Managing epilepsy in the context of intellectual disability can be complicated as this population is known to have higher rates of drug resistance and sensitivity to side effects of antiseizure medications (ASMs). Perampanel is a novel ASM recently approved as an adjunctive treatment for drug resistant focal seizures. It carries a black-box warning for serious psychiatric and behavioral adverse reactions of aggression, irritability, et cetera. However, psychosis is a seldom reported side effect of perampanel. We herein describe a case of a 15-year-old girl with moderate intellectual disability who presented with refractory seizures managed successfully after using perampanel. Around 2 months later, she developed psychosis and aggression. The patient\'s history lacked any significant family or personal history of mental illness. Managing psychotic symptoms was difficult in this case; as perampanel was needed for proper seizure control, and both psychosis and seizures were severe and significantly endangering the patient and people around her. Thus, symptoms were addressed by adding a low-dose risperidone, an atypical antipsychotic. This paper highlights the importance of pre-treatment counselling and monitoring for the emergence of psychiatric side effects including the rarely occurring psychosis while using perampanel, particularly in highly sensitive patients, e.g., those with intellectual disability. We also emphasize on the importance of accurate weighing of risks and benefits while managing psychosis as an adverse event to ASMs in the background of drug-resistant epilepsy.

Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post-dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. PLAIN LANGUAGE SUMMARY: Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications.

Perampanel (PER) is an antiseizure medication (ASM) with a unique mechanism of action, which was approved in Japan for use in combination therapy in 2016 and as a monotherapy in 2020. It has exerted antitumor effects against several types of tumors in vitro. However, the efficacy of PER monotherapy for seizure control is not well-established in patients with brain tumor. In the present study, 25 patients with brain tumor treated using PER monotherapy at our institution were analyzed and compared with 45 patients treated using the most commonly prescribed ASM, levetiracetam (LEV). The PER group was younger and had a higher frequency of glioma cases. During drug administration, seizures were observed in two patients from the PER group (8.0%) and five patients from the LEV group (11.1%); however, the difference was not significant. The incidence of adverse effects did not significantly differ between the groups (12.0 and 2.2%, respectively). In the PER group, mild liver dysfunction was observed in two patients and drug rash in one. In the LEV group, a drug-induced rash was observed in one patient. PER monotherapy may be safe and effective for seizure treatment or prophylaxis in patients with brain tumor. Further large-scale clinical studies are warranted.

ELEVATE (Study 410; NCT03288129) is the first prospective, multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with focal-onset seizures or generalized tonic-clonic seizures in the United States. The study included Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration, perampanel was initiated at 2 mg/day and up-titrated to 4 mg/day at Week 3. Depending on response and tolerability, optional up-titrations to a maximum of 12 mg/day occurred. The primary endpoint was retention rate; additional endpoints included seizure-freedom rate, 50% responder rate, and incidence of treatment-emergent adverse events (TEAEs). At baseline, 10 (18.5%) patients were assigned to the monotherapy group and 44 (81.5%) patients to the first adjunctive therapy group. However, due to the addition of an anti-seizure medication along with perampanel on the first day of treatment, one patient was excluded from the monotherapy subgroup analyses. The mean perampanel exposure duration was 39.8 weeks and 32 (59.3%) patients completed the study. Retention rate at 12 months (or study completion) was 63.0% (monotherapy, 77.8%; first adjunctive therapy, 59.1%). Seizure-freedom rate during the Maintenance Period was 32.7% (monotherapy, 44.4%; first adjunctive therapy, 29.5%) and the 50% responder rate was 78.7% (monotherapy, 85.7%; first adjunctive therapy, 76.9%). TEAEs and serious TEAEs were reported by 88.9% (n = 48/54) and 7.4% (n = 4/54) of patients, respectively. Overall, the efficacy and safety of perampanel as monotherapy or first adjunctive therapy support the use of perampanel as early-line treatment for epilepsy.

