Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
CNS Drugs
Published in: CNS Drugs 9/2022

Open Access 01-09-2022 | Pharmacokinetics | Review Article

Benzodiazepines in the Management of Seizures and Status Epilepticus: A Review of Routes of Delivery, Pharmacokinetics, Efficacy, and Tolerability

Authors: Ricardo Kienitz, Lara Kay, Isabelle Beuchat, Sarah Gelhard, Sophie von Brauchitsch, Catrin Mann, Alexandra Lucaciu, Jan-Hendrik Schäfer, Kai Siebenbrodt, Johann-Philipp Zöllner, Susanne Schubert-Bast, Felix Rosenow, Adam Strzelczyk, Laurent M. Willems

Published in: CNS Drugs | Issue 9/2022

Login to get access

Abstract

Status epilepticus (SE) is an acute, life-threatening medical condition that requires immediate, effective therapy. Therefore, the acute care of prolonged seizures and SE is a constant challenge for healthcare professionals, in both the pre-hospital and the in-hospital settings. Benzodiazepines (BZDs) are the first-line treatment for SE worldwide due to their efficacy, tolerability, and rapid onset of action. Although all BZDs act as allosteric modulators at the inhibitory gamma-aminobutyric acid (GABA)A receptor, the individual agents have different efficacy profiles and pharmacokinetic and pharmacodynamic properties, some of which differ significantly. The conventional BZDs clonazepam, diazepam, lorazepam and midazolam differ mainly in their durations of action and available routes of administration. In addition to the common intravenous, intramuscular and rectal administrations that have long been established in the acute treatment of SE, other administration routes for BZDs—such as intranasal administration—have been developed in recent years, with some preparations already commercially available. Most recently, the intrapulmonary administration of BZDs via an inhaler has been investigated. This narrative review provides an overview of the current knowledge on the efficacy and tolerability of different BZDs, with a focus on different routes of administration and therapeutic specificities for different patient groups, and offers an outlook on potential future drug developments for the treatment of prolonged seizures and SE.

