Perampanel for the treatment of people with idiopathic generalized epilepsy in clinical practice.

OBJECTIVE: This study was undertaken to evaluate perampanel (PER) when used under real-world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. METHODS: The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic-clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation. RESULTS: The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months. SIGNIFICANCE: This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad-spectrum antiseizure medication for the treatment of IGE.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice.

The PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 5193 PWE. Retention, effectiveness and safety/tolerability were assessed in 4721, 4392 and 4617, respectively. Retention on PER treatment at 3, 6, and 12 months was 90.5%, 79.8%, and 64.2%, respectively. Mean retention time on PER treatment was 10.8 months. The 50% responder rate was 58.3% at 12 months and 50.0% at the last visit, and the corresponding seizure freedom rates were 23.2% and 20.5%, respectively; 52.7% of PWE with status epilepticus responded to PER treatment. Overall, 49.9% of PWE reported AEs and the most frequently reported AEs (≥ 5% of PWE) were dizziness/vertigo (15.2%), somnolence (10.6%), irritability (8.4%), and behavioral disorders (5.4%). At 12 months, 17.6% of PWEs had discontinued due to AEs. PERMIT demonstrated that PER is effective and generally well tolerated when used to treat people with focal and/or generalized epilepsy in everyday clinical practice.

Differences in aggression as psychiatric side effect of levetiracetam and perampanel in patients with epilepsy.

PURPOSE: Aggression is the most commonly encountered antiepileptic-drug (AED)-induced psychiatric adverse effects. Levetiracetam (LEV) is well known to be associated with increased rates of aggression, while perampanel (PER) is also recognized as a potentially aggression-promoting agent, though opinions vary. However, few studies have addressed questions regarding whether the nature of irritability-aggression differs between those drugs. The present study used a standardized rating scale to examine aggression among patient with epilepsy who received LEV or PER using specific measures to confirm the effects of the drugs. METHODS: We enrolled 144 consecutive outpatients receiving treatment for epilepsy with LEV (n = 103) or PER (n = 41), and determined their effects regarding aggression using the Buss-Perry Aggression Questionnaire (BAQ). For analysis, total BAQ scores for the LEV and PER subjects were compared to determine whether the aggression-promoting effects of the agents differed, and which BAQ subdomains (physical aggression, verbal aggression, anger, hostility) were related to production of aggression in patients taking either LEV or PER. As a subsidiary analysis, clinical variables inclusive of administered AED type that showed a significant impact on BAQ scores were determined. RESULTS: The LEV group had a significantly higher hostility score (19.4 ±â€¯5.8) as compared to the PER group (17.2 ±â€¯6.3) in subscale analysis (p < 0.05). In multiple regression analysis, LEV had a significant association with higher hostility score (P = 0.006). CONCLUSION: Our results indicate that while easily visible outward-directed aggression tends to be dominant in patients given PER, aggression provoked by LEV may be felt more subjectively or in an inward-directed manner, which can lead to more diverse expression and misrecognition.

Aggression as psychiatric side effect of newer AEDs in patients with epilepsy: Cross-sectional study based on Buss-Perry Aggression Questionnaire.

PURPOSE: Aggression-irritability is the most commonly encountered antiepileptic-drug-induced psychiatric adverse effects. In this cross-sectional study, we tried to assess antiepileptic-drug-induced aggression in patients with epilepsy (PWE) with a standardized rating scale. METHODS: Two hundred sixty-six consecutive outpatients receiving treatment for epilepsy with antiepileptic drugs (AEDs) were initially examined, and the effects of the investigated drugs in regard to aggression were investigated using the Buss-Perry Aggression Questionnaire (BAQ). We compared BAQ scores as a function of a specific class of AEDs, levetiracetam (LEV), lacosamaide (LCM), perampanel (PER), and carbamazepine (CBZ), and determined whether AED type had a relationship with aggression. Additionally, the association of BAQ score with other clinico-demographic variables was also assessed. RESULTS: One-way ANOVA revealed that the LEV group had a significantly higher mean BAQ score as compared to the CBZ (P = 0.001) and LCM (P = 0.029) groups for total score. In subscale analysis, the LEV group had higher scores than the CBZ group for the physical aggression (p = 0.01), verbal aggression (p = 0.02) and hostility (p = 0.01) subscales, while the LEV group had a significantly higher mean score than the LCM group for hostility (p = 0.025). In multiple regression analysis, LEV had a statistically significant impact on increased total BAQ score (B = 0.119, p = 0.049). In contrast, CBZ (B = -0.191, p = 0.002), older age at epilepsy onset (B = -0.269, p = 0.000) and female gender (B = -0.210, p = 0.000) had a significant association with lower total BAQ score. CONCLUSIONS: Our results indicate that LEV is associated with increased aggression, while CBZ and LCM showed effects to reduce aggression.

The effect of perampanel on aggression and depression in patients with epilepsy: A short-term prospective study.

PURPOSE: Using specialized tools, we assessed patients receiving perampanel (PER) to investigate its effects on aggression and depression, as well as the impact of other concomitant antiepileptic drugs (AEDs) on those conditions. METHOD: Seventy-seven patients with epilepsy were initially enrolled, then examined at entry and 12 weeks later (endpoint). At both examinations, assessments were performed with the Buss Perry Aggression Questionnaire (BAQ) and Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). Ultimately, 59 patients completed the study. RESULTS: Total BAQ (p = 0.013) and NDDI-E (p = 0.000) scores at the endpoint were significantly increased in comparison with those at entry. Analysis with 4 subscales showed increases in both verbal and physical aggression, while multivariate analysis revealed that concomitant AED administration did not have a significant impact on the increase of BAQ or NDDI-E score. A dose-dependent effect of PER was confirmed in BAQ, but not NDDI-E results. PER was discontinued due to adverse psychiatric effects in 3.9% of the patients. CONCLUSIONS: The present findings indicate that PER increases assessment scores indicative of aggression as well as depression. No additional aggression-augmenting effect was seen with concomitant AED administration.

