Fycompa (perampanel) / Eisai, Grupo Biotoscana, Catalyst Pharma, Angelini Group - LARVOL DELTA

Targeting cortical hyperexcitability with phenytoin improves autism spectrum disorder-like phenotypes (Neuroscience 2026) - "These findings suggest that phenytoin, but not carbamazepine, lamotrigine or perampanel, ameliorates abnormalities in the open field test in VPA-exposed mice. Moreover, the therapeutic effects observed with phenytoin may reflect mechanisms beyond a general reduction in cortical excitability."

CNS Disorders • Epilepsy

Ion Channel-Targeting Modulators in Glioma: Pharmacological Advances and Therapeutic Perspectives. (PubMed, Int J Mol Sci) - "This perspective summarizes current evidence for eight representative drugs and phytoconstituents-perampanel, valproic acid, cilostazol, berberine, oxaliplatin, temozolomide, arecoline, and triptolide-that modulate these ion channels. In particular, arecoline is associated with carcinogenicity and neurotoxicity, triptolide with significant systemic toxicity, berberine with poor oral bioavailability and potential drug interactions, and oxaliplatin with dose-limiting neurotoxicity. Overall, this perspective highlights ion channels as promising therapeutic targets in glioma while emphasizing the need for rigorous experimental validation and careful evaluation of safety before clinical translation."

Journal • Review • Brain Cancer • CNS Disorders • Epilepsy • Glioma • Oncology • Solid Tumor

Perampanel improves cognitive function in epilepsy by targeting AMPA receptor subunit GluR2-mediated endoplasmic reticulum stress and synaptic plasticity. (PubMed, Int J Neurosci) - "In terms of mechanism, GluR2 silencing reversed the protective effects of PER in KA-stimulated hippocampal neurons, and further inhibiting ERS using 4-PBA could offset the effects of GluR2 silencing. GluR2-mediated ERS may involve the improved effects of Perampanel in cognitive function of epilepsy patients by promoting synaptic plasticity."

Journal • CNS Disorders • Epilepsy • ATF4 • ATF6 • DLG4 • HSPA5

Perampanel as a candidate for polytherapy in Stage 1 Plus status epilepticus: biological rationale and translational limits. (PubMed, Neurol Sci) - "Receptor-trafficking models provide a biologically plausible and timing-aligned rationale for BDZ plus AMPA antagonism. Early BDZ plus PER is therefore biologically plausible and deserves prospective testing, but rapid achievement of therapeutic exposure within the proposed S1P window may be limited by enteral administration, and current human evidence is insufficient to support its clinical use in S1P."

Journal • Review • CNS Disorders • Epilepsy

Potential Role of CYP3A4 in Determining In Vivo Exposure to Cannabidiol (CBD) and its Active Metabolite 7-OH-CBD: Evidence from an In Vitro Study. (PubMed, Eur J Drug Metab Pharmacokinet) - "ASMs with CYP3A4-inhibitory potential may alter systemic exposure to both CBD and its active metabolite, 7-OH-CBD, as demonstrated in vitro. However, co-administration of CBD with CYP3A4-substrate ASMs or CYP2C19 inhibitors is predicted to result in only modest increases in CBD exposure."

Journal • Preclinical • CNS Disorders • Epilepsy • CYP2C19 • CYP2C9 • CYP3A4

Novel SLC6A9 variants in an adult presenting with GlyT1 encephalopathy. (PubMed, J Hum Genet) - "Perampanel was of significant benefit for the exaggerated startle. Significant visual loss is unexplained. It may relate to the essential role of GlyT1 in retinal amacrine cells, although this mechanism remains speculative."

Journal • CNS Disorders • Rare Diseases • Respiratory Diseases

Risk of hostility and aggression with perampanel monotherapy versus combination therapy in pediatric epilepsy: A Japanese post-marketing database study using a nested case-control design. (PubMed, Epileptic Disord) - "The safety profile of perampanel in routine pediatric practice was consistent with prior clinical trial data. The potential for hostility- and aggression-related adverse events warrants caution, but rates did not differ between perampanel as monotherapy vs. in combination with other ASMs. This study also demonstrated the feasibility of integrating physician-reported outcomes into post-marketing surveillance using a real-world database, providing detailed insights beyond standard medical information."

Journal • Monotherapy • P4 data • CNS Disorders • Epilepsy • Mood Disorders • Pediatrics • Psychiatry

Perampanel in real-world epilepsy setting: results from the PERSICILIA study. (PubMed, Epilepsy Behav) - "Neuropsychiatric comorbidity was also strongly associated with adverse events (OR 6.01, p < 0.001). These results support sustained real-world effectiveness and manageable tolerability of perampanel across heterogeneous centres and patient subgroups, highlighting the importance of monitoring comorbidities and concomitant therapy adjustments, and suggesting potential benefits beyond seizure control."