Graphical Abstract

Literature
1.
2.
Roberg LE, Monsson O, Kristensen SB, Dahl SM, Ulvin LB, Heuser K, et al. Prediction of long-term survival after status epilepticus using the ACD score. JAMA Neurol. 2022;79(6):604–13.PubMedCrossRef
3.
Schubert-Bast S, Zollner JP, 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(5):911–20.PubMedCrossRef
4.
Poukas VS, Pollard JR, Anderson CT. Rescue therapies for seizures. Curr Neurol Neurosci Rep. 2011;11(4):418–22.PubMedCrossRef
5.
Humphries LK, Eiland LS. Treatment of acute seizures: is intranasal midazolam a viable option? J Pediatr Pharmacol Ther. 2013;18(2):79–87.PubMedPubMedCentral
6.
Rey E, Treluyer JM, Pons G. Pharmacokinetic optimization of benzodiazepine therapy for acute seizures Focus on delivery routes. Clin Pharmacokinet. 1999;36(6):409–24.PubMedCrossRef
7.
Anderson GD, Saneto RP. Current oral and non-oral routes of antiepileptic drug delivery. Adv Drug Deliv Rev. 2012;64(10):911–8.PubMedCrossRef
8.
Kadel J, Bauer S, Hermsen AM, Immisch I, Kay L, Klein KM, et al. Use of emergency medication in adult patients with epilepsy: a multicentre cohort study from Germany. CNS Drugs. 2018;32(8):771–81.PubMedCrossRef
9.
Mula M. New non-intravenous routes for benzodiazepines in epilepsy: a clinician perspective. CNS Drugs. 2017;31(1):11–7.PubMedCrossRef
10.
Lathers CM, Jim KF, Spivey WH. A comparison of intraosseous and intravenous routes of administration for antiseizure agents. Epilepsia. 1989;30(4):472–9.PubMedCrossRef
11.
Kapur J, Macdonald RL. Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. J Neurosci. 1997;17(19):7532–40.PubMedPubMedCentralCrossRef
12.
McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, 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.PubMedCrossRef
13.
Scott RC, Besag FM, Boyd SG, Berry D, Neville BG. Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics. Epilepsia. 1998;39(3):290–4.PubMedCrossRef
14.
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 paediatric patients with epilepsy. Arch Pediatr Adolesc Med. 2010;164(8):747–53.PubMedCrossRef
15.
Thakker A, Shanbag P. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures. J Neurol. 2013;260(2):470–4.PubMedCrossRef
16.
Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, 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.PubMedCrossRef
17.
Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2.PubMedCrossRef
18.
Rosenow F. Status epilepticus im Erwachsenenalter. In: Diener HC, Weimar C, editors. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag; 2012.
19.
Strzelczyk A, Ansorge S, Hapfelmeier J, Bonthapally V, Erder MH, Rosenow F. Costs, length of stay, and mortality of super-refractory status epilepticus: a population-based study from Germany. Epilepsia. 2017;58(9):1533–41.PubMedCrossRef
20.
Neligan A, Noyce AJ, Gosavi TD, Shorvon SD, Kohler S, Walker MC. Change in mortality of generalized convulsive status epilepticus in high-income countries over time: a systematic review and meta-analysis. JAMA Neurol. 2019;76(8):897–905.PubMedPubMedCentralCrossRef
21.
Lowenstein DH, Alldredge BK. Status epilepticus at an urban public hospital in the 1980s. Neurology. 1993;43(3 Pt 1):483–8.PubMedCrossRef
22.
Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, 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.PubMedCrossRef
23.
Sathe AG, Underwood E, Coles LD, Elm JJ, Silbergleit R, Chamberlain JM, et al. Patterns of benzodiazepine underdosing in the established status epilepticus treatment trial. Epilepsia. 2021;62(3):795–806.PubMedPubMedCentralCrossRef
24.
Kellinghaus C, Rossetti AO, Trinka T, Lang N, May TW, Unterberger I, et al. Factors predicting cessation of status epilepticus in clinical practice: Data from a prospective observational registry (SENSE). Ann Neurol. 2019;85(3):421–32.
25.
Willems LM, Bauer S, Jahnke K, Voss M, Rosenow F, Strzelczyk A. Therapeutic options for patients with refractory status epilepticus in palliative settings or with a limitation of life-sustaining therapies: a systematic review. CNS Drugs. 2020;34(8):801–26.
26.
27.
Martinez C, Sullivan T, Hauser WA. Prevalence of acute repetitive seizures (ARS) in the United Kingdom. Epilepsy Res. 2009;87(2–3):137–43.PubMedCrossRef
28.
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.PubMedCrossRef
29.
Cereghino JJ, Mitchell WG, Murphy J, Kriel RL, Rosenfeld WE, Trevathan E. Treating repetitive seizures with a rectal diazepam formulation: a randomized study. The North American Diastat Study Group. Neurology. 1998;51(5):1274–82.PubMedCrossRef
30.
Rose AB, McCabe PH, Gilliam FG, Smith BJ, Boggs JG, Ficker DM, et al. Occurrence of seizure clusters and status epilepticus during inpatient video-EEG monitoring. Neurology. 2003;60(6):975–8.PubMedCrossRef
31.
Haut SR, Lipton RB, LeValley AJ, Hall CB, Shinnar S. Identifying seizure clusters in patients with epilepsy. Neurology. 2005;65(8):1313–5.PubMedCrossRef
32.
Di Gennaro G, Picardi A, Sparano A, Mascia A, Meldolesi GN, Grammaldo LG, et al. Seizure clusters and adverse events during pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper. Clin Neurophysiol. 2012;123(3):486–8.PubMedCrossRef
