Safety aspects of antiepileptic drugs-a population-based study of adverse effects relative to changes in utilisation.

PURPOSE: Antiepileptic drugs (AEDs) are increasingly used, and knowledge about adverse effects is scarce based on clinical studies. The purpose of the present study was to characterise adverse effects reports of AEDs in Norway relative to changes in utilisation in various indications from population-based data to elucidate important safety aspects of use of AEDs.

METHODS: Aggregated data of adverse effects reported for AEDs in Norway from the EudraVigilance-database (2004-2013) in addition to indication-specific use of AEDs during 2004-2015 from the Norwegian Prescription Database were used.

RESULTS: The use of AEDs increased twofold the last decade due to use in psychiatry and neuropathic pain: lamotrigine, pregabalin, gabapentin, valproate, and carbamazepine. There were 1593 adverse effects reported (403 Individual Case Safety Reports, 2/3 women), 0-95 years (mean 46). Most adverse effects were reported for pregabalin (593), carbamazepine (265), lamotrigine (206), gabapentin (144), and valproate (119), where pregabalin had by far the highest reports in relation to the number of users. The most frequently reported adverse drug effects included rash, dizziness, cross-sensitivity reactions, and pyrexia. Overall, nervous system disorders constitute the largest organ class with the majority of the reports. Reporting of fatal outcomes is mandatory, and sudden unexplained death in epilepsy (SUDEP) was reported in 34 occasions.

CONCLUSIONS: This study demonstrates that most adverse effects reported concerned AEDs increasingly used in non-epilepsy indications: neuropathic pain (pregabalin, gabapentin, carbamazepine) and psychiatry (lamotrigine, valproate, carbamazepine). Pregabalin had the highest prevalence of adverse effects reported in relation to number of users. This elucidates an important part of pharmacovigilance for improved safety and considerations in clinical practice.