Preliminary evidence about irritability in patients with epilepsy treated by perampanel as first add-on therapy compared to levetiracetam and valproic acid

Aims: Irritability has been described as a frequent adverse event in patients affected by epilepsy and treated with perampanel (PER), levetiracetam (LEV), and less frequently with valproic acid (VPA). Since the questionnaire for irritability (I-EPI) is a validated instrument to measure this psychiatric manifestation in patients affected by epilepsy, in this study we aimed at investigating the effect of PER as first add-on therapy on I-EPI. Moreover, we compared the effectiveness and I-EPI scores obtained at 12-month follow-up visits in patients treated by PER, LEV, or VPA in order to measure irritability as a consequence of these treatments. Methods: We collected data from 17 patients treated by PER, 16 patients treated by LEV, and 16 patients under VPA treatment followed for 12 months. Results: We did not document significant changes of I-EPI questionnaire between baseline and follow-up in the PER group. As concerning the comparison of I-EPI among PER, LEV, and VPA groups, we documented lower global scores in PER than both LEV (P < 0.05) and VPA (P < 0.05) groups. Moreover, patients under PER treatment showed lower scores than LEV and VPA (P < 0.05) in I-EPI items measuring the gentle personality, anxiety of having epileptic seizures in front of others, and irritability in thinking that they can have an epileptic seizure. Conclusions: This retrospective study described a stable and possibly lower degree of irritability in patients starting PER than LEV and VPA treatments, although we documented the comparable effectiveness of PER, LEV, and VPA as first add-on treatments in patients affected by uncontrolled epileptic seizures. However, the small sample of patients included in this study and the absence of I-EPI scores obtained at baseline visits in LEV and VPA groups require further investigations to confirm this preliminary evidence.