33.
Herzog AG, Frye CA. Progesterone Trial Study G. Allopregnanolone levels and seizure frequency in progesterone-treated women with epilepsy. Neurology. 2014;83(4):345–8.PubMedPubMedCentralCrossRef
34.
Maguire MJ, Nevitt SJ. Treatments for seizures in catamenial (menstrual-related) epilepsy. Cochrane Database Syst Rev. 2019;10:13225.
35.
Ferastraoaru V, Goldenholz DM, Chiang S, Moss R, Theodore WH, Haut SR. Characteristics of large patient-reported outcomes: where can one million seizures get us? Epilepsia Open. 2018;3(3):364–73.PubMedPubMedCentralCrossRef
36.
Goldenholz DM, Rakesh K, Kapur K, Gainza-Lein M, Hodgeman R, Moss R, et al. Different as night and day: patterns of isolated seizures, clusters, and status epilepticus. Epilepsia. 2018;59(5):e73–7.PubMedPubMedCentralCrossRef
37.
Möddel G, Kellinghaus C, Strzelczyk A. Initial treatment of status epilepticus. Z Epileptol. 2018;31:245–9.
38.
Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, et al. Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the guideline committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61.PubMedPubMedCentralCrossRef
39.
Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Pharmacokinetic comparison of sublingual lorazepam with intravenous, intramuscular, and oral lorazepam. J Pharm Sci. 1982;71(2):248–52.PubMedCrossRef
40.
Treiman DM. Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia. 1989;30(Suppl 2):S4-10.PubMedCrossRef
41.
Ameer B, Greenblatt DJ. Lorazepam: a review of its clinical pharmacological properties and therapeutic uses. Drugs. 1981;21(3):162–200.PubMedCrossRef
42.
Greenblatt DJ. Clinical pharmacokinetics of oxazepam and lorazepam. Clin Pharmacokinet. 1981;6(2):89–105.PubMedCrossRef
43.
Arya R, Gulati S, Kabra M, Sahu JK, Kalra V. Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study. Epilepsia. 2011;52(4):788–93.PubMedCrossRef
44.
Waltregny A, Dargent J. Preliminary study of parenteral lorazepam in status epilepticus. Acta Neurol Belg. 1975;75(5):219–29.PubMed
45.
Walker JE, Homan RW, Vasko MR, Crawford IL, Bell RD, Tasker WG. Lorazepam in status epilepticus. Ann Neurol. 1979;6(3):207–13.PubMedCrossRef
46.
Leppik IE, Derivan AT, Homan RW, Walker J, Ramsay RE, Patrick B. Double-blind study of lorazepam and diazepam in status epilepticus. JAMA. 1983;249(11):1452–4.PubMedCrossRef
47.
Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339(12):792–8.PubMedCrossRef
48.
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591–600.PubMedPubMedCentralCrossRef
49.
Qureshi A, Wassmer E, Davies P, Berry K, Whitehouse WP. Comparative audit of intravenous lorazepam and diazepam in the emergency treatment of convulsive status epilepticus in children. Seizure. 2002;11(3):141–4.PubMedCrossRef
50.
Chamberlain JM, Okada P, Holsti M, Mahajan P, Brown KM, Vance C, et al. Lorazepam vs diazepam for paediatric status epilepticus: a randomized clinical trial. JAMA. 2014;311(16):1652–60.PubMedCrossRef
51.
Appleton R, Sweeney A, Choonara I, Robson J, Molyneux E. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol. 1995;37(8):682–8.PubMedCrossRef
52.
Welch RD, Nicholas K, Durkalski-Mauldin VL, Lowenstein DH, Conwit R, Mahajan PV, et al. Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the paediatric population. Epilepsia. 2015;56(2):254–62.PubMedPubMedCentralCrossRef
53.
Alvarez V, Lee JW, Drislane FW, Westover MB, Novy J, Dworetzky BA, et al. Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicentre comparison. Epilepsia. 2015;56(8):1275–85.PubMedPubMedCentralCrossRef
54.
Nordt SP, Clark RF. Midazolam: a review of therapeutic uses and toxicity. J Emerg Med. 1997;15(3):357–65.PubMedCrossRef
55.
Agency EM. Buccolam: EPAR - Product Information. European Medicines Agency.
56.
Drug Information. FDA Label & American Society of Health-System Pharmacists 2014. 2014.
57.
Haschke M, Suter K, Hofmann S, Witschi R, Frohlich J, Imanidis G, et al. Pharmacokinetics and pharmacodynamics of nasally delivered midazolam. Br J Clin Pharmacol. 2010;69(6):607–16.PubMedPubMedCentralCrossRef
58.
Knoester PD, Jonker DM, Van Der Hoeven RTM, Vermeij TAC, Edelbroek PM, Brekelmans GJ, et al. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers. Br J Clin Pharmacol. 2002;53(5):501–7.PubMedPubMedCentralCrossRef
59.
Wermeling DP, Record KA, Archer SM, Rudy AC. A pharmacokinetic and pharmacodynamic study, in healthy volunteers, of a rapidly absorbed intranasal midazolam formulation. Epilepsy Res. 2009;83(2–3):124–32.PubMedCrossRef
60.
Wermeling DP, Record KA, Kelly TH, Archer SM, Clinch T, Rudy AC. Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers. Anesth Analg. 2006;103(2):344–9.PubMedCrossRef
61.
FDA Label Midazolam Injection. US Food and Drug Administration.
62.
FDA Label NAYZILAM. US Food and Drug Administration.
63.
64.
65.
66.
Kay L, Merkel N, von Blomberg A, Willems LM, Bauer S, Reif PS, et al. Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study. Ann Clin Transl Neurol. 2019;6(12):2413–25.PubMedPubMedCentralCrossRef
67.
Kay L, Reif PS, Belke M, Bauer S, Frund D, Knake S, et al. Intranasal midazolam during presurgical epilepsy monitoring is well tolerated, delays seizure recurrence, and protects from generalized tonic-clonic seizures. Epilepsia. 2015;56(9):1408–14.PubMedCrossRef
