title: Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring.
abstract: This review focuses on the evolution of approaches to dosing of antiepileptic drugs (AEDs) in clinical practice through history. There has been a shift in the view of treatment of epilepsy, from "one dose fits all patients" in the early days to individualisation of treatment. Over the past 50 years, our knowledge of pharmacological variability of AEDs has markedly increased through implementation of therapeutic drug monitoring (TDM). The use of TDM has demonstrated extensive pharmacokinetic variability for AEDs and a need to individualise the treatment for an optimal outcome. Factors that contribute to pharmacokinetic variability include external factors (including food and comedication), physiological factors (gender, age, and pregnancy), pathological conditions (organ dysfunction), and genetic factors (polymorphisms in metabolising enzymes). Patient groups of children, pregnant women, and the elderly, in whom the most extensive pharmacokinetic changes occur, need special attention and close follow-up of treatment. Patients with complicated and changing combination treatments are also vulnerable. Therapeutic drug monitoring may be particularly helpful in such situations. There are also challenges regarding the use and misuse of therapeutic drug monitoring, such as the use of drug monitoring without a clear indication, misinterpretation of the reference range, and erroneous sampling times.
authors.affiliation: Programme for Pharmacy, Dept. of Life Sciences and Health, Oslo and Akershus University College of Applied Sciences, Oslo, Norway, The National Center for Epilepsy, Sandvika, Oslo University Hospital, Norway, Dept. of Pharmacology, Oslo University Hospital, Norway.
authors.forename: Cecilie Johannessen
authors.initials: CJ
authors.lastname: Landmark
authors.affiliation: The National Center for Epilepsy, Sandvika, Oslo University Hospital, Norway, Dept. of Pharmacology, Oslo University Hospital, Norway.
authors.forename: Svein I
authors.initials: SI
authors.lastname: Johannessen
authors.affiliation: Dept. of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Tomson
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans
chemical_list: D000927:Anticonvulsants
keywords: antiepileptic drugs; dosing strategies; efficacy; individualisation; lessons from history; pharmacokinetic variability; therapeutic drug monitoring; tolerability