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 3/2018

01-03-2018 | Review Article

Newer Antiepileptic Drugs for Status Epilepticus in Adults: What’s the Evidence?

Authors: Isabelle Beuchat, Jan Novy, Andrea O. Rossetti

Published in: CNS Drugs | Issue 3/2018

Login to get access

Abstract

Status epilepticus (SE) is one of the most frequent neurological emergencies. Despite this, understanding of its pathophysiology and evidence regarding its management is limited. Rapid, effective, and well-tolerated treatment to achieve seizure cessation is advocated to prevent brain damage or potentially lethal outcomes. The last two decades have witnessed an exponential increase in the number of available antiepileptic drugs (AEDs). These compounds, especially lacosamide and levetiracetam, in view of their intravenous formulation, have been increasingly prescribed in SE. These and other newer AEDs present a promising profile in terms of tolerability, with few centrally depressive effects, favorable pharmacokinetic properties, and fewer drug interactions than classical AEDs; conversely, they are more expensive. There is still no clear evidence to suggest a specific beneficial impact of newer AEDs on SE outcome, preventing any strong recommendation regarding their prescription in SE. Further comparative studies are urgently required to clarify their place and optimal use in the armamentarium of SE treatment.
Literature
1.
2.
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.CrossRefPubMed
3.
Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia. 1999;40(1):120–2.CrossRefPubMed
4.
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.CrossRefPubMed
5.
Delaj L, Novy J, Ryvlin P, Marchi NA, Rossetti AO. Refractory and super-refractory status epilepticus in adults: a 9-year cohort study. Acta Neurol Scand. 2017;135(1):92–9.CrossRefPubMed
6.
Beuchat I, Novy J, Rossetti AO. Newer antiepileptic drugs in status epilepticus: prescription trends and outcomes in comparison with traditional agents. CNS Drugs. 2017;31(4):327–34.CrossRefPubMed
7.
Jaques L, Rossetti AO. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis. Epilepsy Behav E&B. 2012;24(1):70–3.CrossRef
8.
Rossetti AO. Are newer AEDs better than the classic ones in the treatment of status epilepticus? J Clin Neurophysiol. 2016;33(1):18–21.CrossRefPubMed
9.
Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2013;54(3):551–63.CrossRefPubMed
10.
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3–23.CrossRefPubMed
11.
Claassen J, Riviello JJ Jr, Silbergleit R. Emergency neurological life support: status epilepticus. Neurocrit Care. 2015;23(Suppl 2):S136–42.CrossRefPubMed
12.
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/Am Epilepsy Soc. 2016;16(1):48–61.CrossRef
13.
Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies. Seizure J Br Epilepsy Assoc. 2014;23(3):167–74.CrossRef
14.
Misra UK, Kalita J. A comparison of four antiepileptic drugs in status epilepticus: experience from India. Int J Neurosci. 2016;126(11):1013–9.CrossRefPubMed
15.
Knake S, Gruener J, Hattemer K, Klein KM, Bauer S, Oertel WH, et al. Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J Neurol Neurosurg Psychiatry. 2008;79(5):588–9.CrossRefPubMed
16.
Rossetti AO, Bromfield EB. Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes. Eur Neurol. 2005;54(1):34–8.CrossRefPubMed
17.
Ruegg S, Naegelin Y, Hardmeier M, Winkler DT, Marsch S, Fuhr P. Intravenous levetiracetam: Treatment experience with the first 50 critically ill patients. Epilepsy Behav E&B. 2008;12(3):477–80.CrossRef
18.
Ramael S, Daoust A, Otoul C, Toublanc N, Troenaru M, Lu ZS, et al. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia. 2006;47(7):1128–35.CrossRefPubMed
19.
Ramael S, De Smedt F, Toublanc N, Otoul C, Boulanger P, Riethuisen JM, et al. Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin Ther. 2006;28(5):734–44.CrossRefPubMed
20.
Trinka E. What is the evidence to use new intravenous AEDs in status epilepticus? Epilepsia. 2011;52(Suppl 8):35–8.CrossRefPubMed
21.
Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther Adv Neurol Disord. 2009;2(2):79–91.CrossRefPubMedPubMedCentral
22.
Chakravarthi S, Goyal MK, Modi M, Bhalla A, Singh P. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015;22(6):959–63.CrossRefPubMed
23.
Gujjar AR, Nandhagopal R, Jacob PC, Al-Hashim A, Al-Amrani K, Ganguly SS, et al. Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: a prospective, randomized study. Seizure. 2017;49:8–12.CrossRefPubMed
24.
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.CrossRefPubMed
25.
Mundlamuri RC, Sinha S, Subbakrishna DK, Prathyusha PV, Nagappa M, Bindu PS, et al. Management of generalised convulsive status epilepticus (SE): a prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam—pilot study. Epilepsy Res. 2015;114:52–8.CrossRefPubMed
26.
Brigo F, Bragazzi N, Nardone R, Trinka E. Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus. Epilepsy Behav. 2016;64(Pt A):110–5.
27.
Zelano J, Kumlien E. Levetiracetam as alternative stage two antiepileptic drug in status epilepticus: a systematic review. Seizure. 2012;21(4):233–6.CrossRefPubMed
28.
Alvarez V, Januel JM, Burnand B, Rossetti AO. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011;52(7):1292–6.CrossRefPubMed
29.
Eue S, Grumbt M, Muller M, Schulze A. Two years of experience in the treatment of status epilepticus with intravenous levetiracetam. Epilepsy Behav. 2009;15(4):467–9.CrossRefPubMed
30.
De Smedt T, Raedt R, Vonck K, Boon P. Levetiracetam: part II, the clinical profile of a novel anticonvulsant drug. CNS Drug Rev. 2007;13(1):57–78.CrossRefPubMed
31.
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.CrossRefPubMed
32.
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016;57(2):201–9.CrossRefPubMed
33.
Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet. 2015;54(9):901–14.CrossRefPubMed
34.
Cawello W, Stockis A, Andreas JO, Dimova S. Advances in epilepsy treatment: lacosamide pharmacokinetic profile. Ann N Y Acad Sci. 2014;1329:18–32.CrossRefPubMed
35.
Chung SS. Lacosamide: new adjunctive treatment option for partial-onset seizures. Expert Opin Pharmacother. 2010;11(9):1595–602.CrossRefPubMed
36.
Kellinghaus C. Lacosamide as treatment for partial epilepsy: mechanisms of action, pharmacology, effects, and safety. Ther Clin Risk Manag. 2009;5:757–66.CrossRefPubMedPubMedCentral
37.
Brigo F, Trinka E. Randomized controlled trials in status epilepticus: Size matters. Epilepsia. 2017;58(5):915.CrossRefPubMed
38.
Misra UK, Dubey D, Kalita J. A randomized controlled trial of lacosamide versus sodium valproate in status epilepticus. Epilepsia. 2017.
39.
Hofler J, Trinka E. Lacosamide as a new treatment option in status epilepticus. Epilepsia. 2013;54(3):393–404.CrossRefPubMed
40.
Strzelczyk A, Zollner JP, Willems LM, Jost J, Paule E, Schubert-Bast S, et al. Lacosamide in status epilepticus: systematic review of current evidence. Epilepsia. 2017;58(6):933–50.CrossRefPubMed
41.
Kellinghaus C, Berning S, Stogbauer F. Intravenous lacosamide or phenytoin for treatment of refractory status epilepticus. Acta Neurol Scand. 2014;129(5):294–9.CrossRefPubMed
42.
Sutter R, Marsch S, Ruegg S. Safety and efficacy of intravenous lacosamide for adjunctive treatment of refractory status epilepticus: a comparative cohort study. CNS Drugs. 2013;27(4):321–9.CrossRefPubMed
43.
Belcastro V, Vidale S, Pierguidi L, Sironi L, Tancredi L, Striano P, et al. Intravenous lacosamide as treatment option in post-stroke non convulsive status epilepticus in the elderly: a proof-of-concept, observational study. Seizure. 2013;22(10):905–7.CrossRefPubMed
44.
Miro J, Toledo M, Santamarina E, Ricciardi AC, Villanueva V, Pato A, et al. Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: a multicentric prospective study. Seizure J Br Epilepsy Assoc. 2013;22(1):77–9.CrossRef
45.
Kellinghaus C, Berning S, Immisch I, Larch J, Rosenow F, Rossetti AO, et al. Intravenous lacosamide for treatment of status epilepticus. Acta Neurol Scand. 2011;123(2):137–41.CrossRefPubMed
46.
