pharmaceutical products has been gained in the last decade. However, it is necessary to expand this knowledge on other pharmaceutical groups, such as AEDs.
AEDs have been found in several water bodies around the world, and carbamazepine has been the most frequently anticonvulsant detected in most of the studies. However, in the last decade, the use of AEDs has changed, showing an important increase in the
Declaration of competing interest
The authors declare that they have no conflict of interest.
References (169)
- et al.
Algae-mediated removal of selected pharmaceutical and personal care products (PPCPs) from Lake Mead water
Sci. Total Environ.
(2017) - et al.
Utilization of antiepileptic drugs in Israel
Epilepsy and Behavior
(2016) - et al.
Occurrence, distribution and environmental risk of pharmaceutically active compounds (PhACs) in coastal and ocean waters from the Gulf of Cadiz (SW Spain)
Sci. Total Environ.
(2018) - et al.
Biodegradation of pharmaceuticals in hospital wastewater by staged Moving Bed Biofilm Reactors (MBBR).
Water Res.
(2015) - et al.
Organic micropollutants in the surface riverine sediment along the lower stretch of the transboundary river Ganga: occurrences, sources and ecological risk assessment
Environ. Pollut.
(2019) - et al.
Micropollutant removal in an algal treatment system fed with source separated wastewater streams
J. Hazard. Mater.
(2016) - et al.
Removal of pharmaceuticals in microcosm constructed wetlands using Typha spp. and LECA
Bioresour. Technol.
(2010) - et al.
Pharmaceuticals in freshwater aquatic environments: A comparison of the African and European challenge
Sci. Total Environ.
(2019) - et al.
Organic contaminants in African aquatic systems: Current knowledge, health risks, and future research directions
Sci. Total Environ.
(2018) - et al.
Photocatalytic degradation of carbamazepine and three derivatives using TiO2 and ZnO: Effect of pH, ionic strength, and natural organic matter
Sci. Total Environ.
(2014)
Trends in the use of antiepileptic drugs in Taiwan from 2003 to 2007: A Population-Based National Health Insurance study
Epilepsy Res.
Utilization of antiepileptic drugs in Hong Kong children
Pediatr. Neurol.
Trends in Antiepileptic Drug Use in Children and Adolescents With Epilepsy
Pediatr. Neurol.
Occurrence and health risk assessment of pharmaceutical and personal care products (PPCPs) in tap water of Shanghai
Ecotoxicol. Environ. Saf.
Occurrence of pharmaceutical compounds in wastewater and sludge from wastewater treatment plants: removal and ecotoxicological impact of wastewater discharges and sludge disposal
J. Hazard. Mater.
The occurrence of emerging trace organic chemicals in wastewater effluents in Saudi Arabia
Sci. Total Environ.
Occurrence and spatial distribution of 158 pharmaceuticals, drugs of abuse and related metabolites in offshore seawater
Sci. Total Environ.
Pharmaceuticals, personal care products, food additive and pesticides in surface waters from three Australian east coast estuaries (Sydney, Yarra and Brisbane)
Mar. Pollut. Bull.
Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems
Philos. Trans. R. Soc. B Biol. Sci.
Fate and transport of carbamazepine in soil aquifer treatment (SAT) infiltration basin soils
Chemosphere.
Laboratory- and full-scale studies on the removal of pharmaceuticals in an aerated constructed wetland: effects of aeration and hydraulic retention time on the removal efficiency and assessment of the aquatic risk
Water Sci. Technol.
Antidepressants in urban wastewater treatment plant: occurrence, removal and risk assessment
Glob. Nest J.
Analysis of PhACs in solid environmental samples (soil, sediment, and sludge)
Changes in utilisation of antiepileptic drugs in epilepsy and non-epilepsy disorders—a pharmacoepidemiological study and clinical implications
Eur. J. Clin. Pharmacol.
Carbamazepine and its metabolites in wastewater: analytical pitfalls and occurrence in Germany and Portugal
Water Res.
Occurrence, distribution, and seasonality of emerging contaminants in urban watersheds
Chemosphere.
Carbamazepine and other anti-epileptic drugs in the aquatic environment
Czas. Tech. Środowisko.
Biodegradation of persistent polar pollutants in wastewater: comparison of an optimised lab-scale membrane bioreactor and activated sludge treatment
Water Res.
Pharmaceutical residues are widespread in Baltic Sea coastal and offshore waters — screening for pharmaceuticals and modelling of environmental concentrations of carbamazepine
Sci. Total Environ.
Occurrence and fate of amisulpride, sulpiride, and lamotrigine in municipal wastewater treatment plants with biological treatment and ozonation
J. Hazard. Mater.
Highly sensitive determination of 68 psychoactive pharmaceuticals, illicit drugs, and related human metabolites in wastewater by liquid chromatography-tandem mass spectrometry
Anal. Bioanal. Chem.
Investigation and risk evaluation of the occurrence of carbamazepine, oxcarbazepine, their human metabolites and transformation products in the urban water cycle
Environ. Pollut.
