pISSN 1738-6586   eISSN 2005-5013
Open Access, Peer-reviewed
    J Clin Neurol. 2023 Jul;19(4):358-364. English.
    Published online Apr 18, 2023.
    https://doi.org/10.3988/jcn.2022.0338
    Copyright © 2023 Korean Neurological Association
    Original Article

    Five-Year Retention of Perampanel and Polytherapy Patterns: 328 Patients From a Single Center in South Korea

    Kyung-Il Park,a,b Sungeun Hwang,c Hyoshin Son,d Kon Chu,a,d Ki-Young Jung,a,d and Sang Kun Leea,d
      • aDepartment of Neurology, Seoul National University College of Medicine, Seoul, Korea.
      • bDivision of Neurology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
      • cDepartment of Neurology, Ewha Womans University Mokdong Hospital, Seoul, Korea.
      • dDepartment of Neurology, Seoul National University Hospital, Seoul, Korea.
    • Correspondence: Sang Kun Lee, MD, PhD. Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. Tel +82-2-2072-2923, Fax +82-2-3072-4949, Email: sangun2923@gmail.com
    Received September 07, 2022; Revised November 16, 2022; Accepted November 18, 2022.

    This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Abstract

    Background and Purpose

    Perampanel (PER) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist used to treat focal and generalized epilepsy. Comprehensive data from real-world settings with long-term follow-ups are still scarce. This study aimed to determine the factors related to PER retention and the polytherapy pattern with PER.

    Methods

    We reviewed all patients with epilepsy with a history of PER prescription during 2008–2017 and over a follow-up of >3 years. PER usage patterns and associated factors were analyzed.

    Results

    Among the 2,655 patients in the cohort, 328 (150 females, 178 males) were enrolled. The ages at onset and diagnosis were 21.1±14.7 years and 25.6±16.1 years (mean±standard deviation), respectively. The age at the first visit to our center was 31.8±13.8 years. Seizure types were focal, generalized, and unknown onset in 83.8%, 15.9%, and 0.3% of patients, respectively. The most common etiology was structural (n=109, 33.2%). The maintenance duration of PER was 22.6±19.2 months (range=1–66 months). The initial number of concomitant antiseizure medications was 2.4±1.4 (range=0–9). The most common regimen was PER plus levetiracetam (n=41, 12.5%). The median number of 1-year seizures before PER usage was 8 (range=0–1,400). A seizure reduction of >50% was recorded in 34.7% of patients (52.0% and 29.2% in generalized and focal seizures, respectively). The 1-, 2-, 3-, 4-, and 5-year retention rates for PER were 65.3%, 50.4%, 40.4%, 35.3%, and 21.5%, respectively. A multivariate analysis indicated that lower age at onset was associated with longer retention (p=0.01).

    Conclusions

    PER was safely used in patients with diverse characteristics and was maintained for a long time in a real-world setting, especially in patients with a lower age at onset.

    Keywords
    perampanel; retention; long-term; real-world; polytherapy

    INTRODUCTION

    Epilepsy is a burdensome disease that has the fourth-highest disability-adjusted life years.1 More than 20 antiseizure medications (ASMs) with diverse modes of action2 have been developed and approved for treating focal and generalized epilepsy. The effectiveness of these various medications has been less than ideal, given that epilepsy is still medically intractable in about 30% of affected patients.3 Among these drugs, perampanel (PER) has a peculiar mechanism that targets postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and is approved worldwide as an adjunctive or monotherapy for focal and primary generalized tonic–clonic seizures.

    Randomized controlled studies have demonstrated the effectiveness of PER in focal and generalized epilepsy by comparing it with placebo groups.4, 5, 6, 7 However, these studies did not ensure their efficacy in real-world circumstances due to their inflexible designs. Accordingly, several real-world observational studies8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 have been conducted in various countries, but studies with sufficiently long observation periods are still lacking.

    In the current study, we aimed to establish the real-world outcome data for PER from a single institution using a relatively large population and long-term observation period, and determine the factors related with PER retention.

