Midazolam as a rescue medication for epileptic seizures at home and in the hospital ward Review article
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Published:
Mar 1, 2026
Keywords:
buccal midazolam, benzodiazepines, seizures
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Abstract
Buccal midazolam is an effective and safe rescue medication used to terminate epileptic seizures at home and in the prehospital setting. Prompt intervention is crucial to preventing the development of status epilepticus. Midazolam’s efficacy is comparable to other benzodiazepines, and its easy route of administration and good bioavailability make it a first-line treatment.
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Kurkowska-Jastrzębska, I. (2026). Midazolam as a rescue medication for epileptic seizures at home and in the hospital ward. Medycyna Faktow (J EBM), 19(4(69), 506-512. https://doi.org/10.24292/01.MF.0425.04
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References
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7. Carreño M, Kim-Wisskirchen IH, Forcadell Ferré M et al. Midazolam Oromucosal Solution for the Management of Prolonged Convulsive Seizures in Adult Outpatients: Addressing Unmet Needs in Europe. Clin Drug Investig. 2025; 45(12): 923-33. http://doi.org/10.1007/s40261-025-01493-0.
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10. Osborne A, Taylor L, Reuber M et al. Pre-hospital care after a seizure: evidence base and United Kingdom management guidelines. Seizure. 2015; 24: 82-7.
11. Pina-Garza JE, Chez M, Cloyd J et al. Outpatient management of prolonged seizures and seizure clusters to prevent progression to a higher-level emergency: Consensus recommendations of an expert working group. Epileptic Disord. 2024; 26(4): 484-97.
12. Jafarpour S, Pisani F, Neshagh H et al. Seizure clusters: definition, prevalence, consequences and acute management. Seizure. 2018; 68: 9-15.
13. Asadi-Pooya AA, Nei M, Sharan A et al. Seizure clusters in drug-resistant focal epilepsy. Epilepsia. 2016; 57(9): e187-90. http://doi.org/10.1111/epi.13465.
14. Detyniecki K, O’Bryan J, Choezom T et al. Prevalence and predictors of seizure clusters: A prospective observational study of adult patients with epilepsy. Epilepsy Behav. 2018; 88: 349-56. http://doi.org/10.1016/j.yebeh.2018.09.035.
15. Jafarpour S, Fong MWK, Detyniecki K et al. Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study. Pediatr Neurol. 2022; 137: 22-9. http://doi.org/10.1016/j.pediatrneurol.2022.08.014.
16. Bauman K, Kao A, Penovich P et al. Rescue therapies for seizure clusters: a review of intranasal benzodiazepines and other options. Front Neurol. 2021; 12: 636045.
17. Sillanpää M, Schmidt D. Long-term outcome of childhood-onset epilepsy: a prospective population-based study. Brain. 2008; 131(Pt 4): 938-94.
18. Trinka E, Cock H, Hesdorffer D et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015; 56(10): 1515-23.
19. Pallin DJ, Goldstein JN, Moussally JS et al. Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med. 2008; 1: 97-105. https://doi.org/10.1007/s12245-008-0024-4.
20. Dobesberger J, Ristić AJ, Walser G et al. Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures – A video-EEG analysis. Epilepsy Behav. 2015; 49: 111-7. https://doi.org/10.1016/j.yebeh.2015.03.023.
21. Beljemann JP. Status epilepticus in adults. Lancet Neurol. 2015; 14: 615-24.
22. Knake S, Hamer HM, Rosenow F. Status epilepticus: a critical review. Epilepsy Behav. 2009; 15(1): 10-4. https://doi.org/10.1016/j.yebeh.2009.02.027.
23. Naylor DE. Mechanisms of seizure termination and implications for treatment of status epilepticus. Epileptic Disord. 2014; 16(Suppl 2): S69-S83.
24. Becker DA, Sarma D, Gidal BE et al. Rescue medication strategies for seizure clusters: a review and clinical perspective. Neurol Ther. 2023; 12: 1439-55.
