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Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy

A 2018 Update

Patsalos, Philip N. FRCPath, PhD*,†; Spencer, Edgar P. CChem, FRSC, PhD*; Berry, Dave J. FRCPath, PhD*

doi: 10.1097/FTD.0000000000000546
Review Article

Background: Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment. Since 1989, 18 new AEDs have been licensed for clinical use and there are now 27 licensed AEDs in total for the treatment of patients with epilepsy. Furthermore, several AEDs are also used for the management of other medical conditions, for example, pain and bipolar disorder. This has led to an increasingly widespread application of therapeutic drug monitoring (TDM) of AEDs, making AEDs among the most common medications for which TDM is performed. The aim of this review is to provide an overview of the indications for AED TDM, to provide key information for each individual AED in terms of the drug's prescribing indications, key pharmacokinetic characteristics, associated drug–drug pharmacokinetic interactions, and the value and the intricacies of TDM for each AED. The concept of the reference range is discussed as well as practical issues such as choice of sample types (total versus free concentrations in blood versus saliva) and sample collection and processing.

Methods: The present review is based on published articles and searches in PubMed and Google Scholar, last searched in March 2018, in addition to references from relevant articles.

Results: In total, 171 relevant references were identified and used to prepare this review.

Conclusions: TDM provides a pragmatic approach to epilepsy care, in that bespoke dose adjustments are undertaken based on drug concentrations so as to optimize clinical outcome. For the older first-generation AEDs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), much data have accumulated in this regard. However, this is occurring increasingly for the new AEDs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide).

*Epilepsy Society, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire; and

Department of Clinical and Experimental Epilepsy, UCL-Institute of Neurology, Queen Square, London, United Kingdom.

Correspondence: Philip N. Patsalos, FRCPath, PhD, Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, Buckinghamshire SL9 0RJ, United Kingdom (e-mail:

The work undertaken by Professor P. N. Patsalos was performed at UCLH/UCL, who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre funding scheme.

The authors declare no conflict of interest.

This article was prepared at the invitation of the Reviews Editor of Therapeutic Drug Monitoring.

Received March 21, 2018

Accepted May 25, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.