Penovich PE, Buelow J, Steinberg K, Sirven J, Wheless J. Burden of seizure clusters on patients with epilepsy and caregivers: survey of patient, caregiver, and clinician perspectives. Neurologist. 2017;22(6):207–14. https://doi.org/10.1097/NRL.0000000000000140.

Article  PubMed  Google Scholar 

Cloyd J, Haut S, Carrazana E, Rabinowicz AL. Overcoming the challenges of developing an intranasal diazepam rescue therapy for the treatment of seizure clusters. Epilepsia. 2021;62(4):846–56. https://doi.org/10.1111/epi.16847.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jafarpour S, Hirsch LJ, Gainza-Lein M, Kellinghaus C, Detyniecki K. Seizure cluster: definition, prevalence, consequences, and management. Seizure. 2019;68:9–15. https://doi.org/10.1016/j.seizure.2018.05.013.

Article  PubMed  Google Scholar 

Wirrell EC, Nabbout R, Scheffer IE, Alsaadi T, Bogacz A, French JA, et al. Methodology for classification and definition of epilepsy syndromes with list of syndromes: report of the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63(6):1333–48. https://doi.org/10.1111/epi.17237.

Article  PubMed  Google Scholar 

Bausch Health US, LLC. Diastat® C-IV (diazepam rectal gel). Full prescribing information. Bridgewater (NJ): Bausch Health US, LLC; 2023.

Neurelis, Inc. Valtoco® (diazepam nasal spray). Full prescribing information. San Diego (CA): Neurelis, Inc.; 2023.

UCB, Inc. Nayzilam® (midazolam nasal spray). Full prescribing information. Smyrna (GA): UCB, Inc.; 2023.

Fisher RS, Bartfeld E, Cramer JA. Use of an online epilepsy diary to characterize repetitive seizures. Epilepsy Behav. 2015;47:66–71. https://doi.org/10.1016/j.yebeh.2015.04.022.

Article  PubMed  Google Scholar 

European Medicines Agency. Buccolam. 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/buccolam. Accessed 11 May 2023.

Neuraxpharm. Important information about Buccolam (midazolam) oromucosal solution. 2022. https://static.neuraxpharm.com/wp-content/uploads/sites/19/2022/09/01110313/nxuk062207-buccolam-seal-elimination-hcp-digi.pdf. Accessed 15 May 2023.

Electronic Medicines Compendium. Diazepam Desitin 5 mg rectal solution. 2019. https://www.medicines.org.uk/emc/product/2997/smpc. Accessed 8 Sep 2021.

Stillhart C, Vucicevic K, Augustijns P, Basit AW, Batchelor H, Flanagan TR, et al. Impact of gastrointestinal physiology on drug absorption in special populations: an UNGAP review. Eur J Pharm Sci. 2020;147:105280. https://doi.org/10.1016/j.ejps.2020.105280.

Article  CAS  PubMed  Google Scholar 

Detyniecki K, O’Bryan J, Choezom T, Rak G, Ma C, Zhang S, et al. Prevalence and predictors of seizure clusters: a prospective observational study of adult patients with epilepsy. Epilepsy Behav. 2018;88:349–56. https://doi.org/10.1016/j.yebeh.2018.09.035.

Article  PubMed  Google Scholar 

Cramer JA, Faught E, Davis C, Misra SN, Carrazana E, Rabinowicz AL. Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. Epilepsy Behav. 2022;134:108811. https://doi.org/10.1016/j.yebeh.2022.108811.

Article  PubMed  Google Scholar 

Carter B, Cook G, Bray L, Collingwood A, Saron H, Rouncefield-Swales A. Parents’/caregivers’ fears and concerns about their child’s epilepsy: a scoping review. PLoS ONE. 2022;17(9):e0274001. https://doi.org/10.1371/journal.pone.0274001.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ertan D, Hubert-Jacquot C, Maillard L, Sanchez S, Jansen C, Fracomme L, et al. Anticipatory anxiety of epileptic seizures: an overlooked dimension linked to trauma history. Seizure. 2021;85:64–9. https://doi.org/10.1016/j.seizure.2020.12.006.

Article  PubMed  Google Scholar 

Weiss A, Canetti L, David SB, Reuveni I, Ekstein D. Seizure phobia: a distinct psychiatric disorder among people with epilepsy. Seizure. 2022;95:26–32. https://doi.org/10.1016/j.seizure.2021.12.009.

Article  PubMed  Google Scholar 

Hingray C, McGonigal A, Kotwas I, Micoulaud-Franchi JA. The relationship between epilepsy and anxiety disorders. Curr Psychiatry Rep. 2019;21(6):40. https://doi.org/10.1007/s11920-019-1029-9.

Article  PubMed  Google Scholar 

Kanner AM. Management of psychiatric and neurological comorbidities in epilepsy. Nat Rev Neurol. 2016;12(2):106–16. https://doi.org/10.1038/nrneurol.2015.243.

Article  CAS  PubMed  Google Scholar 

Munger Clary HM, Salpekar JA. Should adult neurologists play a role in the management of the most common psychiatric comorbidities? Practical considerations. Epilepsy Behav. 2019;98(Pt B):309–13. https://doi.org/10.1016/j.yebeh.2018.10.020.

Article  PubMed  Google Scholar 

Gaitatzis A, Carroll K, Majeed A, Jain WS. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia. 2004;45(12):1613–22. https://doi.org/10.1111/j.0013-9580.2004.17504.x.

Article  PubMed  Google Scholar 

Cereghino JJ. Identification and treatment of acute repetitive seizures in children and adults. Curr Treat Opt Neurol. 2007;9(4):249–55. https://doi.org/10.1007/s11940-007-0011-8.