68.
von Blomberg A, Kay L, Knake S, Fuest S, Zollner JP, Reif PS, et al. Efficacy, tolerability, and safety of concentrated intranasal midazolam spray as emergency medication in epilepsy patients during video-EEG monitoring. CNS Drugs. 2020;34(5):545–53.CrossRef
69.
Ulvi H, Yoldas T, Müngen B, Yigiter R. Continuous infusion of midazolam in the treatment of refractory geralized convulsive status epilepticus. Neurol Sci. 2002;23(4):177–82.PubMedCrossRef
70.
Prasad A, Worrall BB, Bertram EH, Bleck TP. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia. 2001;42(3):380–6.PubMedCrossRef
71.
Singhi S, Murthy A, Singhi P, Jayashree. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol. 2002;17(2):106–10.
72.
Chamberlain JM, Altieri MA, Futterman C, Young GM, Ochsenschlager DW, Waisman Y. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997;13(2):92–4.PubMedCrossRef
73.
Galdames-Contreras D, Carrasco-Poblete E, Aguilera-Olivares L, Fabres-Oyarzo L, Galdames-Poblete D. Intramuscular midazolam in the initial treatment of status epilepticus. Rev Neurologia. 2006;42(6):332–5.CrossRef
74.
Momen AA, Azizi Malamiri R, Nikkhah A, Jafari M, Fayezi A, Riahi K, et al. Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children. Eur J Paediatr Neurol. 2015;19(2):149–54.PubMedCrossRef
75.
Scott RC, Besag FMC, Neville BGR. Buccal midazolam and rectal diazepam for treatment of prolonged seizures in childhood and adolescence: a randomised trial. Lancet. 1999;353(9153):623–6.PubMedCrossRef
76.
Kutlu NO, Dogrul M, Yakinci C, Soylu H. Buccal midazolam for treatment of prolonged seizures in children. Brain Develop. 2003;25(4):275–8.CrossRef
77.
Nakken KO, Lossius MI. Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizures or status epilepticus. Acta Neurol Scand. 2011;124(2):99–103.PubMedCrossRef
78.
Hardmeier M, Zimmermann R, Rüegg S, Pflüger M, Deuster S, Suter K, et al. Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers. Clin Pharmacol Ther. 2012;91(5):856–62.PubMedCrossRef
79.
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.PubMedPubMedCentralCrossRef
80.
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.PubMedCrossRef
81.
Mahmoudian T, Mohammad MZ. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav. 2004;5(2):253–5.PubMedCrossRef
82.
Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: Prospective randomised study. Brit Med J. 2000;321(7253):83–6.PubMedPubMedCentralCrossRef
83.
De Haan GJ, Van Der Geest P, Doelman G, Bertram E, Edelbroek P. A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia. 2010;51(3):478–82.PubMedCrossRef
84.
Owusu KA, Dhakar MB, Bautista C, McKimmy D, Cotugno S, Sukumar N, et al. Comparison of intranasal midazolam versus intravenous lorazepam for seizure termination and prevention of seizure clusters in the adult epilepsy monitoring unit. Epilepsy Behav. 2019;98(Pt A):161–7.PubMedCrossRef
85.
Sutter R, Kaplan PW. Transnasal revolution? The promise of midazolam spray to prevent seizure clusters. CNS Drugs. 2020;34(5):555–7.PubMedCrossRef
86.
87.
Bojanic Z, Bojanic N, Bojanic V, Lazovic M. Drug interactions with diazepam. Acta Medica Medianae. 2011;Corpus ID: 51776045.
88.
Leppee M, Culig J, Eric M, Sijanovic S. The effects of benzodiazepines in pregnancy. Acta Neurol Belg. 2010;110(2):163–7.PubMed
89.
Full Prescribing Information VALTOCO (diazepam nasal spray): Food and Drug Agency (FDA); 2020.
90.
Mandelli M, Tognoni G, Garattini S. Clinical pharmacokinetics of diazepam. Clin Pharmacokinet. 1978;3(1):72–91.PubMedCrossRef
91.
Klotz U, Antonin KH, Bieck PR. Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat. J Pharmacol Exp Ther. 1976;199(1):67–73.PubMed
92.
Sperling MR, Haas KF, Krauss G, Seif Eddeine H, Henney HR 3rd, Rabinowicz AL, et al. Dosing feasibility and tolerability of intranasal diazepam in adults with epilepsy. Epilepsia. 2014;55(10):1544–50.PubMedCrossRef
93.
Thiessen JJ, Sellers EM, Denbeigh P, Dolman L. Plasma protein binding of diazepam and tolbutamide in chronic alcoholics. J Clin Pharmacol. 1976;16(7):345–51.PubMedCrossRef
94.
Vozeh S. Pharmacokinetic of benzodiazepines in old age. Schweiz Med Wochenschr. 1981;111(47):1789–93.PubMed
95.
Hooper WD, Dickinson RG, Dunstan PR, Pendlebury SC, Eadie MJ. Oxcarbazepine: preliminary clinical and pharmacokinetic studies on a new anticonvulsant. Clin Exp Neurol. 1987;24:105–12.PubMed
96.
Agarwal SK, Kriel RL, Brundage RC, Ivaturi VD, Cloyd JC. A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers. Epilepsy Res. 2013;105(3):362–7.PubMedCrossRef
97.
Gizurarson S, Gudbrandsson FK, Jonsson H, Bechgaard E. Intranasal administration of diazepam aiming at the treatment of acute seizures: clinical trials in healthy volunteers. Biol Pharm Bull. 1999;22(4):425–7.PubMedCrossRef
98.
Ivaturi VD, Riss JR, Kriel RL, Siegel RA, Cloyd JC. Bioavailability and tolerability of intranasal diazepam in healthy adult volunteers. Epilepsy Res. 2009;84(2–3):120–6.PubMedCrossRef
99.