Pre- and post-surgical psychiatric assessments and intervention by major epilepsy centers in Japan - Nationwide survey.

BACKGROUND: Although psychiatric issues following epilepsy surgery are now widely recognized as a major problem, actual awareness of these issues by epilepsy centers remains to be elucidated. This is the first known report regarding the use of psychiatric assessments and interventions by epilepsy centers throughout Japan. PARTICIPANTS AND METHODS: At the beginning of 2016, we sent a questionnaire regarding psychiatric assessments performed before and after epilepsy surgery, psychiatric intervention after surgery, and future plans for dealing with psychiatric issues in relation to epilepsy surgery, which consisted of a total of 24 items, to all members of the Japan Epilepsy Center Association (JEPICA). Nearly all major epilepsy centers in Japan are included in JEPICA, which had 31 members in 2016. Twenty-four (77%) of the 31 centers responded to the questionnaire. RESULTS: Seventeen (70.8%) centers answered that a psychiatrist was incorporated as part of their epilepsy surgery unit. In addition, 17 (70.8%) noted that psychiatric assessments were obtained prior to surgery, which were performed by psychiatrists in 8 (33.3%) centers and psychologists in 11 (45.8%). In 23 (95.8%) of the centers, the risk of occurrence of psychiatric illness following surgery was routinely explained prior to surgery, at least to surgical candidates with high susceptibility. In total, cases of psychiatric illness following surgery had been experienced in 16 (66.7%) centers, with depression as the most commonly encountered (41.7%), followed by anxiety (33.3%), psychosis (25.0%), and psychogenic non-epileptic seizures (8.3%). DISCUSSION: Strong points of epilepsy centers in Japan include serious concern regarding post-surgical psychiatric illness by nearly all members of JEPICA and explanation of the risk of psychiatric adverse events provided beforehand to their patients. On the other hand, the small size of some epilepsy centers, along with lack of a standardized method for evaluation of psychiatric symptoms as well as dependence on the individual willingness of psychiatrists assigned as members of the epilepsy units, seem to have led to significant diagnostic and therapeutic gaps among epilepsy centers regarding psychiatric issues related to epilepsy surgery.

Psychogenic non-epileptic seizure in patients with intellectual disability with special focus on choice of therapeutic intervention.

PURPOSE: There have been a number of studies exploring treatments for psychogenic non-epileptic seizure (PNES) but largely neglecting the sizable subgroup of patients with intellectual disability (ID). In the present study, we attempted to demonstrate effects and preferred modes of therapeutic intervention in PNES patients with ID being treated at a Japanese municipal center with a short referral chain. METHODS: We examined 46 PNES patients with ID (ID group) and 106 PNES patients without ID (non-ID group) retrospectively in case charts. In addition to examining basic demographic and clinical data, effects of different therapeutic intervention were examined as a function of decrease or disappearance of PNES attacks in the ID group. RESULTS: Age at the first visit as well as PNES onset was younger in the ID than in the non-ID group (t=2.651, p=0.009; t=3.528, p=0.001, respectively). PNES-free ratio at the last visit tended to be higher in the non-ID group (chi square=3.455; p=0.063). Psychosis was more often encountered in the ID group (chi square=13.443; p=0.001). Although cognitive therapy and pharmaco-therapeutic approaches were quite similarly distributed in both groups, environmental adjustment was often introduced in the ID group (44%) as compared to the non-ID group (15%) (chi square=14.299; p=0.001). Brief weekly visit service is also more often utilized by the patients with ID (54%) than by those without ID (35%) (chi square=5.021, p=0.025). CONCLUSIONS: Optimal treatment approaches in this sizable patient subgroup should be the subject of future prospective studies.

Delusional experience awareness gap between patients and treating doctors - Self-reported EPDS questionnaire.

OBJECTIVES: Although early and rapid recognition of a psychotic trend in patients with epilepsy certainly pay dividends, there is no handy assessment instrument for screening because of multiple intrinsic difficulties such as lack of a standard screener as well as a reliability gap for screeners between help-seeking and general populations. On the other hand, the predominance of positive symptoms at the initial stage of psychosis is a promising aspect of this specific group. The following specific questions were examined. Is there a measurable difference between the assessment of the treating doctor and the real feelings of the patient? How well does the attained score correspond to the clinical diagnosis? METHODS: The self-reported Emotions with Persecutory Delusions Scale (EPDS) questionnaire, previously validated in a general population, was used as the assessment tool for psychotic trend in 79 outpatients with epilepsy. Independent from scoring by the patients, the treating doctors also expressed their impressions about the same patients using the same scoring tool. RESULTS: Stepwise multiple regression analysis of the EPDS scores of both doctors and patients revealed that a clinical diagnosis of psychosis was the only independent variable significantly related to EPDS score. Also, there was a significant difference between the EPDS scores of the patients and those of the doctors, in favor of the former. SIGNIFICANCE: Clinical diagnosis of psychosis proved to be the most powerful determinant of EPDS score independent from other clinical factors. The awareness gap between doctors and patients based on EPDS score revealed that treating doctors often clearly underestimate the psychotic trend of their patients. Our findings suggest that such simple tests as EPDS, with a narrow focus on attenuated delusional symptoms, may help screen for an early psychotic episode in patients with epilepsy that may otherwise not be diagnosed by their physicians.