Epilepsy is a common chronic disease of the nervous system, which has certain adverse effects on the cognitive, psychological and social functions of the patients. To date, anti-seizure medications (ASMs) remain the first-line treatment option for epilepsy, but many patients with epilepsy still do not have effective seizure control when multiple ASMs are used in combination. Therefore, there is an urgent need for a new target and mechanism ASMs to bring about new treatment options and hope for patients with intractable epilepsy. Perampanel, a new third-generation ASMs, whereas second-generation ASMs tend to exert anti-seizure effects mainly by regulating ion channels or enhancing related mechanisms such as gamma-aminobutyric acid (GABA) effects, perampanel exerts its effects mainly by targeting the excitatory neurotransmitter glutamate. Perampanel is the first selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist and the first selective inhibitory ASMs for excitatory postsynaptic function. Because of its unique target and mechanism, it has been approved by many countries in the world for adjuvant additive therapy and monotherapy for patients with focal and general epilepsy. In addition, with the discovery of the neuroprotective, antioxidant, neurotransmitter regulation effects of perampanel, it also provides a new potential choice for the treatment of other diseases. This article mainly reviews the mechanism of action, pharmacokinetics, clinical trials and treatment of other diseases other than epilepsy of perampanel.
ObjectiveTo evaluate the clinical efficacy and safety tolerance of perampanel in the treatment of Chinese adult epilepsy patients. Methods Clinical data of adult epileptic patients treated with perampanel in Department of Neurology, China-Japan Union Hospital of Jilin University from January 2020 to December 2022 were analyzed retrospectively by self-control method, including demographic and clinical characteristics of patients, changes of epileptic seizures before and after perampanel treatment and adverse events during the treatment of perampanel. To evaluate the clinical efficacy and safety of perampanel in Chinese adult epileptic patients. Results A total of 69 adult epileptic patients with complete follow-up data were included. The dosage range of perampanel was 2 ~ 8 mg. The total effective rate was 68.1%, and the seizure-free rate was 17.4%. The most common adverse reactions were mood change and dizziness, the incidence of adverse reactions was 52.2%, and the incidence of serious adverse reactions was 0.0%. In terms of analysis of influencing factors of efficacy, the results showed that single drug therapy or combination therapy, type of combined antiepileptic drug and treatment time of perampanel did not affect the efficacy (P>0.05), while dosage was an important factor affecting the efficacy of perampanel (P<0.05), and there was no significant difference in efficacy between the focal epilepsy group and the general epilepsy group (P>0.05). In terms of the analysis of factors related to the occurrence of adverse reactions, the results showed that the occurrence of adverse reactions was related to the dosage of perampanel (P<0.05), and was independent of whether it was monotherapy, the addition time of perampanel and the type of combined antiepileptic agents (P>0.05). Conclusion Perampanel has good efficacy and safety tolerance in the treatment of epilepsy in Chinese adults. Both monotherapy and additive therapy can effectively control seizures, and has a good effect on different seizure types. The most common adverse events during treatment were mood changes and dizziness, which could be alleviated and tolerated by most patients with prolonged treatment.
Perampanel (PER) is a third-generation novel anti-seizure drug, a postsynaptic neuronal (α-Amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid, AMPA) receptor antagonist, which effectively controls seizures by inhibiting glutamate-induced neurological hypertransmission. PER can not only be used for the addition of focal epilepsy 4 years old and above, but also monotherapy for children (≥ 4 years old) for the treatment of focal epilepsy patients, its efficacy and safety is relatively good, has been used clinically in many countries, the article overviewed the pharmacokinetics, mechanism, and the addition and monotherapy in different epilepsy types of childhood epilepsy and other aspects, in order to provide a reference for clinical medication, and provide individualized treatment for children with epilepsy.
Objective To observe the efficacy and adverse reactions of pirenpanet in patients with refractory epilepsy treated with add-on therapy. MethodsForty-one patients with medically refractory epilepsy were selected from January 2021 to December 2021 in the Department of Epilepsy of Jiamusi Central Hospital, among which 25 males and 16 females. The self-control study was conducted before and after the treatment with pirenpanet. The observation period was 1 year, and the clinical efficacy, platelet, liver and kidney function and EEG discharge index were observed at 6 months and 12 months respectively. Changes in seizure frequency after treatment were divided into the following 3 groups: effective control: no seizure; effective: seizures reduced by 50% ~ 99%; Ineffective: < 50% reduction in seizures or exacerbation. Results Among the 41 patients with drug-refractory epilepsy, 8 (8/41, 19.51% P < 0.05) were seizure-free, 17 (17/41, 41.46% P < 0.05) were effective, and the total effective rate was (25/41, 60.98%); Sixteen cases (16/41, 39.02%) were ineffective. There were 31 children in 41 cases (31/41, 75.61%), of which 18 cases (18/31, 58.06%) were effective, 16 cases (16/31, 51.61%) had mental and motor retardation, and 8 cases (8/16, 50%) were effective; There were 10 adults (10/41, 24.39%) and 7 effective patients (7/10, 70%). After one year's treatment, the EEG changes of the patients were observed, and the abnormal discharge of 6 patients was reduced according to the discharge index, 2 patients had no abnormal discharge, and the other patients had no obvious EEG changes. Conclusion Pirenpanet is effective and safe as an add-on therapy for medically refractory epilepsy.