Ivaturi VD, Riss JR, Kriel RL, Cloyd JC. Pharmacokinetics and tolerability of intranasal diazepam and midazolam in healthy adult volunteers. Acta Neurol Scand. 2009;120(5):353–7.PubMedCrossRef
100.
Garnett WR, Barr WH, Edinboro LE, Karnes HT, Mesa M, Wannarka GL. Diazepam autoinjector intramuscular delivery system versus diazepam rectal gel: a pharmacokinetic comparison. Epilepsy Res. 2011;93(1):11–6.PubMedCrossRef
101.
Lamson MJ, Sitki-Green D, Wannarka GL, Mesa M, Andrews P, Pellock J. Pharmacokinetics of diazepam administered intramuscularly by autoinjector versus rectal gel in healthy subjects: a phase I, randomized, open-label, single-dose, crossover, single-centre study. Clin Drug Investig. 2011;31(8):585–97.PubMedCrossRef
102.
Henney HR 3rd, Sperling MR, Rabinowicz AL, Bream G, Carrazana EJ. Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults. Epilepsy Res. 2014;108(7):1204–11.PubMedCrossRef
103.
Abou-Khalil B, Wheless J, Rogin J, Wolter KD, Pixton GC, Shukla RB, et al. A double-blind, randomized, placebo-controlled trial of a diazepam auto-injector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures. Epilepsia. 2013;54(11):1968–76.PubMedCrossRef
104.
Rogin J, Wheless J, Abou-Khalil B, Wolter KD, Pixton GC, Sherman NA, et al. Safety and effectiveness of long-term treatment with diazepam auto-injector administered by caregivers in an outpatient setting for the treatment of acute repetitive seizures. Epilepsia. 2014;55(9):1444–51.PubMedCrossRef
105.
Cereghino JJ, Cloyd JC, Kuzniecky RI. North American Diastat Study G Rectal diazepam gel for treatment of acute repetitive seizures in adults. Arch Neurol. 2002;59(12):1915–20.PubMedCrossRef
106.
Pellock JM. Treatment of seizures and epilepsy in children and adolescents. Neurology. 1998;51(5 Suppl 4):S8-14.PubMedCrossRef
107.
Fakhoury T, Chumley A, Bensalem-Owen M. Effectiveness of diazepam rectal gel in adults with acute repetitive seizures and prolonged seizures: a single-centre experience. Epilepsy Behav. 2007;11(3):357–60.PubMedCrossRef
108.
Remy C, Jourdil N, Villemain D, Favel P, Genton P. Intrarectal diazepam in epileptic adults. Epilepsia. 1992;33(2):353–8.PubMedCrossRef
109.
Mitchell WG, Conry JA, Crumrine PK, Kriel RL, Cereghino JJ, Groves L, et al. An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance North American Diastat Group. Epilepsia. 1999;40(11):1610–7.PubMedCrossRef
110.
Milligan NM, Dhillon S, Griffiths A, Oxley J, Richens A. A clinical trial of single dose rectal and oral administration of diazepam for the prevention of serial seizures in adult epileptic patients. J Neurol Neurosurg Psychiatry. 1984;47(3):235–40.PubMedPubMedCentralCrossRef
111.
Smith BT, Masotti RE. Intravenous diazepam in the treatment of prolonged seizure activity in neonates and infants. Dev Med Child Neurol. 1971;13(5):630–4.PubMedCrossRef
112.
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.PubMedCrossRef
113.
Singhi S, Banerjee S, Singhi P. Refractory status epilepticus in children: role of continuous diazepam infusion. J Child Neurol. 1998;13(1):23–6.PubMedCrossRef
114.
Henriksen PB. Acute treatment of epileptic seizures with diazepamum (Valium). Acta Neurol Scand. 1967;43(S31):168–9.PubMedCrossRef
115.
Hoppu K, Santavuori P. Diazepam rectal solution for home treatment of acute seizures in children. Acta Paediatr Scand. 1981;70(3):369–72.PubMedCrossRef
116.
Chen WB, Gao R, Su YY, Zhao JW, Zhang YZ, Wang L, et al. Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study. Eur J Neurol. 2011;18(12):1391–6.PubMedCrossRef
117.
Mehta V, Singhi P, Singhi S. Intravenous sodium valproate versus diazepam infusion for the control of refractory status epilepticus in children: a randomized controlled trial. J Child Neurol. 2007;22(10):1191–7.PubMedCrossRef
118.
Singhi S, Murthy A, Singhi P, Jayashree M. Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus. J Child Neurol. 2002;17(2):106–10.PubMedCrossRef
119.
Tang RH, Zhou JB. A control study on the treatment of acute seizures with midazolam and diazepam in children. Zhongguo Dang Dai Er Ke Za Zhi. 2010;12(7):530–2.PubMed
120.
Gathwala G, Goel M, Singh J, Mittal K. Intravenous diazepam, midazolam and lorazepam in acute seizure control. Indian J Pediatr. 2012;79(3):327–32.PubMedCrossRef
121.
Sreenath TG, Gupta P, Sharma KK, Krishnamurthy S. Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children: a randomized controlled trial. Eur J Paediatr Neurol. 2010;14(2):162–8.PubMedCrossRef
122.
Shaner DM, McCurdy SA, Herring MO, Gabor AJ. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology. 1988;38(2):202–7.PubMedCrossRef
123.
Shah I, Deshmukh CT. Intramuscular midazolam vs intravenous diazepam for acute seizures. Indian J Pediatr. 2005;72(8):667–70.PubMedCrossRef
124.
Portela JL, Garcia PC, Piva JP, Barcelos A, Bruno F, Branco R, et al. Intramuscular midazolam versus intravenous diazepam for treatment of seizures in the paediatric emergency department: a randomized clinical trial. Med Intensiva. 2015;39(3):160–6.PubMedCrossRef
125.
Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000;321(7253):83–6.PubMedPubMedCentralCrossRef
126.
Mahmoudian T, Zadeh MM. Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav. 2004;5(2):253–5.PubMedCrossRef
