Reappraisal of polytherapy in epilepsy: a critical review of drug load and adverse effects

Epilepsia
Charles L P DeckersW O Renier

Abstract

We reviewed the literature to determine whether an analysis of published data could clarify the relationship between antiepileptic drug (AED) polytherapy and adverse affects (AE). We highlight the problems encountered. We made a Medline-search for articles published between 1974 and 1994 reporting the number of AE and doses or serum levels of every AED, per patient or treatment group, and used the PDD/DDD ratio to calculate AED load per patient from doses or the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/DDD is the sum of ratios of the actual prescribed daily doses divided by the published average therapeutic dose of each drug. The OSL/AToxL is the sum of each observed serum level divided by its average toxic level. We retrieved 118 trial reports. Most had to be excluded because of incomplete reporting of concomitant medication or AE. The data of the 15 articles selected for further analysis indicate a relationship between drug load and number of AE. We noted no relationship between the number of AEDs administered and AE. In add-on studies, the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of...Continue Reading

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Citations

Feb 25, 2005·Journal of Neurology·Martin J Brodie
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