    METHODS

    Data collection

    We initially established a retrospective cohort that comprised 2,655 adult patients with epilepsy. The inclusion criteria were as follows: patients with 1) a first visit to our department during 2008–2017, 2) an epilepsy diagnosis using the International League Against Epilepsy (ILAE) definition, 3) more than 3 years of follow-up data, and 4) more than 3 months of treatment using antiepileptic drugs.

    Based on this cohort, we selected all patients with a history of PER prescription. We reviewed all medical records that described seizure occurrence, age at onset, number/name of ASM prescribed, and follow-up duration. The seizure type, epilepsy classification, and etiology were determined through the consensus of three experienced epileptologists (K.I Park, S Hwang, and S.K Lee). The main outcome was maintenance duration, which was defined as the duration of PER treatment.

    This study was approved by the Seoul National University Hospital Institutional Review Board and followed the principles of the Declaration of Helsinki. The need to obtain written consents was waived due to the retrospective design (IRB No. H-2102-178-1200).

    Statistical analysis

    The numerical values are expressed as mean±standard deviation or number (percentage) values. Student’s t-test and ANOVA were used to compare continuous variables. Correlations are quantified using Pearson coefficients. To ensure the independent factor of PER maintenance, we performed multiple linear regression analyses that included variables with significance in the univariate analysis and other potentially meaningful variables. Significance was set as a two-tailed probability value of p<0.05. SPSS (version 25, IBM Corp., Armonk, NY, USA) and GraphPad Prism (version 9, Dotmatics, San Diego, CA, USA) were used for all statistical analyses.

    RESULTS

    Among the 2,655 patients in the cohort, 328 (150 females, 178 males) were found to have a history of PER prescription and included in the analyses. The ages at seizure onset and at diagnosis were 21.1±14.7 years and 25.6±16.1 years (mean±standard deviation), respectively. The age at the first visit to our center was 31.8±13.8 years. According to the revised classification of seizure types defined by the ILAE in 2017,24 focal, generalized, and unknown onset accounted for 83.8%, 15.9%, and 0.3% of the enrolled patients, respectively. Structural etiology was the most common (n=109, 33.2%). The median number of 1-year seizures before PER usage was 8 (range=0–1,400).

    The total maintenance duration of PER was 22.6±19.2 months (range=1–66 months). The entire follow-up duration was 94.3±32.6 months. There was no correlation between the entire follow-up and PER maintenance duration (r=0.24, p=0.67). The characteristics of the included patients are summarized in Table 1.

    Table 1
    Descriptive data of the study population

    PER retention and its associated factors

    For the analysis of maintenance, we excluded three patients with a loss of follow-up data immediately after being prescribed PER. Overall, the retention rate decreased by approximately 10% each year. The proportions of 1-, 2-, 3-, 4-, and 5-year retention of PER were 65.3%, 50.4%, 40.4%, 35.3%, and 21.5%, respectively (Fig. 1A). In terms of efficacy, the responder rate (>50% seizure reduction) was achieved in 34.7% of patients,including 12.5% of whom had complete seizure freedom. The responder rates of generalized and focal epilepsy were 52.0% and 29.2%, respectively. Dropout due to drug-related adverse events occurred in 9.1% of patients (n=30). The most common adverse reaction was somnolence (40.0%), followed by psychiatric symptoms (26.7%) such as aggression, suicidal ideas, and anxiety.

    Fig. 1
    Long-term outcome of PER. A: The proportion of cases with PER retention decreased by approximately 10% each year over 5 years. B: Kaplan–Meier curve demonstrating the longitudinal difference between the maintenance in focal and generalized seizures. C–E: PER maintenance duration was longer in generalized than in focal seizures. The numbers of ASMs and seizure frequency before PER did not differ between the two seizure types. *p<0.05. ASM, antiseizure medication; PER, perampanel; 1-yr sz, seizures during 1 year.

