Seizure management and prescription patterns of anticonvulsants in Dravet syndrome: A multicenter cohort study from Germany and review of literature.

Susanne Schubert-Bast, Markus Wolff, Adelheid Wiemer-Kruel, Sarah von Spiczak, Regina Trollmann, Philipp S Reif, Clive Pritchard, Tilman Polster, Bernd A Neubauer, Thomas Mayer, Daniel Macdonald, Gerhard Kurlemann, Gerhard Kluger, Karl Martin Klein, Matthias Kieslich, Lara Kay, Malin Kalski, John Irwin, Arne Herting, Joe Carroll, Ulrich Bettendorf, Thomas Bast, Felix Rosenow, Adam Strzelczyk

Journal: Epilepsy & behavior : E&B 2020;98(Pt A):88-95

PMID: 31301455

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Abstract

OBJECTIVE

The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of real-world evidence on medicine utilization of patients with DS in Europe.

METHODS

Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe.

RESULTS

The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed.

SIGNIFICANCE

This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common AED combinations being in line with clinical guidelines/best practice, there is no discernable impact of best treatment on seizure frequency. We find a higher use of bromide in Germany compared with other real-world evidence in Europe.

Address: Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.; Department of Neuropediatrics, University of Tübingen, Tübingen, Germany; Zentrum für Sozialpädiatrie & Neuropädiatrie (DBZ), Vivantes Klinikum Neukölln, Berlin, Germany.; Epilepsy Center Kork, Kehl-Kork, Germany.; Northern German Epilepsy Centre for Children and Adolescents, Kiel-Raisdorf, Germany.; Department of Neuropediatrics, Friedrich-Alexander University, Erlangen, Germany.; Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.; Wickenstones Ltd., Goring Heath, United Kingdom.; Epilepsy Center Bethel, Bielefeld, Germany.; Department of Neuropediatrics, Justus-Liebig-University Giessen, Giessen, Germany.; Epilepsy Center Kleinwachau, Dresden-Radeberg, Germany.; Department of Neuropediatrics, University of Münster, Münster, Germany.; Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik Vogtareuth, Germany; Research Institute "Rehabilitation, Transition, and Palliation", PMU Salzburg, Salzburg, Austria.; Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.; Zogenix International Limited, Maidenhead, United Kingdom.; Neuropediatric Practice, Hirschaid, Germany.; Epilepsy Center Kork, Kehl-Kork, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany; Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany. Electronic address: [email protected].

DOI: 10.1016/j.yebeh.2019.06.021

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MeSH Terms: Anticonvulsants, Clobazam, Cohort Studies, Drug Prescriptions, Drug Therapy, Combination, Epilepsies, Myoclonic, Female, Germany, Humans, Male, Seizures, Topiramate, Valproic Acid