We report a case involving a 31-year-old male without any known precipitating injuries presenting with involuntary finger movements and rare seizures. There was a noted family history of tremulous movements. Yet the characteristics of his finger movements were irregular and not typical of essential tremor (ET). Electrophysiological examinations, including video EEG, showed no epileptic discharges, and brain MRI results were normal. However, somatosensory evoked potentials (SEP) revealed the presence of giant SEP, and a positive cortical (C)-reflex was observed, leading to a clinical diagnosis of benign adult familial myoclonus epilepsy (BAFME). Management with valproic acid and perampanel resulted in a significant reduction of symptoms. This case highlights the necessity of considering BAFME in the differential diagnosis for atypical tremorous finger movements, especially with a relevant family history, and the critical role of electrophysiological findings indicative of cortical hyperexcitability.

UNASSIGNED: This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE).
UNASSIGNED: A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction.
UNASSIGNED: In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel.
UNASSIGNED: This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.

UNASSIGNED: There is currently a lack of studies examining the long-term therapeutic effectiveness of the third-generation anti-sezure medication, perampanel (PER), for focal-onset seizures (FOS), particularly in Chinese patients with sleep-related epilepsy (SRE). Additionally, the appropriate dosage, plasma concentration, and the relationship between dose and plasma concentration of PER in Chinese patients are still uncertain.
UNASSIGNED: A prospective, single-center, 24-month observational study was conducted in patients diagnosed with FOS, with a focus on patients with SRE. Changes in seizure frequency from baseline, adverse events, and retention rates were analyzed at 12 and 24 months following the start of the treatment. Tolerability was evaluated based on adverse events and discontinuation profiles. PER plasma concentrations were used to assess dose-concentration-response relationships.
UNASSIGNED: A total of 175 patients were included (median age: 25 years; range: 4-72 years; 53. 1% males and 46.9% females), with the SRE population accounting for 49. 1% (n = 86). The patients diagnosed with SRE showed considerably higher response rates than those who did not have this diagnosis (p = 0.025, odds ratio = 3.8). Additionally, the SRE group adhered better to PER treatment (r = 0.0009). Patients with a shorter duration of epilepsy (median: 3 years; range:2-7 years) demonstrated a more favorable therapeutic response to PER (p = 0.032). Throughout the administration of maintenance doses, among the entire FOS population, the concentration of PER (C0) ranged between 101.5 and 917.4 ng/mL (median, 232.0 ng/mL), and the mean plasma concentration of PER in the responders was 292.8 ng/mL. We revealed a linear relationship between PER dose and plasma concentration, regardless of whether PER was used as monotherapy or add-on therapy. The retention rates were 77.7% and 65. 1% at 12 and 24 months, respectively. Drug-related adverse events occurred in 45.0% of the patients and were mostly manageable.
UNASSIGNED: PER effectively reduced seizure frequency in Chinese patients with FOS, particularly in those with SRE, over a 24-month period. The treatment was well-tolerated and had a clear linear dose-plasma concentration relationship.

UNASSIGNED: Since 2019, Perampanel (PER) has been endorsed in China as an adjunctive treatment for focal seizures, both with and without impaired awareness, and for the transition from focal to bilateral tonic-clonic seizures. Limited research exists regarding the efficacy of PER in treating post-stroke epilepsy (PSE) in China. Empirical studies are essential to guide treatment protocols. We conducted a retrospective study to assess the efficacy and tolerability of PER in 58 PSE patients treated between October 2019 and July 2023.
UNASSIGNED: This study encompassed 58 patients with PSE, treated with PER either as monotherapy or as part of adjunctive therapy, and underwent follow-up for a minimum duration of 6 months. The study assessed changes in seizure frequency, adverse events (AEs), drug retention rate, maintenance dose, and adverse reactions following PER treatment.
UNASSIGNED: The study included 58 PSE patients, with 60.3% males and 39.7% females, ranging in age from 18 to 89, mostly within the 61-70 age group. Ischemic strokes constituted 58.6% of cases, while hemorrhagic strokes accounted for 41.4%. Focal seizures, either with or without impaired awareness, were noted in 62.1% of patients, and a transition from focal to bilateral tonic-clonic seizures was seen in 32.8%. The retention rates for PER at 3 and 6 months stood at 94.8% and 84.5% respectively, and the most commonly administered maintenance dose was 4 mg/day (41.28%). In the adjunctive therapy group, efficacy rates were 66.7% at 3 months and 78.6% at 6 months, compared to 80.0% at 3 months and 85.7% at 6 months in the monotherapy group. In the efficacy analysis, with a criterion of ≥50% reduction in seizure frequency, the overall efficacy rates at 3 and 6 months were 69.1% and 79.6%, respectively. Adverse reactions occurred in 46.6% of patients, primarily involving irritability and somnolence (both 27.6%), with no marked difference in incidence between the adjunctive and monotherapy groups (P > 0.05).
UNASSIGNED: PER exhibits favorable efficacy and tolerability in Chinese PSE patients, possibly at lower doses.

