{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:57:15Z","timestamp":1785855435529,"version":"3.56.0"},"reference-count":82,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute symptomatic neonatal seizures are one of the most common neurological disorders in newborns admitted to neonatal intensive care units and require prompt treatment. Up to 50% of neonatal seizures are refractory to first\u2010line medications such as phenobarbital (PB), and another 30% fail second\u2010line therapy. Furthermore, antiseizure medications (ASMs) such as PB have short\u2010term adverse effects and may exert long\u2010term detrimental effects on neurodevelopment. Thus, the development of more effective and safer ASMs is an urgent medical need. Because of its multimodal mechanisms of action and neuroprotective activity as well as promising preclinical and clinical findings, topiramate (TPM) is currently among the most attractive ASMs for the treatment of PB\u2010refractory neonatal seizures. However, parenteral TPM is not clinically available, which restricts its use in most newborns with acute seizures. In this review, we critically discuss the current knowledge about TPM as a treatment for neonatal seizures and associated conditions. We describe both preclinical and clinical data and highlight that the neuroprotective activity of this drug, not shared by most other ASMs, may enhance the efficacy of therapeutic hypothermia to decrease adverse neurodevelopment after neonatal brain injury. In addition, we describe two novel intravenous formulations of TPM currently being developed for clinical use. One formulation uses the highly tolerable U.S. Food and Drug Administration (FDA)\u2013approved excipient meglumine for the preparation of an aqueous TPM solution, so is particularly suitable for neonates. We recommend prospective randomized controlled clinical trials designed to test the safety and efficacy of intravenous TPM for neonatal seizures. TPM doses in such trials should be based on the maintenance of effective plasma levels not achieved in most previous clinical studies with enteral administration of TPM suspensions. Furthermore, the potentially beneficial neuroprotective effects of TPM on adverse outcomes associated with neonatal seizures and their etiologies should be examined in such trials.<\/jats:p>","DOI":"10.1111\/epi.18563","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T14:59:19Z","timestamp":1753973959000},"page":"4091-4106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topiramate for the treatment of neonatal seizures and beyond"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-8973","authenticated-orcid":false,"given":"Wolfgang","family":"L\u00f6scher","sequence":"first","affiliation":[{"name":"Translational Neuropharmacology Lab, NIFE, Department of Experimental Otology of the ENT Clinics Hannover Medical School  Hannover Germany"},{"name":"PrevEp, Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6998-7753","authenticated-orcid":false,"given":"Janet S.","family":"Soul","sequence":"additional","affiliation":[{"name":"Fetal\u2010Neonatal Neurology Program, Department of Neurology Boston Children's Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"e_1_2_13_2_1","first-page":"381","volume-title":"Volpe's neurology of the newborn","author":"Abend 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