Santamarina E, Toledo M, Sueiras M, Raspall M, Ailouti N, Lainez E, et al. Usefulness of intravenous lacosamide in status epilepticus. J Neurol. 2013;260(12):3122–8.CrossRefPubMed
47.
Garces M, Villanueva V, Mauri JA, Suller A, Garcia C, Lopez Gonzalez FJ, et al. Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study. Epilepsy Behav. 2014;36:144–52.CrossRefPubMed
48.
Hofler J, Unterberger I, Dobesberger J, Kuchukhidze G, Walser G, Trinka E. Intravenous lacosamide in status epilepticus and seizure clusters. Epilepsia. 2011;52(10):e148–52.CrossRefPubMed
49.
Goodwin H, Hinson HE, Shermock KM, Karanjia N, Lewin JJ 3rd. The use of lacosamide in refractory status epilepticus. Neurocrit Care. 2011;14(3):348–53.CrossRefPubMed
50.
Legros B, Depondt C, Levy-Nogueira M, Ligot N, Mavroudakis N, Naeije G, et al. Intravenous lacosamide in refractory seizure clusters and status epilepticus: comparison of 200 and 400 mg loading doses. Neurocrit Care. 2014;20(3):484–8.CrossRefPubMed
51.
Perrenoud M, Andre P, Alvarez V, Stahli C, Decosterd LA, Rossetti AO, et al. Intravenous lacosamide in status epilepticus: correlation between loading dose, serum levels, and clinical response. Epilepsy Res. 2017;135:38–42.CrossRefPubMed
52.
Gillard M, Fuks B, Leclercq K, Matagne A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol. 2011;664(1–3):36–44.CrossRefPubMed
53.
Niquet J, Suchomelova L, Thompson K, Klitgaard H, Matagne A, Wasterlain C. Acute and long-term effects of brivaracetam and brivaracetam-diazepam combinations in an experimental model of status epilepticus. Epilepsia. 2017;58(7):1199–207.CrossRefPubMed
54.
Wasterlain CG, Baldwin R, Naylor DE, Thompson KW, Suchomelova L, Niquet J. Rational polytherapy in the treatment of acute seizures and status epilepticus. Epilepsia. 2011;52(Suppl 8):70–1.CrossRefPubMedPubMedCentral
55.
Strzelczyk A, Steinig I, Willems LM, Reif PS, Senft C, Voss M, et al. Treatment of refractory and super-refractory status epilepticus with brivaracetam: a cohort study from two German university hospitals. Epilepsy Behav. 2017;70(Pt A):177–81.
56.
Kalss GRA, Leitinger M, Georg P, Novak H, Neuray C, Kreidenhuber R, Höfler J, Kuchukhidze G, Trinka E. Intravenous Brivaracetam in Status epilepticus—a retrospectie single centre study. Epilepsia. 2018 (in press).
57.
Novy J, Logroscino G, Rossetti AO. Refractory status epilepticus: a prospective observational study. Epilepsia. 2010;51(2):251–6.CrossRefPubMed
58.
59.
Bensalem MK, Fakhoury TA. Topiramate and status epilepticus: report of three cases. Epilepsy Behav. 2003;4(6):757–60.CrossRefPubMed
60.
Hottinger A, Sutter R, Marsch S, Ruegg S. Topiramate as an adjunctive treatment in patients with refractory status epilepticus: an observational cohort study. CNS Drugs. 2012;26(9):761–72.CrossRefPubMed
61.
Stojanova V, Rossetti AO. Oral topiramate as an add-on treatment for refractory status epilepticus. Acta Neurol Scand. 2012;125(2):e7–11.CrossRefPubMed
62.
Synowiec AS, Yandora KA, Yenugadhati V, Valeriano JP, Schramke CJ, Kelly KM. The efficacy of topiramate in adult refractory status epilepticus: experience of a tertiary care center. Epilepsy Res. 2012;98(2–3):232–7.CrossRefPubMed
63.
Towne AR, Garnett LK, Waterhouse EJ, Morton LD, DeLorenzo RJ. The use of topiramate in refractory status epilepticus. Neurology. 2003;60(2):332–4.CrossRefPubMed
64.
Madzar D, Kuramatsu JB, Gerner ST, Huttner HB. Assessing the value of topiramate in refractory status epilepticus. Seizure. 2016;38:7–10.CrossRefPubMed
65.
Novy J, Rossetti AO. Oral pregabalin as an add-on treatment for status epilepticus. Epilepsia. 2010;51(10):2207–10.CrossRefPubMed
66.
Swisher CB, Doreswamy M, Husain AM. Use of pregabalin for nonconvulsive seizures and nonconvulsive status epilepticus. Seizure. 2013;22(2):116–8.CrossRefPubMed
67.
Chen JW, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006;5(3):246–56.CrossRefPubMed
68.
Naylor DE, Liu H, Wasterlain CG. Trafficking of GABA(A) receptors, loss of inhibition, and a mechanism for pharmacoresistance in status epilepticus. J Neurosci. 2005;25(34):7724–33.CrossRefPubMed