127.
Javadzadeh M, Sheibani K, Hashemieh M, Saneifard H. Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial. Iran J Pediatr. 2012;22(1):1–8.PubMedPubMedCentral
128.
Talukdar B, Chakrabarty B. Efficacy of buccal midazolam compared to intravenous diazepam in controlling convulsions in children: a randomized controlled trial. Brain Dev. 2009;31(10):744–9.PubMedCrossRef
129.
Tonekaboni SH, Shamsabadi FM, Anvari SS, Mazrooei A, Ghofrani M. A comparison of buccal midazolam and intravenous diazepam for the acute treatment of seizures in children. Iran J Pediatr. 2012;22(3):303–8.PubMedPubMedCentral
130.
Mittal P, Manohar R, Rawat AK. Comparative study of intranasal midazolam and intravenous diazepam sedation for procedures and seizures. Indian J Pediatr. 2006;73(11):975–8.PubMedCrossRef
131.
Mpimbaza A, Ndeezi G, Staedke S, Rosenthal PJ, Byarugaba J. Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics. 2008;121(1):e58-64.PubMedCrossRef
132.
Ashrafi MR, Khosroshahi N, Karimi P, Malamiri RA, Bavarian B, Zarch AV, et al. Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children. Eur J Paediatr Neurol. 2010;14(5):434–8.PubMedCrossRef
133.
Baysun S, Aydin OF, Atmaca E, Gurer YK. A comparison of buccal midazolam and rectal diazepam for the acute treatment of seizures. Clin Pediatr (Phila). 2005;44(9):771–6.PubMedCrossRef
134.
Fisgin T, Gurer Y, Tezic T, Senbil N, Zorlu P, Okuyaz C, et al. Effects of intranasal midazolam and rectal diazepam on acute convulsions in children: prospective randomized study. J Child Neurol. 2002;17(2):123–6.PubMedCrossRef
135.
Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol. 2006;34(5):355–9.PubMedCrossRef
136.
Trajano M, Sanchez B, Lukban M, Salonga A. PO18WE40 Buccal midazolam compared to rectal diazepam and intravenous midazolam as emergent treatment of acute seizures in children: preliminary study. J Neurol Sci. 2009;S255.
137.
Malu CK, Kahamba DM, Walker TD, Mukampunga C, Musalu EM, Kokolomani J, et al. Efficacy of sublingual lorazepam versus intrarectal diazepam for prolonged convulsions in Sub-Saharan Africa. J Child Neurol. 2014;29(7):895–902.PubMedCrossRef
138.
Sirsi D. Is intranasal midazolam better than rectal diazepam for home management of acute seizures? Arch Neurol. 2011;68(1):120–1.PubMedCrossRef
139.
Chamberlain DB, Chamberlain JM. Making sense of a negative clinical trial result: a bayesian analysis of a clinical trial of lorazepam and diazepam for pediatric status epilepticus. Ann Emerg Med. 2017;69(1):117–24.PubMedCrossRef
140.
Meierkord H, Boon P, Engelsen B, Gocke K, Shorvon S, Tinuper P, et al. EFNS guideline on the management of status epilepticus in adults. Eur J Neurol. 2010;17(3):348–55.PubMedCrossRef
141.
Congdon PJ, Forsythe WI. Intravenous clonazepam in the treatment of status epilepticus in children. Epilepsia. 1980;21(1):97–102.PubMedCrossRef
142.
Gastaut H, Courjon J, Poire R, Weber M. Treatment of status epilepticus with a new benzodiazepine more active than diazepam. Epilepsia. 1971;12(3):197–214.PubMedCrossRef
143.
Navarro V, Dagron C, Elie C, Lamhaut L, Demeret S, Urien S, et al. Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2016;15(1):47–55.PubMedCrossRef
144.
Pinder RM, Brogden RN, Speight TM, Avery GS. Clonazepam: a review of its pharmacological properties and therapeutic efficacy in epilepsy. Drugs. 1976;12(5):321–61.PubMedCrossRef
145.
Rantsch K, Walter U, Wittstock M, Benecke R, Rosche J. Treatment and course of different subtypes of status epilepticus. Epilepsy Res. 2013;107(1–2):156–62.PubMedCrossRef
146.
Singh AN, Le Morvan P. Treatment of status epilepticus with intravenous clonazepam. Prog Neuropsychopharmacol Biol Psychiatry. 1982;6(4–6):539–42.PubMedCrossRef
147.
Sorel L, Mechler L, Harmant J. Comparative trial of intravenous lorazepam and clonazepam im status epilepticus. Clin Ther. 1981;4(4):326–36.PubMed
148.
Troester MM, Hastriter EV, Ng YT. Dissolving oral clonazepam wafers in the acute treatment of prolonged seizures. J Child Neurol. 2010;25(12):1468–72.PubMedCrossRef
149.
Abdel-Bar HM, Abdel-Reheem AY, Awad GA, Mortada ND. Evaluation of brain targeting and mucosal integrity of nasally administrated nanostructured carriers of a CNS active drug, clonazepam. J Pharm Pharm Sci. 2013;16(3):456–69.PubMedCrossRef
150.
Rylance GW, Poulton J, Cherry RC, Cullen RE. Plasma concentrations of clonazepam after single rectal administration. Arch Dis Child. 1986;61(2):186–8.PubMedPubMedCentralCrossRef
151.
Crevoisier C, Delisle MC, Joseph I, Foletti G. Comparative single-dose pharmacokinetics of clonazepam following intravenous, intramuscular and oral administration to healthy volunteers. Eur Neurol. 2003;49(3):173–7.PubMedCrossRef
152.
Sakata O, Onishi H, Machida Y. Clonazepam oral droplets for the treatment of acute epileptic seizures. Drug Dev Ind Pharm. 2008;34(12):1376–80.PubMedCrossRef
153.
Greenblatt DJ, Blaskovich PD, Nuwayser ES, Harmatz JS, Chen G, Zinny MA. Clonazepam pharmacokinetics: comparison of subcutaneous microsphere injection with multiple-dose oral administration. J Clin Pharmacol. 2005;45(11):1288–93.PubMedCrossRef
154.