Article  Google Scholar 

Kapur J, Long L, Dixon-Salazar T. Consequences: bench to home. Epilepsia. 2022;63(Suppl. 1):S14–24. https://doi.org/10.1111/epi.17342.

Article  PubMed  Google Scholar 

Patel AD, Becker DA. Introduction to use of an acute seizure action plan for seizure clusters and guidance for implementation. Epilepsia. 2022;63(Suppl. 1):S25-33. https://doi.org/10.1111/epi.17344.

Article  PubMed  Google Scholar 

Kumar G. Evaluation and management of drug resistant epilepsy in children. Curr Probl Pediatr Adolesc Health Care. 2021;51(7): 101035. https://doi.org/10.1016/j.cppeds.2021.101035.

Article  PubMed  Google Scholar 

Fine A, Wirrell EC. Seizures in children. Pediatr Rev. 2020;41(7):321–47. https://doi.org/10.1542/pir.2019-0134.

Article  PubMed  Google Scholar 

Higdon LM, Sperling MR. A review of a diazepam nasal spray for the treatment of acute seizure clusters and prolonged seizures. Expert Rev Neurother. 2021;21(11):1207–12. https://doi.org/10.1080/14737175.2021.1965880.

Article  CAS  PubMed  Google Scholar 

Gidal B, Detyniecki K. Rescue therapies for seizure clusters: pharmacology and target of treatments. Epilepsia. 2022;63(Suppl. 1):S34-44. https://doi.org/10.1111/epi.17341.

Article  PubMed  PubMed Central  Google Scholar 

Gidal B, Welty T, Cokley J, Farrell M, Shafer P, Rabinowicz AL, et al. Opportunities for community pharmacists to counsel patients with epilepsy and seizure clusters to overcome barriers and foster appropriate treatment. J Pharm Pract. 2022;2022:6570. https://doi.org/10.1177/08971900221126570.

Article  Google Scholar 

Holsti M, Dudley N, Schunk J, Adelgais K, Greenberg R, Olsen C, et al. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med. 2010;164(8):747–53. https://doi.org/10.1001/archpediatrics.2010.130.

Article  PubMed  Google Scholar 

Hospira, Inc. Midazolam injection (midazolam injection). Full prescribing information. Lake Forest: Hospira Inc.; 2023.

Google Scholar 

Kriel RL, Cloyd JC, Pellock JM, Mitchell WG, Cereghino JJ, Rosman NP. Rectal diazepam gel for treatment of acute repetitive seizures. The North American Diastat Study Group. Pediatr Neurol. 1999;20(4):282–8. https://doi.org/10.1016/s0887-8994(98)00156-8.

Article  CAS  PubMed  Google Scholar 

Dreifuss FE, Rosman NP, Cloyd JC, Pellock JM, Kuzniecky RI, Lo WD, et al. A comparison of rectal diazepam gel and placebo for acute repetitive seizures. N Engl J Med. 1998;338(26):1869–75. https://doi.org/10.1056/NEJM199806253382602.

Article  CAS  PubMed  Google Scholar 

Detyniecki K, Van Ess PJ, Sequeira DJ, Wheless JW, Meng TC, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: a randomized, double-blind, placebo-controlled trial. Epilepsia. 2019;60(9):1797–808. https://doi.org/10.1111/epi.15159.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wheless JW, Meng TC, Van Ess PJ, Detyniecki K, Sequeira DJ, Pullman WE. Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: an open-label extension trial. Epilepsia. 2019;60(9):1809–19. https://doi.org/10.1111/epi.16300.

Article  CAS  PubMed  Google Scholar 

Neurelis, Inc. Valtoco instructions for use. San Diego: Neurelis Inc; 2022.

Google Scholar 

Tarquinio D, Dlugos D, Wheless JW, Desai J, Carrazana E, Rabinowicz AL. Safety of diazepam nasal spray in children and adolescents with epilepsy: results from a long-term phase 3 safety study. Pediatr Neurol. 2022;132:50–5. https://doi.org/10.1016/j.pediatrneurol.2022.04.011.

Article  PubMed  Google Scholar 

Wheless JW, Miller I, Hogan RE, Dlugos D, Biton V, Cascino GD, et al. Final results from a phase 3, long-term, open-label, repeat-dose safety study of diazepam nasal spray for seizure clusters in patients with epilepsy. Epilepsia. 2021;62(10):2485–95. https://doi.org/10.1111/epi.17041.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neurelis, Inc. Neurelis signs exclusive licensing agreement with Aculys Pharma for the development and commercialization of Valtoco® (diazepam nasal spray) in Japan and the Asia-Pacific Region. 2022. https://neurelis.com/neurelis-signs-exclusive-licensing-agreement-aculys-pharma-development-and-commercialization. Accessed 15 May 2023.

Lopez-Toledano MA, Guerra C, Misra SN, Carrazana E, Rabinowicz AL. Study design of an open-label pharmacokinetic and safety trial of diazepam nasal spray (Valtoco) in children 2-5 years old with seizure clusters. In: Presented at: American Epilepsy Society Annual Meeting; December 3–7, 2021; Chicago (IL); 2021.

Dean P, O’Hara K, Brooks L, Shinnar R, Bougher G, Santilli N. Managing acute seizures: new rescue delivery option and resources to assist school nurses. NASN Sch Nurse. 2021;36(6):346–54. https://doi.org/10.1177/1942602X211026333.

Article  PubMed  PubMed Central  Google Scholar 

Almohaish S, Sandler M, Brophy GM. Time is brain: acute control of repetitive seizures and status epilepticus using alternative routes of administration of benzodiazepines. J Clin Med. 2021;10(8):1754. https://doi.org/10.3390/jcm10081754.