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Nervenheilkunde 2019; 38(12): 887-901
DOI: 10.1055/a-0987-8517
Schwerpunkt
© Georg Thieme Verlag KG Stuttgart · New York

Medikamentöse Therapie von epileptischen Anfällen und Epilepsien

Medical treatment of acute seizures and epilepsy
Lara Kay
1   Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Goethe-Universität Frankfurt, Frankfurt am Main
2   LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-Universität Frankfurt, Frankfurt am Main
,
Sebastian Bauer∗
1   Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Goethe-Universität Frankfurt, Frankfurt am Main
2   LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-Universität Frankfurt, Frankfurt am Main
,
Felix Rosenow∗
1   Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Goethe-Universität Frankfurt, Frankfurt am Main
2   LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-Universität Frankfurt, Frankfurt am Main
,
Adam Strzelczyk∗
1   Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Goethe-Universität Frankfurt, Frankfurt am Main
2   LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-Universität Frankfurt, Frankfurt am Main
,
Johann Philipp Zöllner∗
1   Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Goethe-Universität Frankfurt, Frankfurt am Main
2   LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-Universität Frankfurt, Frankfurt am Main
› Author Affiliations
Further Information

Publication History

Publication Date:
17 December 2019 (online)

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ZUSAMMENFASSUNG

Fast jede aktive Epilepsie bedarf einer medikamentösen Therapie durch Antianfallsmedikamente (Antiiktalia). Ziel ist die Anfallsfreiheit des Patienten bei gleichzeitig guter Tolerabilität. Zur Dauertherapie fokaler Epilepsien steht eine Reihe von Antianfallsmedikamenten zur Verfügung, bei generalisierten Epilepsien ist die Auswahl kleiner. Die Wahl des Antianfallsmedikamentes sollte neben dem Epilepsiesyndrom an den individuellen Wünschen und der Lebenssituation des Patienten, seinen Komorbiditäten und dem Nebenwirkungsprofil ausgerichtet werden. Meist wird man deshalb neuere Antianfallsmedikamente bevorzugen. Durch die Entwicklung neuer Medikamente erhöht sich die Chance einer individuell gut verträglichen und erfolgreichen Therapie. Dem gegenüber stehen höhere Therapiekosten der meisten neueren Antianfallsmedikamente. Die meisten epileptischen Anfälle sind selbstlimitierend. Ein prolongierter epileptischer Anfall muss jedoch schnell und ausreichend hoch dosiert mit Benzodiazepinen behandelt werden, um so einen therapierefraktären Verlauf abwenden zu können und das Outcome des Patienten zu verbessern.

ABSTRACT

Almost every active epilepsy requires medical treatment. The aim is to keep the patient free of seizures while at the same time ensuring good tolerability. A number of drugs are available for the long-term treatment of focal epilepsies, whereas the choice is more limited for generalized epilepsies. The choice of an anti-seizure drug should be based on the patient’s expectations and life situation, his co-morbidities and the side effect profile of the anti-seizure drug, in addition to the epilepsy syndrome. Newer anti-seizure drugs will therefore usually be preferred. The development of newer drugs increases the chance of an individually well-tolerated and successful therapy. On the other hand, the therapy costs of most of the newer anti-seizure drugs are higher. Most epileptic seizures are self-limiting. However, a prolonged epileptic seizure must be treated with benzodiazepines quickly and in sufficiently high doses to avert a refractory course of status epilepticus and to improve the outcome of the patient.