    The univariate analysis demonstrated that seizure type and epilepsy classification were varied significantly with the PER maintenance duration (p=0.007 and p=0.018, respectively; Table 2). We found a negative association between age and PER maintenance duration (r=-0.167, p=0.03). There were no significant associations among or differences between other variables, such as sex, seizure frequency before PER initiation, follow-up duration, febrile seizure, family history of epilepsy, or the number of ASMs before PER prescription.

    Table 2
    Factors related to PER maintenance duration

    In comparing seizure types, PER maintenance duration was longer in generalized than in focal seizures (28.71±19.58 months vs. 21.25±18.86 months; Fig. 1B and C). However, the numbers of ASMs and seizures before PER did not differ (Fig. 1D, E, and Table 3). Age at epilepsy onset was lower in generalized than in focal seizures (22.23±15.40 years vs. 15.47±8.65 years, p<0.01).

    Table 3
    Differences between seizure types

    However, in the multivariate analysis, only age at onset (p=0.01) remained as a factor significantly associated with PER maintenance duration (Table 4 and Fig. 2A). The adjusted R2 value, p-value, and Durbin-Watson statistic of the regression model were 0.03, 0.04, and 1.95, respectively. According to the etiological classification of epilepsy, PER was seemingly maintained more in genetic or infectious etiologies than in structural or immune etiologies at the 3-year follow-up (Fig. 2B).

    Fig. 2
    Maintenance of PER. A: PER maintenance duration was negatively associated with age at epilepsy onset. B: Kaplan–Meier curve demonstrating the pattern of PER maintenance according to epilepsy etiology. PER, perampanel.

    Table 4
    Multiple linear regression results for factors related to PER maintenance

    Combination of ASMs

    The initial number of concomitant ASMs was 2.4±1.4 (range=0–9). The most common initial concomitant ASM with PER as dual therapy was levetiracetam (LEV; n=41, 51.2%), followed by oxcarbazepine (n=15, 18.8%), zonisamide (n=7, 8.8%), and valproate (n=6, 7.5%). The most common initial concomitant ASM regimen with PER as a triple therapy was LEV plus oxcarbazepine (n=22, 22.7%) followed by LEV plus valproate (n=13, 13.4%). The most common quadruple-therapy combination including PER was clobazam plus LEV plus oxcarbazepine (n=8, 12.3%).

    The various combinations administered alongside PER are listed in Supplementary Tables 1, 2, 3 (in the online-only Data Supplement). We further compared the PER-plus-LEV regimen (the most common dual combination) with regimens involving PER plus other than drugs. The PER-plus-LEV regimen was more commonly prescribed to females (p=0.045), while other variables did not differ with sex, such as PER responders, age at onset, age at diagnosis, seizure classification, epilepsy classification, maintenance duration, follow-up duration, the number of ASMs before PER usage, and seizure frequency before PER (Supplementary Table 4 in the online-only Data Supplement).

    Additionally, in the subset of dual therapies that included PER, we divided patients into two groups according to the presence of sodium-channel blockers. The proportion of responders did not differ significantly (p=0.59) irrespective of the concomitant sodium-channel blockers in either generalized (p=0.11) or focal (p=0.33) epilepsy.

    DISCUSSION

    This study has revealed the real-world circumstances of PER prescription in a single center in South Korea and attempted to determine the associated factors that influence PER maintenance without any support from pharmaceutical companies.

    Retrospective observational studies attain higher efficacy compared with pivotal trials because of the lower seizure burden observed in real-world population studies. A study that included 98 patients with focal- or generalized-onset seizures observed an 80.9% 1-year retention rate of PER monotherapy. It found a 52.8% responder rate and 41.5% seizure remission rate at a 1-year follow-up.25 In another study26 performed on an Asian population found a seizure-freedom rate in focal-onset seizures during a 26-week maintenance period of 63%–74%, depending on the dosage. A German and Austrian study observed a 60% 6-month retention rate.8 Our 1-year retention rate of 65.3% was therefore comparable with the results of previous studies.

