A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment

Purpose: The objective of this work was to review systematically the efficacy and tolerability of perampanel (PER) in residential patients of an epilepsy center. Method: We adopted an industry-independent noninterventional retrospective evaluation on the basis of the paper and electronic records complemented by personal information on the part of the treating neurologists. All patients (N = 26, 15 females, mean age: 30, range 21-55 years) started on PER from its introduction to the market in September 2012 until December 15th 2013 were included. Evaluation was carried out after 6, 12, and 24 months of PER treatment. Changes in seizure frequency were calculated as the number of seizures during three months on PER compared to a three-month baseline period. The Clinical Global Impression Scale served as an instrument to record changes in seizure intensity beyond numerical values. Adverse effects were documented by means of the Liverpool Adverse Events Profile. Results: Most patients had structural or metabolic epilepsy, 2 patients suffered from Lennox-Gastaut syndrome, 2 from other symptomatic generalized epilepsy. All patients had grade III drug-resistant epilepsy. All patients had additional cognitive deficits of different degree. The retention rates were 61.5% after 6 months, 46.2% after 12 months, and 42.3% after 24 months. The responder rates were 11.5% after 6 months, 23.1% after 12 months, and 7.7% after 24 months. Partial responders (positive CGI and/or seizure reduction <50%) included, the respective values were 26.9%, 38.5%, and 23.1%. Only 1 patient was seizure free at 12 months (but not at 24 months). A loss of efficacy in the second year of treatment was suspected but the decrease of the responder rate could also be ascribed to a number of different circumstances. Adverse effects in the psychiatric field like irritability, aggression, increased sensitivity, and suicidal ideation/behavior occurred in 50% of the patients. They were the main reason to discontinue PER. Conclusions: After one year of treatment PER showed reasonable efficacy in a particularly difficult-to-treat population. Psychiatric adverse effects forced discontinuation in many cases. (C) 2016 Elsevier Inc. All rights reserved.