Pharmaceutical concentration variability at sewage treatment plant outlets dominated by hydrology and other factors
Environ. Pollut.
Temporal and spatial variation in pharmaceutical concentrations in an urban river system
Water Res.
Determination of selected pharmaceuticals in tap water and drinking water treatment plant by high-performance liquid chromatography-triple quadrupole mass spectrometer in Beijing, China
Environ. Sci. Pollut. Res.
Occurrence, temporal evolution and risk assessment of pharmaceutically active compounds in Doñana Park (Spain)
J. Hazard. Mater.
Removal of micropollutants through a biological wastewater treatment plant in a subtropical climate, Queensland-Australia
J. Environ. Heal. Sci. Eng.
Diclofenac and carbamazepine removal from domestic wastewater using a constructed wetland-solar photo-Fenton coupled system
Ecol. Eng.
Inputs, source apportionment, and transboundary transport of pesticides and other polar organic contaminants along the lower Red River, Manitoba, Canada
Sci. Total Environ.
Graphene oxide/titania photocatalytic ozonation of primidone in a visible LED photoreactor
J. Hazard. Mater.
Distribution and accumulation of endocrine-disrupting chemicals and pharmaceuticals in wastewater irrigated soils in Hebei, China
Environ. Pollut.
Removals of pharmaceuticals in municipal wastewater using a staged anaerobic fluidized membrane bioreactor
Int. Biodeterior. Biodegrad.
Occurrence, removal and environmental risk assessment of pharmaceuticals and personal care products in rural wastewater treatment wetlands
Sci. Total Environ.
Trends in Antiepileptic Drug Prescriptions for Childhood Epilepsy at a Tertiary Children’s Hospital in Korea, 2001–2012
Pediatr. Drugs
Triclosan, carbamazepine and caffeine removal by activated sludge system focusing on membrane bioreactor
Process. Saf. Environ. Prot.
Pharmaceutical pollution of water resources in Nakivubo wetlands and Lake Victoria, Kampala, Uganda
Sci. Total Environ.
Occurrence of contaminants of emerging concern in aquatic ecosystems utilized by Minnesota tribal communities
Sci. Total Environ.
Removal of emerging contaminants from municipal wastewater with an integrated membrane system, MBR-RO
J. Hazard. Mater.
Fate of trace organics in a wastewater effluent dependent stream
Sci. Total Environ.
Occurrence and discharge of pharmaceuticals and personal care products in dewatered sludge from WWTPs in Beijing and Shenzhen
Emerg. Contam.
Cited by (19)
Theoretical insights into the degradation mechanisms, kinetics and eco-toxicity of oxcarbazepine initiated by OH radicals in aqueous environments
2023, Journal of Environmental Sciences (China)Citation Excerpt :Oxcarbazepine (10,11-dihidro-10-oxo-5H-dibenzo-[b,f]azepine-5-carboxamide, OXC), as a 10-keto analogue of carbamazepine (CBZ), is more widely applied to the treatment of epilepsy due to its excellent tolerability and slight side effect (Reinikainen et al., 1987; Wang et al., 2018). OXC has been extensively used in over 50 countries, and its popularity is increasing every year (Cardoso Vera et al., 2021). For example, the annual consumption increased sharply from 2900 to 6700 kg between 2002 and 2005 in France, and the use of OXC in Germany reached 12,800 kg in 2012 (Bahlmann et al., 2014).
Removal of pharmaceutical compounds from real urban wastewater by a continuous bio-electrochemical process at pilot scale
2023, Journal of Environmental Chemical EngineeringEffects of common antiepileptic drugs on teleost fishes
2023, Science of the Total EnvironmentNeuroactive pharmaceuticals in estuaries: Occurrence and tissue-specific bioaccumulation in multiple fish species
2023, Environmental PollutionCitation Excerpt :It was found in every sample from the Douro, Tejo and Mira estuaries, and 86% of samples in the Sado estuary, at concentrations ranging from 0.1 to 61 ng/L. Carbamazepine is a commonly prescribed antiepileptic worldwide, known to be able to resist wastewater treatment at low concentrations and is the most frequently detected antiepileptic in wastewaters and in the environment worldwide (Adeleye et al., 2022; aus der Beek et al., 2016; Cardoso-Vera et al., 2021; Zhang et al., 2008). Hence, in estuarine and coastal waters carbamazepine has been found to reach maximum concentrations of thousands of ng/L (e.g. McEneff et al., 2014), and many studies frequently report 100% detection in surface waters (Cardoso-Vera et al., 2021). Other antiepileptics analysed included clonazepam and topiramate, which were less frequently detected (up to 44 and 17%, respectively) and at concentrations up to 4.9 and 15 ng/L, respectively.
Impacts of wastewater effluents and seasonal trends on levels of antipsychotic pharmaceuticals in water and sediments from two cold-region rivers
2022, Science of the Total Environment