Differences in aggression as psychiatric side effect of levetiracetam and perampanel in patients with epilepsy

Aggression is the most commonly encountered antiepileptic-drug (AED)-induced psychiatric adverse effects. Levetiracetam (LEV) is well known to be associated with increased rates of aggression, while perampanel (PER) is also recognized as a potentially aggression-promoting agent, though opinions vary. However, few studies have addressed questions regarding whether the nature of irritability-aggression differs between those drugs. The present study used a standardized rating scale to examine aggression among patient with epilepsy who received LEV or PER using specific measures to confirm the effects of the drugs.We enrolled 144 consecutive outpatients receiving treatment for epilepsy with LEV (n = 103) or PER (n = 41), and determined their effects regarding aggression using the Buss-Perry Aggression Questionnaire (BAQ). For analysis, total BAQ scores for the LEV and PER subjects were compared to determine whether the aggression-promoting effects of the agents differed, and which BAQ subdomains (physical aggression, verbal aggression, anger, hostility) were related to production of aggression in patients taking either LEV or PER. As a subsidiary analysis, clinical variables inclusive of administered AED type that showed a significant impact on BAQ scores were determined.The LEV group had a significantly higher hostility score (19.4 ± 5.8) as compared to the PER group (17.2 ± 6.3) in subscale analysis (p < 0.05). In multiple regression analysis, LEV had a significant association with higher hostility score (P = 0.006).Our results indicate that while easily visible outward-directed aggression tends to be dominant in patients given PER, aggression provoked by LEV may be felt more subjectively or in an inward-directed manner, which can lead to more diverse expression and misrecognition.