Key words

Epilepsy - antiepileptic drugs - status epilepticus - benzodiazepines
 

  • Literatur

  • 1 Forsgren L, Beghi E, Oun A. et al The epidemiology of epilepsy in Europe – a systematic review. Eur J Neurol 2005; 12 (04) 245-53
    CrossrefPubMedGoogle Scholar
  • 2 Ertl J, Hapfelmeier J, Peckmann T. et al Guideline conform initial monotherapy increases in patients with focal epilepsy: A population-based study on German health insurance data. Seizure 2016; 41: 9-15
    CrossrefPubMedGoogle Scholar
  • 3 Hamer HM, Dodel R, Strzelczyk A. et al Prevalence, utilization, and costs of antiepileptic drugs for epilepsy in Germany – a nationwide population-based study in children and adults. Journal of neurology 2012; 259 (11) 2376-84
    CrossrefPubMedGoogle Scholar
  • 4 Fisher RS, Acevedo C, Arzimanoglou A. et al ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 2014; 55 (04) 475-82
    CrossrefPubMedGoogle Scholar
  • 5 Strzelczyk A, Griebel C, Lux W. et al The Burden of Severely Drug-Refractory Epilepsy: A Comparative Longitudinal Evaluation of Mortality, Morbidity, Resource Use, and Cost Using German Health Insurance Data. Frontiers in neurology 2017; 8: 712
    CrossrefPubMedGoogle Scholar
  • 6 Willems LM, Richter S, Watermann N. et al Trends in resource utilization and prescription of anticonvulsants for patients with active epilepsy in Germany from 2003 to 2013 – A ten-year overview. Epilepsy Behav 2018; 83: 28-35
    CrossrefPubMedGoogle Scholar
  • 7 Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. The New England journal of medicine 2011; 365 (10) 919-26
    CrossrefPubMedGoogle Scholar
  • 8 Kwan P, Arzimanoglou A, Berg AT. et al Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51 (06) 1069-77
    PubMedGoogle Scholar
  • 9 Rosenow F, Bast T, Czech T. et al Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian, German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment. Epilepsia 2016; 57 (08) 1215-20
    CrossrefPubMedGoogle Scholar
  • 10 Li-Na Z, Deng C. et al Indirect comparison of third-generation antiepileptic drugs as adjunctive treatment for uncontrolled focal epilepsy. Epilepsy Res 2018; 139: 60-72
    CrossrefPubMedGoogle Scholar
  • 11 Bodalia PN, Grosso AM, Sofat R. et al Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials. Br J Clin Pharmacol 2013; 76 (05) 649-67
    CrossrefPubMedGoogle Scholar
  • 12 Zhuo C, Jiang R, Li G. et al Efficacy and Tolerability of Second and Third Generation Anti-epileptic Drugs in Refractory Epilepsy: A Network Meta-Analysis. Sci Rep 2017; 7 (01) 2535
    CrossrefPubMedGoogle Scholar
  • 13 Otoul C, Arrigo C. et al Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy. Clin Neuropharmacol 2005; 28 (02) 72-8
    CrossrefPubMedGoogle Scholar
  • 14 Brodie MJ, Sills GJ. Combining antiepileptic drugs--rational polytherapy?. Seizure 2011; 20 (05) 369-75
    CrossrefPubMedGoogle Scholar
  • 15 Marson AG, Al-Kharusi AM, Alwaidh M. et al The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369 9566 1000-15
    CrossrefPubMedGoogle Scholar
  • 16 Brodie MJ, Perucca E, Ryvlin P. et al Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68 (06) 402-8
    CrossrefPubMedGoogle Scholar
  • 17 Baulac M, Brodie MJ, Patten A. et al Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol 2012; 11 (07) 579-88
    CrossrefPubMedGoogle Scholar
  • 18 Marson AG, Al-Kharusi AM, Alwaidh M. et al The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007; 369 9566 1016-26
    CrossrefPubMedGoogle Scholar
  • 19 Glauser T, Ben-Menachem E. et al Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013; 54 (03) 551-63
    CrossrefPubMedGoogle Scholar