25. Gainza-Lein M, Hameed B, Saxena S et al. Efficacy of early treatment in status epilepticus and seizure clusters. JAMA Neurol. 2018; 75: 410-8.
26. Heuser K, Olsen KB, Ulvin LB et al. Chapter 5.Modern Treatment of Status Epilepticus in Adults. In: Epilepsy. Czuczwar SJ (ed.). Exon Publications, Brisbane (AU) 2022.
27. Cruickshank M, Imamura M, Counsell C et al. Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence. J Neurol. 2022; 269(7): 3420-9. http://doi.org/10.1007/s00415-022-10979-2.
28. McIntyre J, Robertson S, Norris E et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005; 366(9481): 205-10. http://doi.org/10.1016/S0140-6736(05)66909-7.
29. McMullan J, Sasson C, Pancioli A et al. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis. Acad Emerg Med. 2010; 17(6): 575-82. http://doi.org/10.1111/j.1553-2712.2010.00751.x.
30. Brigo F, Nardone R, Tezzon F et al. Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: A systematic review with meta-analysis. Epilepsy Behav. 2015; 49: 325-36. http://doi.org/10.1016/j.yebeh.2015.02.030.
31. Möller L, Fisch U, Habermehl L et al. Treating status epilepticus in clinical practice-a multi-national survey in Germany, Austria, and Switzerland. Front Neurol. 2025; 16: 1685993. http://doi.org/10.3389/fneur.2025.1685993.
32. Alldredge BK, Gelb AM, Isaacs SM et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001; 345(9): 631-7.
2. Peter JU, Dieudonné P, Zolk O. Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example. Pharmaceuticals (Basel). 2024; 17(4): 473. http://doi.org/10.3390/ph17040473.
3. Silbergleit R, Durkalski V, Lowenstein D et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012; 366(7): 591-600. http://doi.org/10.1056/NEJMoa1107494.
4. Mazurkiewicz-Bełdzińska M, Szmuda M, Zawadzka M et al. Current treatment of convulsive status epilepticus – a therapeutic protocol and review. Anaesthesiol Intensive Ther. 2014; 46: 293-300.
5. Public Assessment Report. Scientific discussion Nasolam 2.5 mg, 3.75 mg and 5 mg nasal spray, solution in single-dose container (midazolam hydrochloride).
6. bbMullhi R, Hayton T, Midgley-Hunt A et al. Guidance for: The acute management of status epilepticus in adult patients. J Intensive Care Soc. 2025; 26(2): 249-62. http://doi.org/10.1177/17511437251321338.
7. Carreño M, Kim-Wisskirchen IH, Forcadell Ferré M et al. Midazolam Oromucosal Solution for the Management of Prolonged Convulsive Seizures in Adult Outpatients: Addressing Unmet Needs in Europe. Clin Drug Investig. 2025; 45(12): 923-33. http://doi.org/10.1007/s40261-025-01493-0.
8. Ma Y, Lu C, Hastie P et al. Medications used for seizure-emergency management in the UK community: A clinical practice research datalink retrospective database study. Epilepsia Open. 2025; 10(4): 1023-33. http://doi.org/10.1002/epi4.70035.
9. Chin RF, Neville BG, Peckham C et al.; NLSTEPSS Collaborative Group. Incidence, cause, and short-term outcome of convulsive status epilepticus in childhood: prospective population-based study. Lancet. 2006; 368(9531): 222-29.
10. Osborne A, Taylor L, Reuber M et al. Pre-hospital care after a seizure: evidence base and United Kingdom management guidelines. Seizure. 2015; 24: 82-7.
11. Pina-Garza JE, Chez M, Cloyd J et al. Outpatient management of prolonged seizures and seizure clusters to prevent progression to a higher-level emergency: Consensus recommendations of an expert working group. Epileptic Disord. 2024; 26(4): 484-97.
12. Jafarpour S, Pisani F, Neshagh H et al. Seizure clusters: definition, prevalence, consequences and acute management. Seizure. 2018; 68: 9-15.