ObjectiveTo compare the efficacy and safety of perampanel (PER) and oxcarbazepine (OXC) monotherapy in the treatment of newly diagnosed focal epilepsy in adults. Methods A total of 62 adult patients with focal epilepsy, aged 18~79 years old, with an average age of (40.53±16.69) years, were enrolled from Qingyuan People’s Hospital between August 2021 and October 2022 and randomly divided into PER group and OXC groups. Both groups were followed up for 12 months and assessed for seizure free rate, effective rate, drug retention rate, and adverse reactions at 3, 6, and 12th months. ResultsThe results showed that the seizure free rate, effective rate, and drug retention rate in the PER group were 62.5%, 71.9% and 87.5% at 3 months, respectively, and 53.1%, 65.6% and 75.0% at 6 months respectively. In the OXC group, the seizure free rate, effective rate, and drug retention rate were 70.0%, 86.7%, and 93.3% at 3 months, respectively, and 66.7%, 73.3% and 83.3% at 6 months, respectively. At 12 months, the seizure free rate, effective rate and retention rate of the PER group were 43.8%, 46.9%, and 53.1%, respectively; The seizure free rate, effective rate, and retention rate of OXC group were 66.7%, 66.7%, and 70.0%, respectively. The incidence of adverse reactions in the PER group and OXC group was 15.6% and 16.7%, respectively. The most common adverse reactions in both groups were dizziness and drowsiness, with no serious adverse events. ConclusionPER and OXC monotherapy demonstrated similar efficacy and safety in the treatment of newly diagnosed adult focal epilepsy, and both drugs can be used as safe and effective treatment options.
ObjectiveIn order to evaluate the efficacy, safety and tolerability of adjunctive perampanel in children with refractory epilepsy. MethodsThis study collected medical records of 34 children with refractory epilepsy, who were admitted to Children’s Hospital of Soochow University from January 2020 to January 2021. By comparing the baseline status with the status at 4, 8, 12, 24, 36, and 48 weeks of follow-up, the efficacy and adverse reactions of perampanel were evaluated. ResultsThe mean age of the patients treated with perampanel was 8.1±4.1 years. The male-to-female ratio was 1: 1. After the addition of perampanel, the average responder rate at the 4th, 8th, 12th, 24th, 36th, 48th weeks were 37.5%, 46.7%, 50.0%, 47.4%, 53.8%, 42.9%. The adverse events were reported by 32.4%, and the retention rate was 88.2%. ConclusionsPerampanel has good efficacy, safety and tolerability in the treatment of refractory epilepsy. Moreover, personalized treatment and better baseline seizure control may increase the effectiveness and retention rate of perampanel.
Objective To study the efficacy and adverse events of adjunctive perampanel in children with refractory epilepsy. Methods A prospective study was carried out in 45 children with refractory epilepsy, who were treated in our hospital from January 2020 to February 2021 using perampanel as an add-on treatment, with a criteria for enrollment and the starting dose of perampanel. Follow-up would be taken at once a month. Afte 3 months would check blood routine, liver function, kidney function and humoral immunity. The EEG was reviewed after 6 months. The initial dose of perampanel was 0.04 mg/(kg·d) (the maximum didn't exceed 2 mg/d), increasing by 0.04 mg/(kg·d) every two weeks, and the maximum maintenance dose didn't exceed 6 mg/d. The efficacy and adverse reactions of perampanel were evaluated by comparing the seizure frequency and EEG results before and after a 6-month add-on therapy.ResultsAmong the 45 children,complete seizure control was achieved in 7 cases after the therapy, and the seizure attacks were reduced in 26 cases, showing a total response rate of 73.3%. After the treatment, the epileptiform discharge of 28 children was reduced, and the effective rate was 62.22%. During the observation period, all the blood routine, liver function, kidney function,and humoral immunity of the children were normal.10 cases of adverse reactions occurred after the additional treatment of perampanel, and the adverse reaction rate was 22.22%. Conclusions Perampanel has good efficacy and safety in the add-on treatment of refractory epilepsy.
Anti-seizure medications (ASMs) are the most important and basic treatment for epilepsy, and are also the first choice for epilepsy treatment, but about one-third of patients have drug resistance. Perampanel (PER), as a novel third generation ASMs, inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) through non-competitive inhibition. AMPA plays an anti-seizure role. Since its approval in China in 2021, it has been mainly used in the treatment of focal epilepsy (with or without general seizure) as a single drug or addition, and has good safety, effectiveness and tolerability. Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common childhood focal epilepsy syndrome, accounting for 15% ~ 25% of various childhood epilepsies, PER has important advantages in clinical studies and has shown certain curative effect. At the same time, the overall effect of PER on cognition was neutral, with no systemic cognitive deterioration or improvement. In view of the relatively short application time of PER, which is still a new drug, this article will review the mechanism of action, dose, add-on (single drug) treatment, adverse events and, in order to provide clinicians with more drug choices and facilitate the individualized diagnosis and treatment of epilepsy.