  • 20 Kwan P, Brodie MJ. Clinical trials of antiepileptic medications in newly diagnosed patients with epilepsy. Neurology 2003; 60 11 (Suppl. 04) S2-12
    PubMedGoogle Scholar
  • 21 Christe W, Kramer G, Vigonius U. et al A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy. Epilepsy Res 1997; 26 (03) 451-60
    CrossrefPubMedGoogle Scholar
  • 22 Tomson T, Battino D. et al Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol 2018; 17 (06) 530-8
    CrossrefPubMedGoogle Scholar
  • 23 Intravooth T, Staack AM, Juerges K. et al Antiepileptic drugs-induced hyponatremia: Review and analysis of 560 hospitalized patients. Epilepsy research 2018; 143: 7-10
    CrossrefPubMedGoogle Scholar
  • 24 Doeser A, Dickhof G, Reitze M. et al Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug. Brain 2015; 138 Pt 2 371-87
    CrossrefPubMedGoogle Scholar
  • 25 Willems LM, Zöllner JP, Paule E. et al Eslicarbazepine acetate in epilepsies with focal and secondary generalised seizures: systematic review of current evidence. Expert review of clinical pharmacology 2018; 11 (03) 309-24
    CrossrefPubMedGoogle Scholar
  • 26 Zadeh WW, Escartin A. et al Efficacy and safety of lacosamide as first add-on or later adjunctive treatment for uncontrolled partial-onset seizures: A multicentre open-label trial. Seizure 2015; 31: 72-9
    CrossrefPubMedGoogle Scholar
  • 27 Giraldez BG, Toledano R, Garcia-Morales I. et al Long-term efficacy and safety of lacosamide monotherapy in the treatment of partial-onset seizures: A multicenter evaluation. Seizure 2015; 29: 119-22
    CrossrefPubMedGoogle Scholar
  • 28 Bauer S, Willems LM, Paule E. et al The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience. Ther Adv Neurol Disord 2017; 10 (02) 103-26
    CrossrefPubMedGoogle Scholar
  • 29 Brodie MJ, Richens A, Yuen AW. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group. Lancet 1995; 345 8948 476-9
    CrossrefPubMedGoogle Scholar
  • 30 Guerrini R, Dravet C, Genton P. et al Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia 1998; 39 (05) 508-12
    CrossrefPubMedGoogle Scholar
  • 31 Glauser TA, Cnaan A. et al Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 2010; 362 (09) 790-9
    CrossrefPubMedGoogle Scholar
  • 32 Löscher W, Gillard M, Sands ZA. et al Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond. CNS Drugs 2016; 30 (11) 1055-77
    CrossrefPubMedGoogle Scholar
  • 33 Lambrechts DA, Sadzot B, van Paesschen W. et al Efficacy and safety of levetiracetam in clinical practice: results of the SKATE trial from Belgium and The Netherlands. Seizure 2006; 15 (06) 434-42
    CrossrefPubMedGoogle Scholar
  • 34 Meencke HJ, Buyle S. Assessment of a dose-response relationship of levetiracetam. Eur J Neurol 2006; 13 (09) 942-6
    CrossrefPubMedGoogle Scholar
  • 35 Werhahn KJ, Trinka E, Dobesberger J. et al A randomized, double-blind comparison of antiepileptic drug treatment in the elderly with new-onset focal epilepsy. Epilepsia 2015; 56 (03) 450-9
    CrossrefPubMedGoogle Scholar
  • 36 Willems LM, Hamer HM, Knake S. et al General Trends in Prices and Prescription Patterns of Anticonvulsants in Germany between 2000 and 2017: Analysis of National and Cohort-Based Data. Appl Health Econ Health Policy 2019 doi:10.1007/s40258-019-00487-2
    PubMedGoogle Scholar
  • 37 Strzelczyk A, Klein KM, Willems LM. et al Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. Expert review of clinical pharmacology 2016; 9 (05) 637-45
    CrossrefPubMedGoogle Scholar
  • 38 Steinig I, von Podewils F, Möddel G. et al Postmarketing experience with brivaracetam in the treatment of epilepsies: A multicenter cohort study from Germany. Epilepsia 2017; 58 (07) 1208-16
