Epilepsy Adverse Drug Reactions Study

Study participants were patients diagnosed with epilepsy by the Department of Neurology in Ningxia Medical University General Hospital. The inclusion criteria were as follows: ① Ningxia resident with no history of marriages with other ethnic groups for more than three generations; ② Clear indications for AEDs treatment; ③ Have not been administered oral AEDs, and potential adverse drug reactions declared in patients or their guardians, after which signed informed consents were obtained; and ④ The initial dose and increasing dose of AEDs determined according to the “Pharmacopeia of People's Republic of China” (2010 edition). The exclusion criteria were as follows: ① Having a history of alcohol-related epilepsy; ② Having a treatable cause (such as metabolic disorders, poisoning, and infection); ③ With progressive brain or central nervous system diseases, such as encephalitis, tumors, or degenerative diseases; ④ Suffering from other diseases and the emergence of allergy during the follow-up period; and ⑤ Having to discontinue or substitute medications and not completing 12 weeks of prescribed oral AEDs.
Four hundred and fifteen patients were followed up bi-weekly for 12 weeks after initiating oral AEDs. The initial dosage of PHT, LTG, CBZ, and valproate (VPA) was 200, 500, 12.5, 100 mg/d, and 5 mg/kg/d, respectively. They were examined for symptoms and signs of cADRs in an epileptic clinic every 2 weeks. AEDs tolerance was defined as patients who were able to tolerate AEDs without cADRs manifestation. If cADRs manifested, the AEDs were discontinued immediately and a dermatologist was consulted to diagnose and treat the patients (Figure 1).
Two attending or one chief physician from the Department of Dermatology examined the patients. The criteria for the diagnosis and classification of cADRs were as follows: ① MPE: a rash, not involving the mucosa, no organ or system damage, and resolved after 1–2 weeks; ② HSS: in addition to skin rash, numerous viscera involvement with systemic manifestations, such as fever, arthralgia, eosinophilia, and lymphadenopathy; ③ SJS: the occurrence of skin exfoliation, involving a range of no <10% of the body area, with or without other organ or system damage; ④ TEN: the presence of skin exfoliation, involving more than 30% of the body area, with or without other organ or system damage; and ⑤ SJS/TEN: the presence of skin exfoliation, involving a range of 10–30% of the total body area. The patients were treated for skin damage based on the severity as determined by a dermatologist after cADRs diagnosis was confirmed. These patients were assigned to the AEDs-cADRs group.
Nested case-control design is the most common way to reduce the costs of exposure assessment in prospective epidemiological studies. They can also reduce the sample size through matching (10 (link)). In this study, 15 patients with epilepsy who developed cADRs were defined as the AEDs-cADRs group. For each patient with AEDs-cADRs, two patients with AEDs tolerance were selected and matched by AEDs, gender, age (±3 years), and ethnicity.