Roche. KLONOPIN TABLETS (clonazepam), KLONOPIN WAFERS (clonazepam orally desintegrating tablets). https://​www.​accessdata.​fda.​gov/​drugsatfda_​docs/​label/​2009/​017533s045,020813s005lbl.pdf.
155.
Seree EJ, Pisano PJ, Placidi M, Rahmani R, Barra YA. Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. Fundam Clin Pharmacol. 1993;7(2):69–75.PubMedCrossRef
156.
Greenblatt DJ, Ehrenberg BL, Gunderman J, Locniskar A, Scavone JM, Harmatz JS, et al. Pharmacokinetic and electroencephalographic study of intravenous diazepam, midazolam, and placebo. Clin Pharmacol Ther. 1989;45(4):356–65.PubMedCrossRef
157.
Greenblatt DJ, Ehrenberg BL, Gunderman J, Scavone JM, Tai NT, Harmatz JS, et al. Kinetic and dynamic study of intravenous lorazepam: comparison with intravenous diazepam. J Pharmacol Exp Ther. 1989;250(1):134–40.PubMed
158.
Greenblatt DJ, Sethy VH. Benzodiazepine concentrations in brain directly reflect receptor occupancy: studies of diazepam, lorazepam, and oxazepam. Psychopharmacology. 1990;102(3):373–8.PubMedCrossRef
159.
Semmlack S, Tschudin-Sutter S, Widmer AF, Valenca M, Ruegg S, Marsch S, et al. Independent impact of infections on the course and outcome of status epilepticus: a 10-year cohort study. J Neurol. 2016;263(7):1303–13.PubMedCrossRef
160.
Sutter R, Tschudin-Sutter S, Grize L, Fuhr P, Bonten MJ, Widmer AF, et al. Associations between infections and clinical outcome parameters in status epilepticus: a retrospective 5-year cohort study. Epilepsia. 2012;53(9):1489–97.PubMedCrossRef
161.
Guterman EL, Betjemann JP, Aimetti A, Li JW, Wang Z, Yin D, et al. Association between treatment progression, disease refractoriness, and burden of illness among hospitalized patients with status epilepticus. JAMA Neurol. 2021;78(5):588–95.PubMedCrossRef
162.
Keating GM. Loxapine inhalation powder: a review of its use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. CNS Drugs. 2013;27(6):479–89.PubMedCrossRef
163.
Grosset KA, Malek N, Morgan F, Grosset DG. Inhaled apomorphine in patients with “on-off” fluctuations: a randomized, double-blind, placebo-controlled, clinic and home based, parallel-group study. J Parkinsons Dis. 2013;3(1):31–7.PubMedCrossRef
164.
French JA, Wechsler R, Gelfand MA, Pollard JR, Vazquez B, Friedman D, et al. Inhaled alprazolam rapidly suppresses epileptic activity in photosensitive participants. Epilepsia. 2019;60(8):1602–9.PubMedCrossRef
165.
Xi LY, Zheng WM, Zhen SM, Xian NS. Rapid arrest of seizures with an inhalation aerosol containing diazepam. Epilepsia. 1994;35(2):356–8.PubMedCrossRef
166.
Dhir A, Zolkowska D, Murphy RB, Rogawski MA. Seizure protection by intrapulmonary delivery of propofol hemisuccinate. J Pharmacol Exp Ther. 2011;336(1):215–22.PubMedCrossRef
167.
Dhir A, Zolkowska D, Rogawski MA. Seizure protection by intrapulmonary delivery of midazolam in mice. Neuropharmacology. 2013;73:425–31.PubMedCrossRef
168.
169.
Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP. Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology. 1984;84(4):452–6.PubMedCrossRef
170.
Huybrechts I. The pharmacology of alprazolam: a review. Clin Ther. 1991;13(1):100–17.PubMed
171.
FDA. XANAX® - FDA label. Reference ID: 3004871: Food And Drug Administration (FDA); 2011.
172.
Anderson GD. Children versus adults: pharmacokinetic and adverse-effect differences. Epilepsia. 2002;43(Suppl 3):53–9.PubMedCrossRef
173.
Morselli PL, Principi N, Tognoni G, Reali E, Belvedere G, Standen SM, et al. Diazepam elimination in premature and full term infants, and children. J Perinat Med. 1973;1(2):133–41.PubMedCrossRef
174.
Blumer JL. Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet. 1998;35(1):37–47.PubMedCrossRef
175.
Gonzalez D, Chamberlain JM, Guptill JT, Cohen-Wolkowiez M, Harper B, Zhao J, et al. Population pharmacokinetics and exploratory pharmacodynamics of lorazepam in pediatric status epilepticus. Clin Pharmacokinet. 2017;56(8):941–51.PubMedPubMedCentralCrossRef
176.
Chamberlain JM, Capparelli EV, Brown KM, Vance CW, Lillis K, Mahajan P, et al. Pharmacokinetics of intravenous lorazepam in paediatric patients with and without status epilepticus. J Pediatr. 2012;160(4):667–72.PubMedCrossRef
177.
European Medicines Agency. European Medicines Agency Committee for Medicinal Products for Human Use assessment report for Buccolam® (buccal midazolam); 2011.
178.
Garnock-Jones KP. Oromucosal midazolam: a review of its use in paediatric patients with prolonged acute convulsive seizures. Paediatr Drugs. 2012;14(4):251–61.PubMedCrossRef
179.
180.
Rogalski R, Rogalski A. Benzodiazepine selection in the management of status epilepticus: a review. Adv Emerg Nurs J. 2015;37(2):83–94.PubMedCrossRef
181.
182.
Der-Nigoghossian C, Rubinos C, Alkhachroum A, Claassen J. Status epilepticus—time is brain and treatment considerations. Curr Opin Crit Care. 2019;25(6):638–46.PubMedPubMedCentralCrossRef
183.
Wermeling DP, Miller JL, Archer SM, Manaligod JM, Rudy AC. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol. 2001;41(11):1225–31.PubMedCrossRef
184.