    CrossrefPubMedGoogle Scholar
  • 39 Strzelczyk A, Kay L, Bauer S. et al Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia 2018; 59 (08) 1549-56
    CrossrefPubMedGoogle Scholar
  • 40 Löscher W. Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy. CNS Drugs 2002; 16 (10) 669-94
    CrossrefPubMedGoogle Scholar
  • 41 McLean MJ, Macdonald RL. Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture. J Pharmacol Exp Ther 1986; 237 (03) 1001-11
    PubMedGoogle Scholar
  • 42 Schmidt D, Jacob R, Loiseau P. et al Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial. Epilepsy Res 1993; 15 (01) 67-77
    CrossrefPubMedGoogle Scholar
  • 43 Marinas A, Villanueva V, Giraldez BG. et al Efficacy and tolerability of zonisamide in idiopathic generalized epilepsy. Epileptic Disord 2009; 11 (01) 61-6
    PubMedGoogle Scholar
  • 44 Vajda FJ. New antiepileptic drugs. J Clin Neurosci 2000; 7 (02) 88-101
    CrossrefPubMedGoogle Scholar
  • 45 Arroyo S, Dodson WE, Privitera MD. et al Randomized dose-controlled study of topiramate as first-line therapy in epilepsy. Acta Neurol Scand 2005; 112 (04) 214-22
    CrossrefPubMedGoogle Scholar
  • 46 Panebianco M, Al-Bachari S, Weston J. et al Gabapentin add-on treatment for drug-resistant focal epilepsy. Cochrane Database Syst Rev 2018; 10: CD001415
    PubMedGoogle Scholar
  • 47 Beydoun A, Uthman BM, Kugler AR. et al Safety and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology 2005; 64 (03) 475-80
    CrossrefPubMedGoogle Scholar
  • 48 Kwan P, Brodie MJ, Kalviainen R. et al Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial. Lancet Neurol 2011; 10 (10) 881-90
    CrossrefPubMedGoogle Scholar
  • 49 Strzelczyk A, Willems LM, Willig S. et al Perampanel in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. Expert review of clinical pharmacology 2015; 8 (06) 733-40
    CrossrefPubMedGoogle Scholar
  • 50 Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist. Epilepsia 2015; 56 (01) 12-27
    CrossrefPubMedGoogle Scholar
  • 51 Tsai JJ, Wu T, Leung H. et al Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings. Acta Neurol Scand 2018; 137 (04) 378-91
    CrossrefPubMedGoogle Scholar
  • 52 Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. The Dianalund experience. Acta Neurol Scand 2016; 134 (05) 374-7
    PubMedGoogle Scholar
  • 53 Chiron C, Dulac O. Epilepsy: Vigabatrin treatment and visual field loss. Nat Rev Neurol 2011; 7 (04) 189-90
    CrossrefPubMedGoogle Scholar
  • 54 Coppola G, Besag F. et al Current role of rufinamide in the treatment of childhood epilepsy: literature review and treatment guidelines. Eur J Paediatr Neurol 2014; 18 (06) 685-90
    CrossrefPubMedGoogle Scholar
  • 55 Pellock JM, Faught E. et al Felbamate: consensus of current clinical experience. Epilepsy Res 2006; 71 2–3 89-101
    CrossrefPubMedGoogle Scholar
  • 56 Chiron C. Stiripentol for the treatment of seizures associated with Dravet syndrome. Expert Rev Neurother 2019; 19 (04) 301-10
    CrossrefPubMedGoogle Scholar
  • 57 Strzelczyk A, Kortland LM, Knake S. et al Stiripentol for the treatment of super-refractory status epilepticus. Acta Neurol Scand 2015; 132 (06) 435-9
    CrossrefPubMedGoogle Scholar
  • 58 Devinsky O, Patel AD, Cross JH. et al Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome. The New England journal of medicine 2018; 378 (20) 1888-97
    CrossrefPubMedGoogle Scholar
  • 59 Devinsky O, Cross JH. et al Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med 2017; 376 (21) 2011-20
    CrossrefPubMedGoogle Scholar
  • 60 O’Connell BK, Gloss D, Devinsky O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav 2017; 70 Pt B 341-8
    CrossrefPubMedGoogle Scholar
