Examining aggressive behavior in patients with epilepsy under treatment with Levetiracetam, Brivaracetam and Perampanel: a comparison to healthy controls

Introduction: Epilepsy is frequently associated with behavioral and emotional difficulties. Among antiseizure medications, Levetiracetam, Perampanel, and Brivaracetam are notorious to cause behavioral adverse drug reactions, including increased anger, irritability, and aggression. While these effects are often described in self-report data, experimental studies examining aggressive behavior in patients with epilepsy are scarce. This study aims to assess aggression in patients with epilepsy and compare it to healthy controls, using self-report measures and two experimental provocation paradigms. Methods: Thirty seven patients with epilepsy treated with Levetiracetam, Perampanel, or Brivaracetam (with an overrepresentation of patients treated with Levetiracetam) and 38 healthy controls completed the Buss and Perry Aggression Questionnaire, Barratt Impulsiveness Scale, Beck's Depression Inventory, and Affective Style Questionnaire. Aggressive behavior and reaction were investigated using a modified version of the Taylor Aggression Paradigm and the Technical Provocation Paradigm, alongside with emotional state ratings during the paradigms. Results: Patients with epilepsy reported higher aggression, impulsivity, and depression in the self-report questionnaires compared to healthy controls. However, behaviorally, patients did not show increased aggression. Instead, they showed reduced emotional reactivity to provocation, with lower changes in the emotional state ratings. Higher desire for revenge and higher frustration during the task predicted stronger aggressive responses in the patient group, but not in the control group. Discussion: Our findings suggest reduced emotional responsiveness to provocation, and a discrepancy between self-perceived and observed aggression in patients with epilepsy. Aggressive responses in this group appeared to be influenced by situational emotions such as revengefulness and frustration. These results underline the need to differentiate between subjective and observable behavioral changes in patients with epilepsy, and of considering the impact of psychiatric comorbidities and emotion regulation difficulties.