Journal • Real-world evidence • CNS Disorders • Epilepsy • Psychiatry

Gestational Changes in Antiseizure Medication Concentrations and the Impact of Polytherapy: A Prospective Multicenter Cohort Study in China. (PubMed, Neurology) - P=N/A | "Pregnancy was the primary driver of declining C/D ratios, and concomitant ASMs and body weight acted as secondary modifiers. These findings support individual therapeutic drug monitoring."

Journal • Observational data • CNS Disorders • Epilepsy

Narrative Review: Efficacy, Safety, and Tolerability of Newer Third-Generation Antiseizure Medications for Focal Epilepsy: A New Benchmark in Treatment Outcomes? (PubMed, Neurol Ther) - "All third-generation ASMs were effective adjunctive therapies. Cenobamate was associated with higher responder and seizure freedom rates and higher long-term retention rates. Brivaracetam and lacosamide had favorable tolerability profiles. The notable seizure freedom rates with cenobamate suggest a potential new benchmark in focal seizure treatment. Comparator trials are needed to confirm possible efficacy and tolerability differences among third-generation ASMs."

Journal • Review • CNS Disorders • Eosinophilia • Epilepsy • Fatigue • Pain • Psychiatry

PEPSTEP: Perampanel for the prevention of post-stroke epilepsy- efficacy and safety (ANZCTR) - P2 | N=164 | Completed | Sponsor: Alfred Health | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • CNS Disorders • Epilepsy

Intravenous perampanel for early post-traumatic seizure prophylaxis across a wide range of traumatic brain injury severity: Potential for low incidence and favorable outcomes in a retrospective cohort. (PubMed, Brain Spine) - "Intravenous PER within 12 h of TBI was associated with low EPTS incidence, favorable outcomes, and few adverse events. Given the retrospective, single-arm design and modest sample size, these preliminary, hypothesis-generating findings warrant evaluation in the ongoing PEACE-TBI trial."

Journal • Retrospective data • CNS Disorders • Epilepsy • Psychiatry • Vascular Neurology

Distinct Roles of NMDA and AMPA Receptors in the Pathogenesis of Hyperbaric Oxygen-Induced Seizures. (PubMed, Biomedicines) - " Male Wistar rats were assigned to seizure-monitoring groups (n = 86) exposed to 100% O2 at 6 ATA until seizure onset: saline control; memantine (1, 5, 25 mg/kg); perampanel (0.2, 1, 5 mg/kg); memantine + perampanel combination (5 + 1 mg/kg); and methionine sulfoximine controls (50, 100 mg/kg). Our findings sharply contrast with the established priority of NMDA glutamate receptors in epileptogenesis, revealing a novel neurochemical mechanism under extreme hyperoxia. We identify fast-acting AMPA receptors as the definitive principal molecular targets for mitigating CNS oxygen toxicity."

Journal • CNS Disorders • Epilepsy • CA3

Cell-based Therapies and Drug Repurposing in Stroke. (PubMed, J Nippon Med Sch) - "Valproic acid, a histone deacetylase inhibitor, and perampanel, a selective AMPA receptor antagonist, target key mechanisms, such as excitotoxicity, oxidative injury, and epigenetic regulation. This review synthesizes the current evidence on both strategies and emphasizes mechanistic overlaps, clinical trial findings, translational barriers, and future directions. Unlike previous reviews that have addressed cell-based therapies or drug repurposing separately, we propose a unique phase-specific integrative framework that rationally combines these complementary strategies with reperfusion therapy and rehabilitation to achieve durable neuroprotection and meaningful recovery in ischemic stroke."

Journal • Cardiovascular • Inflammation • Ischemic stroke

Role of antiseizure medication in postoperative late seizure and survival among patients with newly diagnosed glioblastoma: A multicenter retrospective study. (PubMed, Neurooncol Adv) - "In patients treated with postoperative ASM (levetiracetam [LEV], lacosamide [LCM], or perampanel [PER]), as well as in those who received no medication, the cumulative incidence of late seizure, adverse events, and survival outcomes were analyzed. LEV and PER after glioblastoma surgery were associated with a reduced risk of late seizure compared with LCM or no medication. LEV or PER may be considered as postoperative ASMs to optimize seizure control and potentially help preserve patients' QOL."

Clinical • Journal • Retrospective data • Brain Cancer • CNS Disorders • Epilepsy • Glioblastoma • Oncology • Solid Tumor

Pharmacokinetics, Safety, and Dosing of Antiseizure Medications in Patients with Renal or Hepatic Impairment. (PubMed, Clin Pharmacokinet) - "Ten newer antiseizure medications (ASMs) approved since 2000 and selected for this review (cenobamate, brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, fenfluramine, ganaxolone, cannabidiol, stiripentol, and rufinamide) have broadened treatment options for drug-resistant epilepsy. Regulatory discrepancies between FDA and EMA labeling were identified for all ten agents, notably divergent hepatic dose caps for perampanel and cenobamate, conflicting renal recommendations for fenfluramine, and discordant guidance for eslicarbazepine acetate in severe renal impairment. These agents exhibit no uniform class effect in organ impairment; prescribing must be governed by agent-specific disposition profiles, organ-function severity, and free-drug monitoring for highly protein-bound agents like perampanel and ganaxolone."

