{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:04:17Z","timestamp":1782255857355,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021729","name":"Medizinische Fakult\u00e4t der Albert-Ludwigs-Universit\u00e4t Freiburg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess the efficacy and tolerability of fenfluramine (FFA) with concomitant potassium bromide (BR) in patients with Dravet syndrome (DS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study, conducted within the German compassionate use program, analyzed BR doses and serum levels before and after FFA initiation, adverse events (AEs), seizure reduction, and symptoms changes using the Clinical Global Impression of Change (CGIC) scale. Timepoints were defined as T0 (baseline), T1 (FFA initiation), T2 and T3 (first and second BR level measurement after FFA initiation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010two patients (median age 8.9\u2009years, range 2.2\u201326.7) treated with BR were included. Median duration of BR\u2013FFA combination therapy was 7\u2009months (range 0\u201328). BR doses were reduced at least once in 11 patients (50%) as a precaution or because of increased serum levels. At T3, mean BR dose was significantly lower compared to T0 (1217\u2009mg\/day, SD\u2009=\u2009699 vs. 1755\u2009mg\/day, SD\u2009=\u2009752.2;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04), but BR levels showed no significant difference between T2 or T3 and baseline. In contrast, for patients with stable BR doses (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200914), mean BR level significantly increased from baseline (1376\u2009mg\/L, SD\u2009=\u2009345.7) to T2 (1762\u2009mg\/L, SD\u2009=\u2009553.3;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). AEs were reported in 15 patients (68.2%) during the combination therapy, with the most common being somnolence (59.1%) and loss of appetite (22.7%). In 40.9% either FFA or BR were discontinued due to sedation. The responder rate for seizure reduction was 68.4% at 3\u2009months and 76.9% at 6\u2009months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>BR levels increased significantly after FFA initiation when BR doses were not reduced, contributing to adverse events\u2014primarily somnolence\u2014and resulting in the discontinuation of BR or FFA in some patients. Close monitoring of BR levels is crucial to minimize the risk of adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>This study investigated the combination of fenfluramine (FFA) and potassium BR in treating Dravet syndrome. It was found that it is effective in reducing seizures, but BR levels often went up after starting FFA, which caused side effects like drowsiness in many patients. In some cases, these side effects were serious enough that physicians had to stop either BR or FFA. The study highlights the need for careful monitoring of BR levels when using this combination to avoid potential side effects by reducing the BR dose early if needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70079","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T12:29:17Z","timestamp":1752755357000},"page":"1323-1333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and tolerability of fenfluramine with concomitant potassium bromide in patients with Dravet syndrome"],"prefix":"10.1002","volume":"10","author":[{"given":"Milka","family":"Pringsheim","sequence":"first","affiliation":[{"name":"Clinic for Neuropediatrics and Neurorehabilitation Epilepsy Center for Children and Adolescents, Sch\u00f6n Klinik Vogtareuth  Vogtareuth Germany"},{"name":"Congenital Heart Disease and Pediatric Cardiology, German Heart Centre Munich TUM Universit\u00e4tsklinikum  Munich Germany"},{"name":"Department of Pediatrics, Institute of Rehabilitation, Institute of Rehabilitation, Transition and Palliation of Neurologically Ill Children Paracelsus Medical University Salzburg  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kluger","sequence":"additional","affiliation":[{"name":"Clinic for Neuropediatrics and Neurorehabilitation Epilepsy Center for Children and Adolescents, Sch\u00f6n Klinik Vogtareuth  Vogtareuth Germany"},{"name":"Department of Pediatrics, Institute of Rehabilitation, Institute of Rehabilitation, Transition and Palliation of Neurologically Ill Children Paracelsus Medical University Salzburg  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-9915","authenticated-orcid":false,"given":"Adam","family":"Strzelczyk","sequence":"additional","affiliation":[{"name":"Department of Neurology Goethe\u2010University Frankfurt Epilepsy Center Frankfurt Rhine\u2010Main  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1545-7364","authenticated-orcid":false,"given":"Susanne","family":"Schubert\u2010Bast","sequence":"additional","affiliation":[{"name":"Department of Neurology Goethe\u2010University Frankfurt Epilepsy Center Frankfurt Rhine\u2010Main  Frankfurt am Main Germany"},{"name":"Department of Pediatric Epileptology Goethe\u2010University Frankfur  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mayer","sequence":"additional","affiliation":[{"name":"Epilepsy Center Kleinwachau  Radeberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Glauche","sequence":"additional","affiliation":[{"name":"Epilepsy Center Kleinwachau  Radeberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiltrud","family":"Muhle","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics Christian\u2010Albrechts\u2010University Kiel &amp; 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