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Sleep disorder, migraine, cognitive and behavioral disorders, anxiety and depression are common comorbidities of epilepsy. The comorbidity rate of epilepsy patients is eight times that of the general population, which affects the prognosis and quality of life of epilepsy patients. Perampanel (PER), as a third-generation antiseizure medication, has shown promising clinical research and application in the treatment of comorbidities in epilepsy. PER can improve the total sleep time, sleep latency and sleep efficiency of patients with epilepsy comorbid sleep disorder. PER also shows good efficacy in reducing seizure and migraine attacks of patients with epilepsy comorbid migraine. Meanwhile, the impact of PER on overall cognitive characteristics is neutral, with no systematic cognitive deterioration or improvement, but behavioral changes are one of the most common adverse events related to PER. For patients with comorbid anxiety and depression, PER does not exacerbate the anxiety and depression of epilepsy patients, and the severity of anxiety and depression in some patients will improve. This article will review the mechanism of action and clinical treatment research progress of PER on comorbidities of epilepsy.
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OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.
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Objective:To observe the clinical effect of Perampanel on the add-on therapy in children with drug-resistant epilepsy.Methods:Clinical data of children with drug-resistant epilepsy treated with add-on therapy of Perampanel in the Department of Pediatrics, Fujian Medical University Union Hospital from January to June 2020 were retrospectively analyzed, aiming to assess the therapeutic efficacy of Perampanel on the add-on therapy of drug-resistant epilepsy.The self-control effective rate of Perampanel before and after treatment were counted.Results:A total of 20 cases of 2-12 year-old children with drug-resistant epilepsy were collected, including 14 males and 6 females.Their mean age, age of onset and course of disease were (5.82±2.39) years, (3.41±1.96) years and (2.40±1.48) years, respectively.Among them, 1 case had simple partial seizures, 7 cases had complex partial seizures, 1 case had generalized seizures and 5 cases had epilepsy syndromes, there were 6 cases with undetermined seizure attack.After 3-month add-on therapy of Perampanel, 4 cases of children with drug-resistant epilepsy were seizure-free, 8 cases had the reduced frequency of seizure for 50% or more, 2 cases had the reduced duration of seizure, 1 case had the reduced severity of seizure, while 4 cases did not respond to perampanel and 1 case was aggravated.Based on the criteria of reduced frequency of seizure for more than 50%, the therapeutic efficacy of add-on therapy of Perampanel achieved 60% in children with drug-resistant epilepsy.Conclusions:The third generation of anti-seizure medication Perampanel can effectively reduce the frequency of seizure, especially in the elder children and those with certain epilepsy syndromes.
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The new antiepileptic drugs perampanel,retigabine,rufinamide and stiripentol have been recently approved for different epilepsy types.Being them an innovation in the antiepileptics armamentarium,a lot of investigations regarding their pharmacological properties are yet to be performed.Besides,considering their broad anticonvulsant activities,an extension of their therapeutic indications may be worthy of investigation,especially regarding other seizure types as well as other central nervous system disorders.Although different liquid chromatographic (LC) methods coupled with ultraviolet,fluores-cence,mass or tandem-mass spectrometry detection have already been developed for the determination of perampanel,retigabine,rufinamide and stiripentol,new and more cost-effective methods are yet required.Therefore,this review summarizes the main analytical aspects regarding the liquid chro-matographic methods developed for the analysis of perampanel,retigabine (and its main active metabolite),rufinamide and stiripentol in biological samples and pharmaceutical dosage forms.Furthermore,the physicochemical and stability properties of the target compounds will also be addressed.Thus,this review gathers,for the first time,important background information on LC methods that have been developed and applied for the determination of perampanel,retigabine,rufinamide and stiripentol,which should be considered as a starting point if new (bio)analytical techniques are aimed to be imnlemented for these drugs.
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PURPOSE: There is limited data on the use of perampanel in children under 12 years of age. We evaluated the efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy. METHODS: This retrospective observational study was performed in Kyungpook National University Hospital from July 2016 to March 2018. A responder was defined as a patient with ≥50% reduction in monthly seizure frequency compared with the baseline. Adverse events and discontinuation data were obtained to evaluate tolerability. RESULTS: Twenty-two patients (8 males, 14 females) aged 3.1–11.4 years (mean, 8.0±2.5 years) were included in this study. After an average of 9.2 months (range, 0.5–19 months) of follow-up, 15 patients (68%) showed a reduction in seizure frequency, including 5 patients (23%) with seizure freedom. The age at epilepsy onset was significantly lower (P=0.048), and the duration of epilepsy was significantly longer (P=0.019) in responders than in nonresponders. Nine patients (41%) experienced adverse events, including somnolence (23%), respiratory depression (9%), violence (4.5%), and seizure aggravation (4.5%). The most serious adverse event was respiratory depression, which required mechanical ventilation in 2 patients (9%). Eight patients (36%) discontinued perampanel due to lack of efficacy or adverse events. Three out of 4 patients (75%) who discontinued perampanel due to adverse events had an underlying medical condition. CONCLUSION: Perampanel offers a treatment option for refractory epilepsy in children. Adjunctive treatment with perampanel requires special consideration in those with underlying medical conditions to prevent serious adverse events.
