OBJECTIVES: Antiepileptic drugs (AEDs) are the cornerstone in epilepsy treatment, and are widely used in the management of bipolar disorder, schizophrenia, neuropathic pain and migraine. However, their potential risk of severe cutaneous adverse reactions (SCARs), particularly among aromatic AEDs, remain significant concerns. This study aimed to investigate the 10-year trend in AEDs use and AEDs-related SCARs in Taiwan.

METHODS: A nationwide, cross-sectional study was performed using Taiwan’s National Health Insurance Research Database. Nine mostly prescribed AEDs were defined as study drugs and classified as aromatic (carbamazepine, phenytoin, phenobarbital, oxcarbazepine, and lamotrigine) or non-aromatic (valproate, gabapentin, topiramate, and levetiracetam). New users of AEDs received their first AEDs prescriptions between 2005 and 2014 were included, and those experienced SCAR-related admissions within 3 months after the first prescriptions were identified using previously validated ICD-9-CM codes. Annual number of AEDs new users and incidence rates of AEDs-related SCARs were assessed.

RESULTS: During the 10-year period, new users of aromatic AEDs decreased 63.6%, while new users of non-aromatic AEDs increased 77.2%. Among 2,081 cases of AEDs-related SCARs identified between 2005 and 2014, aromatic AEDs accounted for 82.1% of the cases. Nevertheless, aromatic AEDs-related SCARs decreased over time (246 cases in 2005 vs. 91 cases in 2014). Incidence rates of SCARs varied across AEDs, and the highest was observed among new users of lamotrigine (16.47 per 1000 person years in 2014), followed by phenytoin (16.22), carbamazepine (9.21), phenobarbital (5.68), and oxcarbazepine (4.13). New users of non-aromatic AEDs had lower incidence rates of SCARs (levetiracetam 3.22, gabapentin 2.10, valproate 1.61, and topiramate 1.55).

CONCLUSIONS: Aromatic AEDs had higher incidence rates of SCARs and accounted for the majority of AEDs-related SCARs. However, new users of aromatic AEDs decreased over the past 10 years, and there was simultaneous decrease in the number of aromatic AEDs-related SCAR cases.