UNASSIGNED: Antiseizure medications (ASMs) are first line therapy for seizure disorders. Their effects on arrhythmias, especially the risk of arrhythmias associated with lacosamide (LCM), levetiracetam (LEV), and perampanel (PER), have been intensely investigated.
UNASSIGNED: We searched four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) until August 6, 2023. We used a common effects model and reported data as pooled incidence with 95% CIs. Meta-analyses were conducted to elucidate the risk of arrhythmias with different drugs, and Egger\'s regression was performed to detect publication bias analysis.
UNASSIGNED: We included 11 clinical trials with 1,031 participants. The pooled incidence of arrhythmias in the LEV group was 0.005 (95% CI: 0.001-0.013), while it was 0.014 in the LCM group (95% CI: 0.003-0.030). Publication bias analyses indicated no significant bias in the LEV group (t = 0.02, df = 4, p-value = 0.9852) but a significant bias in the LCM group (t = 5.94, df = 3, p-value = 0.0095). We corrected for this bias in the LCM group using the trim-and-fill method, which yielded a similar pooled incidence of 0.0137 (95% CI: 0.0036-0.0280), indicating good reliability. Due to insufficient studies, we could not conduct a meta-analysis for PER, and we analyzed them in our systematic review.
UNASSIGNED: The use of LCM significantly elevated the risk of arrhythmias, while LEV had non-significant arrhythmogenic effects. As for the arrhythmogenic effects of PER, more clinical trials are needed in the future.

UNASSIGNED: To investigate whether there exists a statistically significant distinction between the effectiveness and tolerance of perampanel (PER) and the number of antiseizure medications (ASMs) that were tried prior to administering PER.
UNASSIGNED: A prospective, observational study was performed at West China Hospital of Sichuan University. The study included patients diagnosed with epilepsy who were prescribed PER and were monitored for a minimum of 6 months. The efficacy of PER was evaluated at 1, 3, 6, and 12-month intervals by examining the retention rate and the 50% response rate. All statistical analyses were conducted using IBM SPSS Statistics version 25 (IBM Corporation, Armonk, New York).
UNASSIGNED: A total of 1,025 patients were identified, of which 836 were included in the analysis. Seven hundred and eighty-nine patients (94.4%) were followed up for a year. The median age of the patients was 29.32 ± 14.06 years, with 45.81% of the patients being male and 17.0% being adolescents. The average duration of epilepsy was 11.22 ± 8.93 years. Overall, PER was discontinued in 49.5% of patients, with the most common reasons being inadequate therapeutic effect and treatment-emergent adverse events (TEAEs). At the 6-month follow-up, the retention rate was 54.2% (454/836), and 39.6% of patients had a 50% response. At the 12-month follow-up, the retention rate was 49.4% (340/789), and 44.5% of patients had a 50% response. Patients who received PER as monotherapy had the highest retention rates (P = 0.034) and 50% response rates (P < 0.001) at any follow-up point. TEAEs were reported in 32.0% of patients, and these led to discontinuation in 15.4% of patients. The most common TEAEs were dizziness and somnolence. There was no significant difference between subgroups (P = 0.57), but there was a significant difference between the dosage of PER and TEAEs (P < 0.001).
UNASSIGNED: The study concludes that PER is effective in treating both focal and generalized tonic-clonic seizures. Patients who had fewer previous exposures to ASMs exhibited higher response rates to PER. TEAEs related to PER dosage were more prevalent during the first 3 months of treatment and tended to improve with continued use, ultimately demonstrating favorable long-term tolerability.