    The univariate analysis performed in the current study indicated that PER maintenance duration was associated with seizure type. PER was more effective in generalized than in focal epilepsy, a finding that is common in both randomized and real-world observation settings,15 although some studies have found similar efficacies for PER between generalized and focal seizures, and bilateral tonic–clonic seizures.27 A review article28 that summarized four randomized controlled studies reported that PER had better efficacy in generalized than in focal epilepsy. The responder rate in focal epilepsy changed from 28.5% to 35.3% after using PER (vs. 19.3% with placebo). However, generalized epilepsy was found to have a much higher responder rate of 64.2% (vs. 39.5% with placebo). The high responder rate of placebos in this study is still under debate.

    Early epilepsy onset was the only independent variable of PER maintenance in the current study, with PER being maintained for longer when seizures started earlier. Regarding efficacy, a previous study demonstrated that old age was related to seizure freedom.10 Additionally, in a pooled analysis of 2,396 European patients,14 higher age at PER initiation was associated with seizure freedom. Another study involving older patients (>65 years old) found that the response, seizure freedom, and retention rates at 12 months were 57.6%, 23.9%, and 47.8%, respectively.18 While the efficacy was better for a higher age, the retention rate did not differ significantly with age. Another study also supported that old age is related to an increased seizure-freedom rate.19 Adverse events were observed in nearly 80% of old adults in a pooled analysis,14 which was much higher than observations in other previous observational studies. Considering that retention implies high efficacy and safety, more adverse events in old age could explain the shorter maintenance duration in that study. This explanation was clearly supported by the finding of one recent Japanese study20 that compared retention rates between patients older and younger than 65 years. The seizure outcome was better in older patients and the retention rate at 52 weeks was higher in younger patients (59.7% vs. 53.3%), which was consistent with our results. A recent study with a comparison age cutoff of 18 years also found a similar retention rate pattern, with 2-year retention rates of 53.5% and 47.8% in adolescents and adults, respectively.29

    The current study found that the retention rates were 196/300 (65.3%), 128/254 (50.4%), 80/198 (40.4%), 54/153 (35.3%), and 14/65 (21.5%) at 1-, 2-, 3-, 4-, and 5-year follow-ups, respectively. We suggest that the monotonic decrease in PER retention could be attributed to continued seizure-control efforts despite its partial effect, rather than long-term adverse events such as weight gain. Switching into other ASMs is common in routine practice considering patient’s economic burden.

    Regarding etiology, vascular10 and structural13 causes have been presented as factors associated with good seizure outcomes. However, our study did not demonstrate any difference among various etiologies. The populations of previous studies were relatively small and also comprised small numbers of patients with generalized epilepsy. We found that the retention pattern was similar for structural and unknown etiologies. A novel finding was genetic etiology, which seemed to allow better PER maintenance than immune or structural etiologies, although the difference was not significant.

    The pattern of combination is another issue to discuss. Among 328 patients, 12 (3.7%) underwent monotherapy while the remaining 316 underwent polytherapy. The drug most commonly combined with PER was LEV, and the second most common was oxcarbazepine. Because PER has a peculiar mode of action in targeting AMPA receptors, the conceptually ideal polytherapy combination with PER could be diverse. We additionally compared the most common dual combinations with other combinations to search for differences in efficacy, retention, and other epilepsy variables. However, the only significant difference was the female preponderance in the PER-plus-LEV regimen. In addition, no differences in efficacy were found among drugs combined with PER. While this study has demonstrated the pattern or priority of the selection of ASMs with a focus on PER, more in-depth studies with randomized designs are necessary for performing direct comparisons in the future.

    The main limitation of this study was that the patients had greater burdens of epilepsy and ASMs than those in other studies. Most patients used multiple ASMs, and the number of drugs used before PER initiation was 2.4±1.4. The maximum number of ASMs including PER was as high as 10. Seizure outcome is well known to be determined by the effect of the first or second ASM treatment, and so PER might not have exhibited its full capabilities in our population. However, diverging from studies with randomized or prospective designs, the trends of ASM combinations and seizure outcomes in routine clinical practice provide context to the real world, while other confounders make it difficult to explain the independent effect of PER.