Journal • PK/PD data • Review • CNS Disorders • Epilepsy • Hepatology • Nephrology • Renal Disease

KCNA3 Gene Polymorphism Affects the Efficacy and Plasma Concentration of Perampanel in Patients With Refractory Epilepsy. (PubMed, Ther Drug Monit) - "The KCNA3 rs2821557 polymorphism is an important predictor of the therapeutic efficacy of PER in controlling epileptic seizures and a determinant of the attainment of therapeutic plasma PER concentrations."

Journal • CNS Disorders • Epilepsy

Exploring the impact of controlled substance restrictions on epilepsy care in the United States: A neurologist survey. (PubMed, Epilepsy Behav) - "Respondents reported high rates of medication access issues related to controlled substance restrictions and low rates of ASM misuse. Controlled substance restrictions create practical barriers to reliably obtaining scheduled ASM prescriptions that can result in increased risk of morbidity and mortality. Controlled substance restrictions warrant reevaluation for PWE given the specific risk-benefit tradeoffs for this life-threatening neurologic condition."

Journal • CNS Disorders • Epilepsy

Efficacy and sleep impact of perampanel versus levetiracetam monotherapy for SeLECTS: A pilot prospective cohort study. (PubMed, Epilepsy Behav) - "Both LEV and PER monotherapy were tolerated and associated with short-term seizure control in children with SeLECTS. There are some indications that PER may offer small additional benefits for the sleep architecture, resulting in a decrease in the proportion of N1 and NAW. However, prospective studies with longer follow-up are needed to confirm the observations."

Journal • Monotherapy • CNS Disorders • Epilepsy

PROSPER: PeRampanel fOr Status ePilEpticus pRophylaxis Post-cardiac Arrest (clinicaltrials.gov) - P2 | N=52 | Recruiting | Sponsor: University of California, San Francisco | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: May 2026 ➔ May 2027

Trial completion date • Trial primary completion date • Cardiovascular • CNS Disorders • Epilepsy

Perampanel Monotherapy in Epileptic Children: A Systematic Review with Pooled Descriptive Analysis. (PubMed, J Child Neurol) - "The non-randomized nature of the included studies limited the ability to draw definitive causal inferences. In conclusion, perampanel could be an effective initial monotherapy for children diagnosed with epilepsy."

Journal • Monotherapy • CNS Disorders • Epilepsy

Toward individualized precision dosing of perampanel: Integrating therapeutic drug monitoring, drug-drug interactions, and pharmacogenetics. (PubMed, Eur J Pharm Sci) - "Furthermore, it incorporates pharmacogenetic information, such as the CYP3A5*3 polymorphism, as an intrinsic stratification criterion to refine initial dose selection. By synergistically integrating these three dimensions, TDM-guided exposure optimization, DDI-aware dosing, and genotype-informed initiation, this strategy not only enables tailored dosing for vulnerable populations (including children, pregnant women, and patients with renal impairment) but also has the potential to improve overall clinical outcomes, maximizes therapeutic benefit, minimizes safety risks, and enhances the efficiency of healthcare resource utilization."

Biomarker • Journal • Review • CNS Disorders • Epilepsy • Gene Therapies • Mental Retardation • Psychiatry • Renal Disease • CYP3A4 • CYP3A5

Early use of Cenobamate in a case of Non-Convulsive Status Epilepticus in a woman with Progressive Multifocal Leukoencephalopathy (EAN 2026) - " A 54-year-old woman with multiple sclerosis received natalizumab until she was diagnosed with progressive multifocal leukoencephalopathy (mRS4)...FIGURE 3 Follow-up EEG during treatment with levetiracetam, lacosamide, perampanel, and cenobamate... Currently, it is not possible to recommend the use of cenobamate in NCSE, as only anecdotal cases have been reported to date. An important limitation is its slow titration, but it can be considered as a third-line therapy in selected cases with subtle clinical manifestations. Furthermore, CNB may modulate the GABAergic dysfunction described in NCSE."

Clinical • CNS Disorders • Epilepsy • Multiple Sclerosis • Rare Diseases

Antiseizure medication dosing and monitoring in the intensive care unit: a practical narrative review. (PubMed, Intensive Care Med) - "The use of ASMs in the ICU require a distinct approach from outpatient settings. Severity of illness, organ dysfunction and replacement devices, and frequent drug-drug interactions warrant tailored agent selection, dosing, and monitoring."

Journal • Review • CNS Disorders • Critical care • Epilepsy

Neurologists' Views on the Management of Uncontrolled Epilepsy in Spain: A Preliminary Survey. (PubMed, Neurol Ther) - "There is a discrepancy between neurologists' treatment goals and their acceptance of persistent seizures in Spanish neurological practice. Several factors may be limiting the achievement of early seizure freedom, including short patient consultations and a lack of familiarity with new treatments, especially among epilepsy non-specialists. Addressing these barriers could improve outcomes for people with uncontrolled epilepsy."

Journal • CNS Disorders • Epilepsy