Review
A review of antiepileptic drugs: Part 1 occurrence, fate in aquatic environments and removal during different treatment technologies

https://doi.org/10.1016/j.scitotenv.2021.145487Get rights and content

Highlights

  • The use of antiepileptic drugs in non-epileptic disorders has steadily increased.

  • Antiepileptic drugs are ubiquitously distributed in worldwide waterbodies.

  • Photodegradation processes can improve the biodegradability of antiepileptic drugs.

  • Little or no information is known about the antiepileptic drugs byproducts.

Abstract

Antiepileptic drugs (AEDs) are the main treatment for people with epilepsy. However, in recent years, more and more people are using them for other indications such as: migraine, chronic neuropathic pain, and mood disorders. Consequently, the prescriptions and consumption of these drugs are increasing worldwide. In WWTPs, AEDs can resist degradation processes, such as photodegradation, chemical degradation and/or biodegradation. Until now, only constructed wetlands and photocatalysis have shown good removal rates of AEDs from wastewater. However, their effectiveness depends on the specific conditions used during the treatment. Since the consumption of AEDs has increased in the last decade and their degradation in WWTPs is poor, these drugs have been largely introduced into the environment through the discharge of municipal and/or hospital effluents. Once in the environment, AEDs are distributed in the water phase, as suspended particles or in the sediments, suggesting that these drugs have a high potential for groundwater contamination. In this first part of the AEDs review is designed to fill out the current knowledge gap about the occurrence, fate and removal of these drugs in the aquatic environment. This is a review that emphasizes the characteristics of AEDs as emerging contaminants.

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.

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