Specific adverse effects of antiepileptic drugs - a true-to-life monotherapy study

Abstract Background In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy. Methods All patients ≥ 16 years of age with epilepsy for ≥ 12 months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database. Results Out of 841 patients, 438 (61% female, mean age: 44.7 ± 17.1 years) on monotherapy were included in this study. Levetiracetam (n = 151), lamotrigine (n = 167), valproic acid (n = 73), or controlled-release carbamazepine (n = 47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score ≥ 45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands. Conclusion Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.