New Antiepileptic Drugs: Focus on Ezogabine, Clobazam, and Perampanel

Rudzinski, Leslie A.; Velez‐Ruiz, Naymee; Gedzelman, Evan; Mauricio, Elizabeth A.; Shih, Jerry J.; Karakis, Ioannis

doi:10.1136/jim-2016-000151

Cited by 19 publications

(14 citation statements)

References 106 publications

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“…as carbamazepine, oxcarbazepine, and phenytoin significantly increase the clearance of perampanel and decrease its plasma concentration. 15,16 Perampanel has been studied in the presence of various AEDs, including enzyme-inducing AEDs, and there have been improved treatment outcomes regardless of the types of concomitant AEDs despite the known interaction between perampanel and enzyme-inducing AEDs. 17,18 Unlike in previous studies, our patients were not affected by concomi-tant enzyme-inducing AEDs.…”

Section: Jcnmentioning

confidence: 99%

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study

et al. 2020

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Background and Purpose The US Food and Drug Administration approval for perampanel has only recently been expanded to patients as young as 4 years, and so there have been few real-life studies of the effects of perampanel in pediatric patients. The aim of this study was to determine the long-term efficacy, factors affecting treatment response, and tolerability of perampanel as an add-on therapy in pediatric patients aged 4 years or older with epilepsy. Methods This multicenter retrospective observational study collected data from pediatric epilepsy centers of four Korean national universities. Changes in the seizure frequency from baseline, adverse events, and retention rates were obtained at 3, 6, and 12 months. Adverse events and discontinuation profiles were obtained to assess tolerability. Results This study included 220 children and adolescents (117 males and 103 females) aged 4 to 20 years. The overall response rate was 43.6%, and the seizure-freedom rate was 17.7%. Factors affecting a good treatment response were the absence of intellectual disability, small number of concomitant antiepileptic drugs, and low baseline seizure frequency. Eighty-eight patients (40%) experienced adverse events, but they mostly were of mild severity and resolved after the dose reduction or discontinuation of perampanel. The retention rates at 3, 6, and 12 months were 85.0%, 71.8%, and 50.5%, respectively. Conclusions Adjunctive treatment with perampanel was efficacious and tolerated in pediatric patients aged 4 years or older with epilepsy. Early perampanel treatment may help to reduce the burden of their seizures and improve their quality of life.

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Section: Jcnmentioning

confidence: 99%

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study

et al. 2020

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“…PER reduces calcium inward currents through AMPA receptors in cortical and subcortical brain regions. Some data suggest that it also acts on NMDA and kainate receptors [103]. PER is one of the newest AEDs, and presently, there is no evidence that it acts on other pharmacological targets.…”

Section: Possible Neuropharmacological Mechanisms Of Aed-induced Amentioning

confidence: 99%

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Hansen

Ljung

Brodtkorb

et al. 2018

Behavioural Neurology

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Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and “alternative psychosis” and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.

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“…Therefore, pharmacoresistant patients require AEDs with novel mechanisms of action [3]. Perampanel, one of the latest AEDs, is the first α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist [4].…”

Section: Introductionmentioning

confidence: 99%

“…Perampanel inhibits AMPA-induced increases in intracellular Ca 2+ and selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing neuronal excitation [5]. Perampanel is primarily metabolized by CYP3A4 of the P450 enzyme system, and enzyme-inducing drugs such as carbamazepine, oxcarbazepine, and phenytoin significantly increase the clearance of perampanel and decrease its plasma concentration [3,6].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy

et al. 2019

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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.

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New Antiepileptic Drugs: Focus on Ezogabine, Clobazam, and Perampanel

Cited by 19 publications

References 106 publications

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study

Real-Life Effectiveness and Tolerability of Perampanel in Pediatric Patients Aged 4 Years or Older with Epilepsy: A Korean National Multicenter Study

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Efficacy and tolerability of adjunctive perampanel treatment in children under 12 years of age with refractory epilepsy

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