Adverse events with use of antiepileptic drugs: a prescription and event symmetry analysis†

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To assess adverse events with use of antiepileptic drugs (AEDs) by the method of sequence symmetry analysis.


We used data from two population-based sources in Funen County, Denmark (population 2006: 479 000); prescription data from Odense University Pharmacoepidemiological Database (OPED) for the period of 1 August 1990–31 December 2006, and diagnoses from the County Hospital register for the period of 1994–2006 to perform sequence symmetry analysis. The method assesses the distribution of disease entities and prescription of other drugs (ODs), before and after initiation of AED treatment, as asymmetry in these distributions may indicate adverse events of AED use. Crude and adjusted sequence ratios (ASRs) with 95% confidence intervals (CI) were calculated.


We identified 24 882 incident AED users during the study period. Analysis with predefined drugs and diagnoses detected known AED adverse events of unspecific (constipation, nausea) and specific character (hyponatraemia, osteoporosis). Unanticipated signals from analysis without any preselection of drugs and diagnoses were the association of topiramate with dopaminergic agents (ASR 10.4; 95%CI 1.5–448), of gabapentin with glaucoma (ASR 8.0; 95%CI 1.1–355) and of valproic acid with hypothyroidism (ASR 8.0; 95%CI 1.1–355).


Few unsuspected adverse AED effects were recognized in our study. Sequence symmetry analysis is a feasible method of monitoring for adverse AED effects. Copyright © 2009 John Wiley & Sons, Ltd.

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