    In conclusion, PER was safely used by various patients and maintained for long durations in a real-world setting, especially in patients who were younger at onset. The efficacy of introducing PER to patients who use multiple drugs should be investigated in the future while considering potential confounders.

    Supplementary Materials

    The online-only Data Supplement is available with this article at https://doi.org/10.3988/jcn.2022.0338.

    Supplementary Table 1

    Duotherapy pattern of PER

    Click here to view.(15K, pdf)

    Supplementary Table 2

    Triple therapy pattern of PER

    Click here to view.(15K, pdf)

    Supplementary Table 3

    Quadruple pattern of PER

    Click here to view.(16K, pdf)

    Supplementary Table 4

    Comparing PER+LEV and PER+others

    Click here to view.(22K, pdf)

    Notes

    Author Contributions:

    • Conceptualization: Kyung-Il Park, Sang Kun Lee.

    • Data curation: Kyung-Il Park, Sungeun Hwang, Ki-Young Jung, Sang Kun Lee.

    • Formal analysis: Kyung-Il Park, Sungeun Hwang, Hyoshin Son, Kon Chu.

    • Investigation: Kyung-Il Park, Sungeun Hwang, Hyoshin Son, Kon Chu.

    • Methodology: Kyung-Il Park, Sungeun Hwang.

    • Supervision: Kon Chu, Ki-Young Jung, Sang Kun Lee.

    • Visualization: Kyung-Il Park.

    • Writing—original draft: Kyung-Il Park.

    • Writing—review & editing: all authors.

    Conflicts of Interest:The authors have no potential conflicts of interest to disclose.

    Funding Statement:This study was funded by Myung-In Pharmaceuticals.

