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Without prompt treatment, the seizures can become resistant to benzodiazepines, leading to the progressive evolution of established, refractory, and super\u2010refractory SE. Studies in experimental animals have found impaired GABAergic inhibition and potentiated glutamatergic neurotransmission in SE animals. These alterations increase the number of active neurons and expand the seizure network. Here, we first discuss the changes in GABA\u2010A, NMDA, and AMPA receptor\u2010mediated synaptic transmission during SE and elaborate on emerging studies showing the neuronal consumption of alternate energy sources to cope with increased energy demand. Then, we discuss the clinical studies that have tested the efficacy of various benzodiazepines and other anticonvulsant agents in treating SE in prehospital and in\u2010hospital settings. Finally, we briefly summarize the ongoing clinical studies and the potential for other anticonvulsant agents to be tested for treating SE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Most seizures are self\u2010limiting, but some seizures change the brain such that a constant state of seizures, SE, is generated. These prolonged seizures can cause neuronal injury and increase the risk of death. We discuss the molecular mechanisms that sustain these seizures and the accompanying neuronal and network plasticity. We also review the current SE treatment and future directions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.70146","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T12:53:33Z","timestamp":1758027213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Status epilepticus: Updates on mechanisms and treatments"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-2061","authenticated-orcid":false,"given":"Suchitra","family":"Joshi","sequence":"first","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-1352","authenticated-orcid":false,"given":"Jaideep","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Neuroscience University of Virginia  Charlottesville Virginia USA"},{"name":"UVA Brain Institute University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1111\/epi.13121","article-title":"A definition and classification of status epilepticus \u2013 report of the ILAE task force on classification of status epilepticus","volume":"56","author":"Trinka E","year":"2015","journal-title":"Epilepsia"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1212\/WNL.46.4.1029","article-title":"A prospective, population\u2010based epidemiologic study of status epilepticus in Richmond, Virginia","volume":"46","author":"DeLorenzo 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