Objective: The purpose of this literature study was to evaluate the effect of perampanel as an adjunct therapy in patients, 12 years of age or older suffering from pharmacoresistant epilepsy. Methods: This thesis is a literature work based on scientific articles sought and obtained from the medical database PubMed. The five articles were selected with the criteria that perampanel is used for therapy-resistant epilepsy, as an adjunct therapy in patients who do not respond to other anti-epileptic drugs, in patients using 1-3 antiepileptic drugs, participants 12 years or older and the drug is used in humans. The result measured was the percentage change in seizure rate per 28 days and ≥ 50% responder rate. Results: Study 1 and 5 compared the effect and safety of different doses of perampanel with placebo. A statistically significant change in seizure rates was shown in the perampanel group, 34.5% for 8 mg/day and 26.3% for 12 mg/day, compared to placebo 21.0%. The impact of perampanel in study 5 also showed a statistically significant difference in responder rate in perampanel group, 64.2% compared to placebo 39.5%, study 1 showed no statistically significant difference here. Study 2 evaluated the safety and tolerability of long-term treatment of perampanel up to 12 mg/day. In each 13-week interval of perampanel treatment, the overall median percentage reduction was 39.3% for 14-26 weeks (n=1,114), 46.5% for weeks 40-52 (n=731) and 58.1% for weeks 92104 (n=59). Similarly, in the case of the decrease in the responder rate of 41.4%, 46.9% and 62.7% for the respective 13-week intervals. Study 3 compared the efficacy and safety of perampanel with placebo. A statistically significant change in seizure rates was shown in perampanel group, -34.8% for 8 mg/day and -35.6% for 12 mg/day compared to placebo who had -18.0%. An increase of the 50% responder rate was also seen in the perampanel group, 40.9% for 8 mg/day and 45.0% for 12 mg/day. In Study 4, the effect and safety of perampanel were evaluated in patients who had received placebo in previous Phase III double-blinded core studies and switched to perampanel in extension study 307. The percentage decrease in the overall seizure rate in double blinded studies increased from 18.6% to 44.3% for placebo group and from 31.7% to 41.4% for perampanel group. Responder rate for placebo was 20.3% increased to 44.3% and perampanel was 34.0% increased to 43.4% in the double blinded studies. Conclusions: All included studies analyzed the effect on seizure frequency, tolerability and adverse reactions. Studies 1–5 showed a clear decrease in seizure rates. But it was also found that there were differences between the youth group and the study pool both as a whole as well as at different doses. The question in this literature study can thus be answered with yes, perampanel has a positive effect as an adjunct therapy against therapy-resistant epilepsy. However, it is of great importance that the dose and titration are adjusted individually.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23757号 / 医博第4803号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 岩田 想, 教授 上杉 志成 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13608号 / 論医博第2318号 / 新制||医||1073(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 村井 俊哉, 教授 高橋 淳 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM