Volume 30, Issue 3 (September 2026)                   Physiol Pharmacol 2026, 30(3): 273-282 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Arvan H, Mehramiri A, Ansari Dezfouli M. Topiramate in refractory status epilepticus: a systematic review. Physiol Pharmacol 2026; 30 (3) :273-282
URL: http://ppj.phypha.ir/article-1-2580-en.html
Abstract:   (774 Views)

Epilepsy is a chronic neurological disease characterized by recurrent seizures and is caused by abnormal electrical activity in neuronal circuits. Refractory status epilepticus is a life-threatening condition that does not respond to first- and second-line anticonvulsant medications. Topiramate is a powerful antiseizure medication that is used in various types of epilepsy. This study aimed to investigate the effect of topiramate in treatment of refractory status epilepticus.
We have developed search strategies to identify articles related to the effect of topiramate on refractory status epilepticus. Our searches encompassed validated databases, including PubMed / MEDLINE, Scopus, Google Scholar, and Cochrane Library, from 2012 to May 2026. 
Of the 896 articles found in the preliminary search, 10 clinical studies were selected for structured review. The results of this study indicated that refractory status epilepticus occurs in about 38% of patients with status epilepticus and causes more mortality and disability. Acute symptomatic seizures tend to be resistant to treatment. Topiramate treatment ameliorated epileptic seizures in 194 cases out of 317 patients. Adverse effects, including pancreatitis and metabolic acidosis, and allergic reactions have been reported in rare cases. In conclusion, the available evidence suggests that topiramate may be a potentially useful adjunctive therapy for refractory status epilepticus, especially when administered early. However, reported studies are limited and most of them are based on observational data. Further well-designed prospective studies are required to evaluate its efficacy and safety.

 

Full-Text [PDF 401 kb]   (64 Downloads)    
Type of Manuscript: Review | Subject: Neurophysiology/Pharmacology

References
1. Akyıldız B N, Kumandaş S. Treatment of pediatric refractory status epilepticus with topiramate. Child’s Nervous System 2011; 27: 1425-1430. [DOI:10.1007/s00381-011-1432-y]
2. Asadi-Pooya A A, Jahromi M J, Izadi S, Emami Y. Treatment of refractory generalized convulsive status epilepticus with enteral topiramate in resource limited settings. Seizure 2015; 24: 114-117. [DOI:10.1016/j.seizure.2014.09.009]
3. Au Y K, Kananeh M F, Rahangdale R, Moore T E, Panza G A, Gaspard N, et al. Treatment of refractory status epilepticus with continuous intravenous anesthetic drugs: a systematic review. JAMA Neurology 2024; 81: 534-548. [DOI:10.1001/jamaneurol.2024.0108]
4. Bai Y-F, Zeng C, Jia M, Xiao B. Molecular mechanisms of topiramate and its clinical value in epilepsy. Seizure 2022; 98: 51-56. [DOI:10.1016/j.seizure.2022.03.024]
5. Besli G E, Karatoprak E Y, Yilmaz S. Efficacy and safety profile of intravenous levetiracetam versus phenytoin in convulsive status epilepticus and acute repetitive seizures in children. Epilepsy & Behavior 2020; 111: 107289. [DOI:10.1016/j.yebeh.2020.107289]
6. Brigo F, Bragazzi N L, Igwe S C, Nardone R, Trinka E. Topiramate in the treatment of generalized convulsive status epilepticus in adults: a systematic review with individual patient data analysis. Drugs 2017; 77: 67-74. [DOI:10.1007/s40265-016-0672-2]
7. Brigo F, Del Giovane C, Nardone R, Trinka E, Lattanzi S. Intravenous antiepileptic drugs in adults with benzodiazepine-resistant convulsive status epilepticus: a systematic review and network meta-analysis. Epilepsy & Behavior 2019; 101: 106466. [DOI:10.1016/j.yebeh.2019.106466]
8. Chimakurthy A K, Ramsay R E, Sabharwal V, Menon U. Safety, tolerability, and pharmacokinetics of weight-based IV loading dose of lacosamide in the ICU. Epilepsy & Behavior 2021; 114: 107449. [DOI:10.1016/j.yebeh.2020.107449]
9. Cock H R, Group E. Established status epilepticus treatment trial (ESETT). Epilepsia 2011; 52: 50-52. [DOI:10.1111/j.1528-1167.2011.03237.x]
10. Fariba K A, Saadabadi A. Topiramate. StatPearls [Internet]: StatPearls Publishing, 2024.
11. Fechner A, Hubert K, Jahnke K, Knake S, Konczalla J, Menzler K, et al. Treatment of refractory and superrefractory status epilepticus with topiramate: a cohort study of 106 patients and a review of the literature. Epilepsia 2019; 60: 2448-2458. [DOI:10.1111/epi.16382]
12. Fisher R S, Cross J H, French J A, Higurashi N, Hirsch E, Jansen F E, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58: 522-530. [DOI:10.1111/epi.13670]
13. Hakami T. Efficacy and tolerability of antiseizure drugs. Therapeutic Advances in Neurological Disorders 2021; 14: 17562864211037430. [DOI:10.1177/17562864211037430]
14. Hottinger A, Sutter R, Marsch S, Rüegg S. Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study. CNS Drugs 2012; 26: 761-772. [DOI:10.2165/11633090-000000000-00000]
15. Jehi L. Advances in therapy for refractory epilepsy. Annual Review of Medicine 2025; 76. [DOI:10.1146/annurev-med-050522-034458]
16. Kanner A M, Bicchi M M. Antiseizure medications for adults with epilepsy: a review. Journal of the American Medical Association 2022; 327: 1269-1281. [DOI:10.1001/jama.2022.3880]
17. Kapur J, Elm J, Chamberlain J M, Barsan W, Cloyd J, Lowenstein D, et al. Randomized trial of three anticonvulsant medications for status epilepticus. New England Journal of Medicine 2019; 381: 2103-2113. [DOI:10.1056/NEJMoa1905795]
18. Kellinghaus C, Rossetti A O, Trinka E, Lang N, May T W, Unterberger I, et al. Factors predicting cessation of status epilepticus in clinical practice: data from a prospective observational registry (SENSE). Annals of Neurology 2019; 85: 421-432. [DOI:10.1002/ana.25416]
19. Keskin-Güler S, Karadaş Ö, Atmaca M M, Özek S Ü, Yunisova G, Buluş E, et al. Enteral topiramate treatment in refractory status epilepticus. Epilepsy Research 2025; 213: 107551. [DOI:10.1016/j.eplepsyres.2025.107551]
20. Klowak J A, Hewitt M, Catenacci V, Duffett M, Rochwerg B, Jones K, Choong K. Levetiracetam versus phenytoin or fosphenytoin for second-line treatment of pediatric status epilepticus: a meta-analysis. Pediatric Critical Care Medicine 2021; 22: 480-491. [DOI:10.1097/PCC.0000000000002703]
21. Kortland L M, Alfter A, Bähr O, Carl B, Dodel R, Freiman T M, et al. Costs and cost-driving factors for acute treatment of adults with status epilepticus: a multicenter cohort study from Germany. Epilepsia 2016; 57: 2056-2066. [DOI:10.1111/epi.13584]
22. Lim S-N, Wu T, Tseng W-E J, Chiang H-I, Cheng M-Y, Lin W-R, Lin C-N. Efficacy and safety of perampanel in refractory and super-refractory status epilepticus: cohort study of 81 patients and literature review. Journal of Neurology 2021: 1-14. [DOI:10.1007/s00415-021-10506-9]
23. Löscher W, Soul J S. Topiramate for the treatment of neonatal seizures and beyond. Epilepsia 2025. [DOI:10.1111/epi.18563]
24. Madžar D, Kuramatsu J B, Gerner S T, Huttner H B. Assessing the value of topiramate in refractory status epilepticus. Seizure 2016; 38: 7-10. [DOI:10.1016/j.seizure.2016.03.003]
25. Niquet J, Lumley L, Baldwin R, Rossetti F, Schultz M, de Araujo Furtado M, et al. Early polytherapy for benzodiazepine-refractory status epilepticus. Epilepsy & Behavior 2019; 101: 106367. [DOI:10.1016/j.yebeh.2019.06.011]
26. Orlandi N, Bartolini E, Audenino D, Moja M C, Urso L, d’Orsi G, et al. Intravenous brivaracetam in status epilepticus: a multicentric retrospective study in Italy. Seizure 2021; 86: 70-76. [DOI:10.1016/j.seizure.2021.01.014]
27. Orlandi N, Gozzi A, Giovannini G, Turchi G, Cioclu M C, Vaudano A E, Meletti S. Recurrent status epilepticus: Clinical features and recurrence risk in an adult population. Seizure 2022; 97: 1-7. [DOI:10.1016/j.seizure.2022.02.012]
28. Panda P K, Panda P, Dawman L, Sharawat I K. Efficacy of lacosamide and phenytoin in status epilepticus: A systematic review. Acta Neurologica Scandinavica 2021; 144: 366-374. [DOI:10.1111/ane.13469]
29. Rohracher A, Kellinghaus C, Strzelczyk A. Topiramate, perampanel and brivaracetam in status epilepticus: How should they be used and what effect can be expected? Zeitschrift für Epileptologie 2018; 31: 256-261. [DOI:10.1007/s10309-018-0206-x]
30. Rosenthal E S, Claassen J, Wainwright M S, Husain A M, Vaitkevicius H, Raines S, et al. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Annals of Neurology 2017; 82: 342-352. [DOI:10.1002/ana.25008]
31. Santamarina E, Parejo Carbonell B, Sala J, Gutiérrez-Viedma Á, Miró J, Asensio M, et al. Use of intravenous brivaracetam in status epilepticus: a multicenter registry. Epilepsia 2019; 60: 1593-1601. [DOI:10.1111/epi.16094]
32. Sarangi S C, Kakkar A K, Kumar R, Gupta Y K. Effect of lamotrigine, levetiracetam & topiramate on neurobehavioural parameters & oxidative stress in comparison with valproate in rats. Indian Journal of Medical Research 2016; 144: 104-111. [DOI:10.4103/0971-5916.193296]
33. Scheffer I E, Berkovic S, Capovilla G, Connolly M B, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Zeitschrift für Epileptologie 2018; 31: 296-306. [DOI:10.1007/s10309-018-0218-6]
34. Schubert-Bast S, Zöllner J P, Ansorge S, Hapfelmeier J, Bonthapally V, Eldar-Lissai A, 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: 911-920. [DOI:10.1111/epi.14729]
35. Shishmanova-Doseva M, Peychev L, Yoanidu L, Uzunova Y, Atanasova M, Georgieva K, Tchekalarova J. Anticonvulsant effects of topiramate and lacosamide on pilocarpine-induced status epilepticus in rats: a role of reactive oxygen species and inflammation. International Journal of Molecular Sciences 2021; 22: 2264. [DOI:10.3390/ijms22052264]
36. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain 2011; 134: 2802-2818. [DOI:10.1093/brain/awr215]
37. Stojanova V, Rossetti A. Oral topiramate as an add-on treatment for refractory status epilepticus. Acta Neurologica Scandinavica 2012; 125: 7-11. [DOI:10.1111/j.1600-0404.2011.01562.x]
38. Suttichaimongkol T, Tiamkao S, Sawanyawisuth K. The efficacy of topiramate in status epilepticus, experience from Thailand. Neurology Asia 2012; 17.
39. Synowiec A S, Yandora K A, Yenugadhati V, Valeriano J P, Schramke C J, Kelly K M. The efficacy of topiramate in adult refractory status epilepticus: experience of a tertiary care center. Epilepsy research 2012; 98: 232-237. [DOI:10.1016/j.eplepsyres.2011.09.017]
40. Tanaka T, Ihara M, Fukuma K, Mishra N K, Koepp M J, Guekht A, Ikeda A. Pathophysiology, diagnosis, prognosis, and prevention of poststroke epilepsy: clinical and research implications. Neurology 2024; 102: e209450. [DOI:10.1212/WNL.0000000000209450]
41. Tantikittichaikul S, Johnson J, Laengvejkal P, DeToledo J. Topiramate-induced hyperammonemic encephalopathy in a patient with mental retardation: a case report and review of the literature. Epilepsy & Behavior Case Reports 2015; 4: 84-85. [DOI:10.1016/j.ebcr.2014.09.001]
42. Tarulli A, Drislane F W. The use of topiramate in refractory status epilepticus. Neurology 2004; 62: 837-837. [DOI:10.1212/WNL.62.5.837]
43. Welling L C, Rabelo N N, Yoshikawa M H, Telles J P M, Teixeira M J, Figueiredo E G. Efficacy of topiramate as an add-on therapy in patients with refractory status epilepticus: a short systematic review. Revista Brasileira de Terapia Intensiva 2021; 33: 440-444. [DOI:10.5935/0103-507X.20210054]
44. Zhang Y, Liu Y, Liao Q, Liu Z. Preferential antiseizure medications in pediatric patients with convulsive status epilepticus: a systematic review and network meta-analysis. Clinical Drug Investigation 2021; 41: 1-17. [DOI:10.1007/s40261-020-00975-7]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.