    Availability of Data and Material

    The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

    References

      1. Feigin VL, Vos T, Alahdab F, Amit AML, Bärnighausen TW, Beghi E, et al. GBD 2017 US Neurological Disorders Collaborators. Burden of neurological disorders across the US from 1990-2017: a global burden of disease study. JAMA Neurol 2021;78:165–176.
      1. Kanner AM, Bicchi MM. Antiseizure medications for adults with epilepsy: a review. JAMA 2022;327:1269–1281.
      1. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314–319.
      1. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, et al. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology 2012;79:589–596.
      1. French JA, Krauss GL, Steinhoff BJ, Squillacote D, Yang H, Kumar D, et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305. Epilepsia 2013;54:117–125.
      1. Krauss GL, Serratosa JM, Villanueva V, Endziniene M, Hong Z, French J, et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 2012;78:1408–1415.
      1. French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology 2015;85:950–957.
      1. Steinhoff BJ, Hamer H, Trinka E, Schulze-Bonhage A, Bien C, Mayer T, et al. A multicenter survey of clinical experiences with perampanel in real life in Germany and Austria. Epilepsy Res 2014;108:986–988.
      1. Rohracher A, Kalss G, Leitinger M, Granbichler C, Deak I, Dobesberger J, et al. Two-year real-world experience with perampanel in patients with refractory focal epilepsy: Austrian data. Ther Adv Neurol Disord 2016;9:445–453.
      1. Villanueva V, Garcés M, López-González FJ, Rodriguez-Osorio X, Toledo M, Salas-Puig J, et al. Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: the FYDATA study. Epilepsy Res 2016;126:201–210.
      1. Chiang HI, Lim SN, Hsieh HY, Cheng MY, Chang CW, Johnny Tseng WE, et al. Preliminary Asian experience of using perampanel in clinical practice. Biomed J 2017;40:347–354.
      1. Lin KL, Lin JJ, Chou ML, Hung PC, Hsieh MY, Chou IJ, et al. Efficacy and tolerability of perampanel in children and adolescents with pharmacoresistant epilepsy: the first real-world evaluation in Asian pediatric neurology clinics. Epilepsy Behav 2018;85:188–194.
      1. Morano A, Fattouch J, Albini M, Casciato S, Fanella M, Basili LM, et al. Perampanel as adjunctive therapy in highly refractory epilepsies: real-world data from an Italian tertiary care epilepsy centre. J Neurol Sci 2018;390:67–74.
      1. Rohracher A, Zimmermann G, Villanueva V, Garamendi I, Sander JW, Wehner T, et al. Perampanel in routine clinical use across Europe: pooled, multicenter, observational data. Epilepsia 2018;59:1727–1739.
      1. Villanueva V, Montoya J, Castillo A, Mauri-Llerda JÁ, Giner P, López-González FJ, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: the 12-month GENERAL study. Epilepsia 2018;59:1740–1752.
      1. Chang RS, Lui HKK, Leung YHI, Leung WCY, Yam KK, Wang Y. Efficacy and tolerability of perampanel as an adjunct therapy in refractory epilepsy from real-world experience. J Neurol Sci 2019;405:116416
      1. Abril Jaramillo J, Estévez María JC, Girón Úbeda JM, Vega López Ó, Calzado Rivas ME, Pérez Díaz H, et al. Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON). Epilepsy Behav 2020;102:106655
      1. Lattanzi S, Cagnetti C, Foschi N, Ciuffini R, Osanni E, Chiesa V, et al. Adjunctive perampanel in older patients with epilepsy: a multicenter study of clinical practice. Drugs Aging 2021;38:603–610.
      1. Sagar P, Wawryk O, Vogrin S, Whitham E, Kiley M, Frasca J, et al. Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes. Epilepsy Behav 2021;119:107935
      1. Inoue Y, Sumitomo K, Matsutani K, Ishii M. Evaluation of real-world effectiveness of perampanel in Japanese adults and older adults with epilepsy. Epileptic Disord 2022;24:123–132.
      1. Villanueva V, D’Souza W, Goji H, Kim DW, Liguori C, McMurray R, et al. PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice. J Neurol 2022;269:1957–1977.
      1. Wechsler RT, Wheless J, Zafar M, Huesmann GR, Lancman M, Segal E, et al. PROVE: retrospective, non-interventional, phase IV study of perampanel in real-world clinical care of patients with epilepsy. Epilepsia Open 2022;7:293–305.
      1. Hwang SK, Lee YJ, Nam SO, Kim WS, Kim JS, Kim SJ, et al. Real-life effectiveness and tolerability of perampanel in pediatric patients aged 4 years or older with epilepsy: a Korean national multicenter study. J Clin Neurol 2020;16:53–59.
      1. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology. Epilepsia 2017;58:512–521.
      1. Toledano Delgado R, García-Morales I, Parejo-Carbonell B, Jiménez-Huete A, Herrera-Ramirez D, González-Hernández A, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: experience from a national multicenter registry. Epilepsia 2020;61:1109–1119.
      1. Yamamoto T, Lim SC, Ninomiya H, Kubota Y, Shin WC, Kim DW, et al. Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: the open-label Study 342 (FREEDOM Study). Epilepsia Open 2020;5:274–284.
      1. Nishida T, Lee SK, Wu T, Tiamkao S, Dash A. Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: a comparative study of Asian and non-Asian populations. Epilepsia 2019;60 Suppl 1:47–59.
      1. Potschka H, Trinka E. Perampanel: does it have broad-spectrum potential? Epilepsia 2019;60 Suppl 1:22–36.
      1. Segal E, Wheless J, Moretz K, Penovich P, Patten A, Malhotra M. Perampanel in real-world clinical care of adolescent and adult patients with epilepsy: results from the retrospective phase IV PROVE study. Seizure 2022;98:87–94.
    MeSH Terms
    Acids
    Age of Onset
    Cohort Studies
    Diagnosis
    Epilepsy
    Epilepsy, Generalized
    Female
    Follow-Up Studies
    Humans
    Korea*
    Levetiracetam
    Multivariate Analysis
    Prescriptions
    Records
    Respect
    Seizures
    Metrics
    Share
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