Subject(s)
Child , Humans , Male , Epilepsy , Follow-Up Studies , Freedom , Observational Study , Respiration, Artificial , Respiratory Insufficiency , Retrospective Studies , Seizures , ViolenceABSTRACT
BACKGROUND AND PURPOSE: Perampanel is the first α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist developed to treat epilepsy. The effects of either rapid or slow dose titration on adverse events remain to be elucidated. METHODS: Eighty-five patients received perampanel between March 2016 and August 2016. Patients were divided into two groups according to their dosing schedule: rapid dose titration (2-mg increments at intervals of 1 to 2 weeks) and slow dose titration (2-mg increments at intervals of at least 3 weeks). Seizure frequency and adverse events were analyzed over 3 months. RESULTS: Adverse events were reported by 47 (58%) of the 81 patients analyzed, with 12 (15%) patients discontinuing perampanel due to adverse events. Common adverse events included dizziness (n=30, 37%), aggressive mood and behavior (n=19, 24%), gait disturbance (n=16, 20%), and sleep problems (n=10, 12.4%). The overall adverse events were similar in the slow-titration group (38 of 61 patients) and the rapid-titration group (8 of 20 patients, p=0.081). However, none of the 20 patients in the slow-titration group experienced gait disturbance, compared with 16 of the 61 patients in the rapid-titration group (p=0.009), while appetite change was experienced by 4 patients in the slow-titration group but only 1 in the rapid-titration group (p=0.003). No relationship was noted between adverse events and the maximum dose of perampanel (p=0.116). Sex differences were observed, with the response to perampanel being better and the rate of adverse events being higher in females (p=0.015 and p=0.046, respectively). CONCLUSIONS: Slow titration of perampanel may reduce perampanel-related adverse events.
Subject(s)
Female , Humans , Appetite , Appointments and Schedules , Dizziness , Drug Resistant Epilepsy , Epilepsy , Gait , Seizures , Sex CharacteristicsABSTRACT
Objective o evaluate the efficacy and safety of perampanel in the treatment of refractory partial-onset seizures.Methods The randomized controlled trials ofperampanel in treatment of refractory partial-onset seizures were searched from PubMed,EBSCO,EMbase,Cochrane Library,CBM,CNKI,VIP database,and Wanfang database by computer.Data were collected from establishment of the database to February 2017 and the each index was analyzed by meta-analysis with RevMan 5.0 software.Results Five RCT were included,including 1 500 patients with refractory partial-onset seizures.Meta-analysis results showed that there was a significant difference between perampanel and placebo in term of seizure-free rate [OR=3.75,95％CI(1.77,7.93),P =0.000 6] and percentage of patients achieving 50％ reduction in seizure frequency [OR=2.08,95％CI(1.69,2.56),P ＜ 0.001].Common adverse reactions of perampanel were dizziness,somnolence,headache,ataxia,nasopharyngifis,etc.The total rate of adverse reactions of the two Perampanel groups of 8 mg group and 12 mg group doses were higher than placebo group (P ＜ 0.05).Conclusion The clinical efficacy of perampanel in the treatment of refractory partial-onset seizures,and the adverse reactions is slight,patient is well tolerated.
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Objective o evaluate the efficacy and safety of perampanel in the treatment of refractory partial-onset seizures.Methods The randomized controlled trials ofperampanel in treatment of refractory partial-onset seizures were searched from PubMed,EBSCO,EMbase,Cochrane Library,CBM,CNKI,VIP database,and Wanfang database by computer.Data were collected from establishment of the database to February 2017 and the each index was analyzed by meta-analysis with RevMan 5.0 software.Results Five RCT were included,including 1 500 patients with refractory partial-onset seizures.Meta-analysis results showed that there was a significant difference between perampanel and placebo in term of seizure-free rate [OR=3.75,95％CI(1.77,7.93),P =0.000 6] and percentage of patients achieving 50％ reduction in seizure frequency [OR=2.08,95％CI(1.69,2.56),P ＜ 0.001].Common adverse reactions of perampanel were dizziness,somnolence,headache,ataxia,nasopharyngifis,etc.The total rate of adverse reactions of the two Perampanel groups of 8 mg group and 12 mg group doses were higher than placebo group (P ＜ 0.05).Conclusion The clinical efficacy of perampanel in the treatment of refractory partial-onset seizures,and the adverse reactions is slight,patient is well tolerated.