Epilepsy is a disorder characterised by spontaneously occurring recurrent epileptic seizures. It has been estimated that more than 40 million people in the world have epilepsy; the main treatment is with antiepileptic drugs. The aim of treatment is to prevent seizures without causing side effects. The treatment of epilepsy needs to be individualised with respect to both choice of drugs and drug dosage. The latter became apparent during the 1960s when methods for measuring serum concentrations of antiepileptic drugs were developed (Buchtal 1960). The serum concentration of an antiepileptic drug varies markedly between patients given the same dosage; the reason for this is that people differ in their ability to absorb, distribute, metabolise and excrete drugs. These processes are summarised in the term 'pharmacokinetics'. The rate at which these pharmacokinetic processes proceed may be influenced by factors such as the formulation of the drug, concurrent disease, concomitant medication and genetic variables of the individual patient. Thus, many factors contribute to differences in pharmacokinetics and to the individual variability in the serum concentration of a drug. As a consequence of this variability, there may be a wide variation in response to a drug given in a standard dose. Some patients may suffer from poor efficacy whereas others may experience toxic effects unless the dosage is individualised.

Phenytoin was the drug of choice for most seizure types when drug level measurements were introduced in the 1960s and it was found to exhibit particularly complex dose‐dependent pharmacokinetics. As a consequence, it is extremely difficult to predict the effect of a dose change of this drug. Studies carried out in the 1960s and 1970s demonstrated a correlation between the concentration of phenytoin in serum and its therapeutic and toxic effects, thus measuring the serum concentration of phenytoin was soon established as a guide to individualised dosing (Kutt 1968; Kutt 1974; Lund 1974). Since then, drug level monitoring (therapeutic drug monitoring) has been established as a routine aid to optimising treatment with other antiepileptic drugs. The goal of therapeutic drug monitoring is to optimise a patient's clinical outcome by managing the medication regimen, assisted by the measurement of drug concentrations. In general, therapeutic drug monitoring is considered to be of potential value when there is a need for individualised dosing owing to marked inter‐individual differences in drug response when such differences are accounted for by variations in pharmacokinetics, and when it is difficult to monitor drug treatment by direct observation of the therapeutic response and adverse effects, as is sometimes the case in epilepsy. Although most antiepileptic drugs do not share the problems of dose‐dependent kinetics that phenytoin has, many display pronounced inter‐individual variability in pharmacokinetics that suggest the need for individualised dosing. Furthermore, the serum concentration of many antiepileptic drugs can be affected by interactions with other drugs. Therapeutic drug monitoring may facilitate the identification of such interactions.

The concept of therapeutic drug monitoring rests on the assumption that drug concentration correlates better with clinical effects than dose. For some antiepileptic drugs, target ranges of serum concentration have been determined. These are drug concentrations known to be associated with a high probability of seizure control and low risk of toxicity. However, comparatively few studies have been designed specifically to explore the relationship between serum concentrations and effects of antiepileptic drugs, and the documentation in this respect for many of the drugs is scarce (Tomson 2000). Provided there is a distinct concentration‐effect relationship within the individual, therapeutic drug monitoring may be justifiable to control for changes due to drug interactions. This is also possible in the absence of a defined target drug concentration range. It is, however, likely that the value of therapeutic drug monitoring will vary with the different antiepileptic drugs, depending on their pharmacological properties.

The therapeutic drug monitoring service may vary in its methods. Drug concentrations can be measured in specimens other than serum, such as saliva, while analytical methods with varying specificities may also be used. Moreover, there are different ways in which the results of the analysis are presented to the treating physician. This may be just the crude drug concentration or, in some settings, it may be part of a more comprehensive pharmacokinetic service with suggestions for dose adjustments.

Given the heterogeneity in the concept of therapeutic drug monitoring and in the pharmacological characteristics of antiepileptic drugs, it is not surprising that the use of therapeutic drug monitoring varies markedly and that we lack consensus concerning the value of its application in epilepsy (Chadwick 1987). The focus of this review is, therefore, on studies assessing the extent to which therapeutic drug monitoring contributes towards the greater effectiveness of antiepileptic drug treatment.