Abstract
Despite advances in epilepsy therapeutics, some physicians feel uncomfortable with newer antiepileptic drugs (AEDs) due to difficulty in promptly obtaining blood levels to guide medication adjustment, and even when levels for newer AEDs are obtained, many practitioners feel they are not very useful. Lacking confidence in AEDs whose levels that cannot readily or expeditiously be measured, many clinicians share uncertainty about proper use of the newer AEDs and monitoring AED administration. Similarly, some epilepsy patients inflate the importance of AED blood level monitoring, feeling that blood levels falling within traditionally therapeutic ranges are a fail-safe for seizure control, regardless of their compliance or personal behavior aggravating seizure burden, such as poor sleep or use of illicit substances. This review examines the elusive concept of therapeutic AED blood levels and potential uses and abuses of blood level monitoring, reinforcing appropriate uses for blood levels to ensure compliance and adjust for altered AED pharmacokinetics in the context of aging and disease states, pregnancy, or drug interactions.
Highlights
Despite advances in epilepsy therapeutics, some physicians feel uncomfortable with newer antiepileptic drugs (AEDs) due to difficulty in promptly obtaining blood levels to guide medication adjustment, and even when levels for newer AEDs are obtained, many practitioners feel they are not very useful
AED blood levels in a seizure-free patient may be well above or below the standard laboratory therapeutic range, especially when high dose monotherapy is necessary for seizure control where levels may rise well into the “toxic” range to control seizures in intractable patients [7]
A prospective study of AED blood level monitoring with older AEDs found no difference in outcomes of reported seizure control or adverse effects between patients randomized to AED adjustment by clinical practice
Summary
AED blood levels in a seizure-free patient may be well above or below the standard laboratory therapeutic range, especially when high dose monotherapy is necessary for seizure control where levels may rise well into the “toxic” range to control seizures in intractable patients [7]. Lower or “subtherapeutic” blood levels may control seizures in many patients, and raising the dose to “treat the level” and bring it into the therapeutic range does not necessarily improve seizure control [13]. Whether AED blood level monitoring enhances the clinical wisdom of maximally tolerable dosing toward seizure freedom remains unclear [6]. A prospective study of AED blood level monitoring with older AEDs (for which there is most agreement of the validity of established therapeutic ranges) found no difference in outcomes of reported seizure control or adverse effects between patients randomized to AED adjustment by clinical practice,. While blood levels may be desirable for documenting an adequate therapeutic trial and ensuring compliance, for intractable patients pursuing presurgical evaluation, recent prospective observational research has called the practice of maximal tolerated dosing into question. Further research is needed to confirm the “moderate dose approach” to AED therapy and to define what, if any, additional role exists for AED blood level determination
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