  • 61 Jenssen S, Gracely EJ, Sperling MR. How long do most seizures last? A systematic comparison of seizures recorded in the epilepsy monitoring unit. Epilepsia 2006; 47 (09) 1499-503
    CrossrefPubMedGoogle Scholar
  • 62 Trinka E, Cock H. et al A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015; 56 (10) 1515-23
    CrossrefPubMedGoogle Scholar
  • 63 Strzelczyk A, Ansorge S. et al Costs, length of stay, and mortality of super-refractory status epilepticus: A population-based study from Germany. Epilepsia 2017; 58 (09) 1533-41
    CrossrefPubMedGoogle Scholar
  • 64 Schubert-Bast S, Zöllner JP, Ansorge S. et al Burden and epidemiology of status epilepticus in infants, children, and adolescents: A population-based study on German health insurance data. Epilepsia 2019; 60 (05) 911-20
    CrossrefPubMedGoogle Scholar
  • 65 Diener HC. Leitlinien für Diagnostik und Therapie in der Neurologie: Herausgegeben von der Kommission „Leitlinien“ der DGN. Berlin: 2012
    Google Scholar
  • 66 Prasad M, Krishnan PR, Sequeira R. et al Anticonvulsant therapy for status epilepticus. The Cochrane database of systematic reviews 2014 9 CD003723
    PubMedGoogle Scholar
  • 67 Alldredge BK, Gelb AM, Isaacs SM. et al A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. The New England journal of medicine 2001; 345 (09) 631-7
    CrossrefPubMedGoogle Scholar
  • 68 Kellinghaus C, Rossetti AO, Trinka E. et al SENSE registry for status epilepticus. Epilepsia 2018; 59 (Suppl. 02) 150-4
    CrossrefPubMedGoogle Scholar
  • 69 Kellinghaus C, Rossetti AO, Trinka E. et al Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE). Annals of neurology 2019; 85 (03) 421-32
    PubMedGoogle Scholar
  • 70 Strzelczyk A, Kay L, Kellinghaus C. et al Concepts for Prehospital and Initial In-hospital Therapy of Status Epilepticus. Neurology International Open 2017; 01 (03) E217-E23
    Article in Thieme ConnectGoogle Scholar
  • 71 Schubert-Bast S, Strzelczyk A. Therapie des akuten konvulsiven Anfalls und Status epilepticus im Kindesalter. Zeitschrift für Epileptologie 2019; 32 (02) 116-25
    CrossrefGoogle Scholar
  • 72 Silbergleit R, Durkalski V, Lowenstein D. et al Intramuscular versus intravenous therapy for prehospital status epilepticus. The New England journal of medicine 2012; 366 (07) 591-600
    CrossrefPubMedGoogle Scholar
  • 73 Dreifuss FE, Rosman NP, Cloyd JC. et al A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med 1998; 338 (26) 1869-75
    CrossrefPubMedGoogle Scholar
  • 74 McIntyre J, Robertson S, Norris E. et al Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 2005; 366 9481 205-10
    CrossrefPubMedGoogle Scholar
  • 75 Lahat E, Goldman M, Barr J. et al Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. Bmj 2000; 321 7253 83-6
    CrossrefPubMedGoogle Scholar
  • 76 de Haan GJ, van der Geest P, Doelman G. et al A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia 2010; 51 (03) 478-82
    CrossrefPubMedGoogle Scholar
  • 77 Kay L, Reif PS, Belke M. et al Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures. Epilepsia 2015; 56 (09) 1408-14
    CrossrefPubMedGoogle Scholar
  • 78 Kadel J, Bauer S, Hermsen AM. et al Use of Emergency Medication in Adult Patients with Epilepsy: A Multicentre Cohort Study from Germany. CNS Drugs 2018; 32 (08) 771-81
    CrossrefPubMedGoogle Scholar
  • 79 Strzelczyk A, Reese JP, Dodel R. et al Cost of epilepsy: a systematic review. PharmacoEconomics 2008; 26 (06) 463-76
    CrossrefPubMedGoogle Scholar
  • 80 Lagae L, Schoonjans AS, Gammaitoni AR. et al A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox-Gastaut syndrome. Epilepsia 2018; 59 (10) 1881-8
    CrossrefPubMedGoogle Scholar