13. Asadi-Pooya AA, Nei M, Sharan A et al. Seizure clusters in drug-resistant focal epilepsy. Epilepsia. 2016; 57(9): e187-90. http://doi.org/10.1111/epi.13465.
14. Detyniecki K, O’Bryan J, Choezom T et al. Prevalence and predictors of seizure clusters: A prospective observational study of adult patients with epilepsy. Epilepsy Behav. 2018; 88: 349-56. http://doi.org/10.1016/j.yebeh.2018.09.035.
15. Jafarpour S, Fong MWK, Detyniecki K et al. Prevalence and Predictors of Seizure Clusters in Pediatric Patients With Epilepsy: The Harvard-Yale Pediatric Seizure Cluster Study. Pediatr Neurol. 2022; 137: 22-9. http://doi.org/10.1016/j.pediatrneurol.2022.08.014.
16. Bauman K, Kao A, Penovich P et al. Rescue therapies for seizure clusters: a review of intranasal benzodiazepines and other options. Front Neurol. 2021; 12: 636045.
17. Sillanpää M, Schmidt D. Long-term outcome of childhood-onset epilepsy: a prospective population-based study. Brain. 2008; 131(Pt 4): 938-94.
18. Trinka E, Cock H, Hesdorffer D et al. A definition and classification of status epilepticus – Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015; 56(10): 1515-23.
19. Pallin DJ, Goldstein JN, Moussally JS et al. Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med. 2008; 1: 97-105. https://doi.org/10.1007/s12245-008-0024-4.
20. Dobesberger J, Ristić AJ, Walser G et al. Duration of focal complex, secondarily generalized tonic-clonic, and primarily generalized tonic-clonic seizures – A video-EEG analysis. Epilepsy Behav. 2015; 49: 111-7. https://doi.org/10.1016/j.yebeh.2015.03.023.
21. Beljemann JP. Status epilepticus in adults. Lancet Neurol. 2015; 14: 615-24.
22. Knake S, Hamer HM, Rosenow F. Status epilepticus: a critical review. Epilepsy Behav. 2009; 15(1): 10-4. https://doi.org/10.1016/j.yebeh.2009.02.027.
23. Naylor DE. Mechanisms of seizure termination and implications for treatment of status epilepticus. Epileptic Disord. 2014; 16(Suppl 2): S69-S83.
24. Becker DA, Sarma D, Gidal BE et al. Rescue medication strategies for seizure clusters: a review and clinical perspective. Neurol Ther. 2023; 12: 1439-55.
25. Gainza-Lein M, Hameed B, Saxena S et al. Efficacy of early treatment in status epilepticus and seizure clusters. JAMA Neurol. 2018; 75: 410-8.
26. Heuser K, Olsen KB, Ulvin LB et al. Chapter 5.Modern Treatment of Status Epilepticus in Adults. In: Epilepsy. Czuczwar SJ (ed.). Exon Publications, Brisbane (AU) 2022.
27. Cruickshank M, Imamura M, Counsell C et al. Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence. J Neurol. 2022; 269(7): 3420-9. http://doi.org/10.1007/s00415-022-10979-2.
28. McIntyre J, Robertson S, Norris E et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005; 366(9481): 205-10. http://doi.org/10.1016/S0140-6736(05)66909-7.
29. McMullan J, Sasson C, Pancioli A et al. Midazolam versus diazepam for the treatment of status epilepticus in children and young adults: a meta-analysis. Acad Emerg Med. 2010; 17(6): 575-82. http://doi.org/10.1111/j.1553-2712.2010.00751.x.
30. Brigo F, Nardone R, Tezzon F et al. Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: A systematic review with meta-analysis. Epilepsy Behav. 2015; 49: 325-36. http://doi.org/10.1016/j.yebeh.2015.02.030.
31. Möller L, Fisch U, Habermehl L et al. Treating status epilepticus in clinical practice-a multi-national survey in Germany, Austria, and Switzerland. Front Neurol. 2025; 16: 1685993. http://doi.org/10.3389/fneur.2025.1685993.
32. Alldredge BK, Gelb AM, Isaacs SM et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001; 345(9): 631-7.