69.
Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: a novel noncompetitive AMPA receptor antagonist. Epilepsia. 2015;56(1):12–27.CrossRefPubMed
70.
Redecker J, Wittstock M, Benecke R, Rosche J. Efficacy of perampanel in refractory nonconvulsive status epilepticus and simple partial status epilepticus. Epilepsy Behav. 2015;45:176–9.CrossRefPubMed
71.
Rohracher A, Hofler J, Kalss G, Leitinger M, Kuchukhidze G, Deak I, et al. Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit. Epilepsy Behav. 2015;49:354–8.CrossRefPubMed
72.
Rosche J, Kampf C, Benecke R. Possible effect of perampanel on focal status epilepticus after generalized tonic-clonic status epilepticus. Acta Neurol Belg. 2014;114(3):243–4.CrossRefPubMed
73.
Santamarina E, Sueiras M, Lidon RM, Guzman L, Baneras J, Gonzalez M, et al. Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report. Epilepsy Behav Case Rep. 2015;4:56–9.CrossRefPubMedPubMedCentral
74.
75.
Thakur KT, Probasco JC, Hocker SE, Roehl K, Henry B, Kossoff EH, et al. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014;82(8):665–70.CrossRefPubMedPubMedCentral
76.
Strzelczyk A, Kortland LM, Knake S, Rosenow F. Stiripentol for the treatment of super-refractory status epilepticus. Acta Neurol Scand. 2015;132(6):435–9.CrossRefPubMed
77.
78.
Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, et al. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017;82(3):342–52.CrossRefPubMedPubMedCentral
79.
Erstad BL, Patanwala AE. Ketamine for analgosedation in critically ill patients. J Crit Care. 2016;35:145–9.CrossRefPubMed
80.
Gaspard N, Foreman B, Judd LM, Brenton JN, Nathan BR, McCoy BM, et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013;54(8):1498–503.CrossRefPubMedPubMedCentral
81.
Litt B, Wityk RJ, Hertz SH, Mullen PD, Weiss H, Ryan DD, et al. Nonconvulsive status epilepticus in the critically ill elderly. Epilepsia. 1998;39(11):1194–202.CrossRefPubMed
82.
Marchi NA, Novy J, Faouzi M, Stahli C, Burnand B, Rossetti AO. Status epilepticus: impact of therapeutic coma on outcome. Crit Care Med. 2015;43(5):1003–9.CrossRefPubMed
83.
Sutter R, Marsch S, Fuhr P, Kaplan PW, Ruegg S. Anesthetic drugs in status epilepticus: risk or rescue? A 6-year cohort study. Neurology. 2014;82(8):656–64.CrossRefPubMedPubMedCentral
84.
Logroscino G, Hesdorffer DC, Cascino G, Annegers JF, Hauser WA. Short-term mortality after a first episode of status epilepticus. Epilepsia. 1997;38(12):1344–9.CrossRefPubMed
85.
Rossetti AO, Alvarez V, Januel JM, Burnand B. Treatment deviating from guidelines does not influence status epilepticus prognosis. J Neurol. 2013;260(2):421–8.CrossRefPubMed
86.
Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia. 1994;35(1):27–34.CrossRefPubMed
87.
Rossetti AO, Hurwitz S, Logroscino G, Bromfield EB. Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation. J Neurol Neurosurg Psychiatry. 2006;77(5):611–5.CrossRefPubMedPubMedCentral
88.
Metadata
Title
Newer Antiepileptic Drugs for Status Epilepticus in Adults: What’s the Evidence?
Authors
Isabelle Beuchat
Jan Novy
Andrea O. Rossetti
Publication date
01-03-2018
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 3/2018
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-018-0509-5

Other articles of this Issue 3/2018

CNS Drugs 3/2018 Go to the issue

Original Research Article

A Double-Blind, Placebo-Controlled, Phase II Study to Determine the Efficacy, Safety, Tolerability and Pharmacokinetics of a Controlled Release (CR) Formulation of Mazindol in Adults with DSM-5 Attention-Deficit/Hyperactivity Disorder (ADHD)

Review Article

Efficacy and Safety of the Newer Multiple Sclerosis Drugs Approved Since 2010

Review Article

Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents

Review Article

Convergent Mechanisms Underlying Rapid Antidepressant Action

Review Article

Gadolinium-Based Contrast Agent-Related Toxicities

Systematic Review

Adjunctive Eslicarbazepine Acetate in Pediatric Patients with Focal Epilepsy: A Systematic Review and Meta-Analysis