Lau CE, Ma F, Wang Y, Smith C. Pharmacokinetics and bioavailability of midazolam after intravenous, subcutaneous, intraperitoneal and oral administration under a chronic food-limited regimen: relating DRL performance to pharmacokinetics. Psychopharmacology. 1996;126(3):241–8.PubMedCrossRef
185.
Shangguan Y, Liao H, Wang X. Clonazepam in the treatment of status epilepticus. Expert Rev Neurother. 2015;15(7):733–40.PubMedCrossRef
186.
Hogan RE, Gidal BE, Koplowitz B, Koplowitz LP, Lowenthal RE, Carrazana E. Bioavailability and safety of diazepam intranasal solution compared to oral and rectal diazepam in healthy volunteers. Epilepsia. 2020;61(3):455–64.PubMedPubMedCentralCrossRef
187.
Ahmad S, Ellis JC, Kamwendo H, Molyneux E. Efficacy and safety of intranasal lorazepam versus intramuscular paraldehyde for protracted convulsions in children: an open randomised trial. Lancet. 2006;367(9522):1591–7.PubMedCrossRef
188.
Jeannet PY, Roulet E, Maeder-Ingvar M, Gehri M, Jutzi A, Deonna T. Home and hospital treatment of acute seizures in children with nasal midazolam. Eur J Paediatr Neurol. 1999;3(2):73–7.PubMedCrossRef
189.
Kazmi A, Abbas G, Khurshid A, Sahr S, Malhi T, Hanif M, et al. A comparison of intravenous midazolam and diazepam in management of status epilepticus in children. J Pak Med Assoc. 2020;2:1–13.
190.
Kutlu NO, Dogrul M, Yakinci C, Soylu H. Buccal midazolam for treatment of prolonged seizures in children. Brain Dev. 2003;25(4):275–8.PubMedCrossRef
191.
192.
Lacey DJ, Singer WD, Horwitz SJ, Gilmore H. Lorazepam therapy of status epilepticus in children and adolescents. J Pediatr. 1986;108(5 Pt 1):771–4.PubMedCrossRef
193.
Crawford TO, Mitchell WG, Snodgrass SR. Lorazepam in childhood status epilepticus and serial seizures: effectiveness and tachyphylaxis. Neurology. 1987;37(2):190–5.PubMedCrossRef
194.
Giang DW, McBride MC. Lorazepam versus diazepam for the treatment of status epilepticus. Pediatr Neurol. 1988;4(6):358–61.PubMedCrossRef
195.
Misra UK, Kalita J, Maurya PK. Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled pilot study. J Neurol. 2012;259(4):645–8.PubMedCrossRef
196.
Chin RF, Neville BG, Peckham C, Wade A, Bedford H, Scott RC. Treatment of community-onset, childhood convulsive status epilepticus: a prospective, population-based study. Lancet Neurol. 2008;7(8):696–703.PubMedPubMedCentralCrossRef
197.
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.PubMedPubMedCentralCrossRef
198.
Gathwala G, Goel M, Singh J, Mittal K. Intravenous diazepam, midazolam and lorazepam in acute seizure control. Indian J Pediatr. 2012;79:327–32.PubMedCrossRef
199.
Bergamini L, Mutani R, Fariello R, Liboni W, Quattrocolo GL. Action du Ro 5 ⁄ 4023 dans le traitement des differentes formes d epilepsie. Paper given at the Rivotril Symposium, Marseilles, France. 1972.
200.
Bergamini L, Mutani R, Liboni W. Elektroenzephalographische und klinische Bewertung des neuen Benzodiazepin Ro 5 ⁄ 4023. EEG EMG. 1970;1:182–8.
201.
Gimenez-Roldan S, Lopez Agreda J, Martin F. Un nuevo medicamento eficaz en el trataimento del status epilepticus - Ro 5-4023. Med Clin (Barc). 1972;58(133).
202.
Beck H, Tousche C. Traitement des etats de mal epileptiques par le clonazepam Sem Hop Paris. 1973;49(21).
203.
Bladin PF. The use of clonazepam as an anticonvulsant–clinical evaluation. Med J Aust. 1973;1(14):683–8.PubMedCrossRef
204.
Ketz E, Bernoulli C, Siegfried J. Clinical and electroencephalographic trial with clonazepam (Ro 5–4023) with special regard to status epilepticus. Acta Neurol Scand Suppl. 1973;53:47–53.PubMed
205.
Kruse R, Blankenhorn V. Clinical use and effect of Ro 5–4023 (clonazepam) in different forms of epileptic seizures. Acta Neurol Scand Suppl. 1973;53:60–71.PubMed
206.
Martin D, Hirt H. Clinical experience with clonazepam (Rivotril) in the treatment of epilepsies in infancy and childhood. Neuropaediatrics. 1973;4:245–66.CrossRef
207.
Tridon P, Weber M. Conduite du traitement des etats de mal epileptiques par le Ro. Sem Hop Paris. 1973;49:29.
Metadata
Title
Benzodiazepines in the Management of Seizures and Status Epilepticus: A Review of Routes of Delivery, Pharmacokinetics, Efficacy, and Tolerability
Authors
Ricardo Kienitz
Lara Kay
Isabelle Beuchat
Sarah Gelhard
Sophie von Brauchitsch
Catrin Mann
Alexandra Lucaciu
Jan-Hendrik Schäfer
Kai Siebenbrodt
Johann-Philipp Zöllner
Susanne Schubert-Bast
Felix Rosenow
Adam Strzelczyk
Laurent M. Willems
Publication date
01-09-2022
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 9/2022
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-022-00940-2

Other articles of this Issue 9/2022

CNS Drugs 9/2022 Go to the issue

Adis Drug Evaluation

Onasemnogene Abeparvovec: A Review in Spinal Muscular Atrophy

AdisInsight Report

Sodium Phenylbutyrate and Ursodoxicoltaurine: First Approval

Original Research Article

Improvements in Cognitive Processing Speed, Disability, and Patient-Reported Outcomes in Patients with Early Relapsing-Remitting Multiple Sclerosis Treated with Natalizumab: Results of a 4-year, Real-World, Open-Label Study

Current Opinion

Treatment Options in Refractory Autoimmune Encephalitis

Correction

Correction: A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

Review Article

New Oral Drugs for Migraine