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CC BY-NC-ND 4.0 · Asian J Neurosurg 2024; 19(04): 728-734
DOI: 10.1055/s-0044-1790516
Original Article

Comparison of Effectiveness of Brivaracetam and Levetiracetam for Prophylaxis of Early Post-Traumatic Seizures: A Prospective Comparative Interventional Study

Rajan Pandya
1   Department of Neurosurgery, Goa Medical College, Panaji, Goa, India
,
Ponraj Kamatchi Sundaram
1   Department of Neurosurgery, Goa Medical College, Panaji, Goa, India
,
Shashank Singh Baghel 
1   Department of Neurosurgery, Goa Medical College, Panaji, Goa, India
› Author Affiliations Funding None.
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Abstract

Introduction Early posttraumatic seizures (EPTS) are a major complication after a head injury, defined as seizures developing within the first 7 days of trauma. Levetiracetam has become a popular drug for the prevention of posttraumatic seizures in institutions worldwide. However, it has been reportedly associated with adverse effects like behavioral changes and somnolence. This study aimed to compare the efficacy of a newer drug, brivaracetam, which is reported to have a better pharmacokinetic profile. These findings may be significant in providing a safer yet efficacious alternative to levetiracetam.

Objective The aim of this study was to evaluate the efficacy of brivaracetam for prophylaxis of EPTS and to compare it with levetiracetam.

Materials and Methods A prospective, single-blind, parallel-group (alternate allocation) controlled trial over 100 patients admitted with traumatic brain injury in the Department of Neurosurgery, Goa Medical College, Panaji, Goa, India. The data was analyzed using IBM SPSS Statistics 29.0.

Results Twenty patients developed EPTS in the study group: 8 from the group receiving brivaracetam and 12 from the group receiving levetiracetam. Although the brivaracetam group had a lower incidence of EPTS, the difference was not statistically significant. Eleven patients from the levetiracetam group developed side effects, while six patients from the brivaracetam group had side effects. There was no significant difference in the incidence of side effects.

Conclusion Brivaracetam has efficacy equal to that of levetiracetam for prophylaxis of EPTS.

Keywords

early posttraumatic seizure - traumatic brain injury - seizure prophylaxis - brivaracetam - levetiracetam

Note

Clinical Trial Registry – India (ICMR-NIMS) Reg. no. CTRI/2023/11/073013. Registered with Clinical Trial Registry-India (ICMR-NIMS) CTRI/2023/11/059371.


Ethical Approval

Ethical clearance obtained from Goa Medical College Institutional ethics committee with reference number GMCIEC/2023/07.




Publication History

Article published online:
10 September 2024

© 2024. Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Ghajar J. Traumatic brain injury. Lancet 2000; 356 (9233) 923-929
    CrossrefPubMedSearch in Google Scholar
  • 2 Pathak SM, Ziechmann R, Menzer J, Hoeft A, Villanueva P. Discontinuation of levetiracetam and valproic acid due to adverse effects in early post-traumatic seizure prophylaxis. Cureus 2023; 15 (10) e47742
    PubMedSearch in Google Scholar
  • 3 Yablon SA. Posttraumatic seizures. Arch Phys Med Rehabil 1993; 74 (09) 983-1001
    PubMedSearch in Google Scholar
  • 4 Majidi S, Makke Y, Ewida A, Sianati B, Qureshi AI, Koubeissi MZ. Prevalence and risk factors for early seizure in patients with traumatic brain injury: analysis from National Trauma Data Bank. Neurocrit Care 2017; 27 (01) 90-95
    CrossrefPubMedSearch in Google Scholar
  • 5 Fordington S, Manford M. A review of seizures and epilepsy following traumatic brain injury. J Neurol 2020; 267 (10) 3105-3111
    CrossrefPubMedSearch in Google Scholar
  • 6 Lamar CD, Hurley RA, Rowland JA, Taber KH. Post-traumatic epilepsy: review of risks, pathophysiology, and potential biomarkers. J Neuropsychiatry Clin Neurosci 2014; 26 (02) iv-113
    CrossrefPubMedSearch in Google Scholar
  • 7 Torbic H, Forni AA, Anger KE, Degrado JR, Greenwood BC. Use of antiepileptics for seizure prophylaxis after traumatic brain injury. Am J Health Syst Pharm 2013; 70 (09) 759-766
    CrossrefPubMedSearch in Google Scholar
  • 8 Sharma S, Tiarks G, Haight J, Bassuk AG. Neuropathophysiological mechanisms and treatment strategies for post-traumatic epilepsy. Front Mol Neurosci 2021; 14: 612073
    CrossrefPubMedSearch in Google Scholar
  • 9 Wohns RN, Wyler AR. Prophylactic phenytoin in severe head injuries. J Neurosurg 1979; 51 (04) 507-509
    CrossrefPubMedSearch in Google Scholar
  • 10 Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 1990; 323 (08) 497-502
    CrossrefPubMedSearch in Google Scholar
  • 11 Englander J, Cifu DX, Diaz-Arrastia R, Center MSKT. Seizures after traumatic brain injury. Arch Phys Med Rehabil 2014; 95 (06) 1223
    CrossrefPubMedSearch in Google Scholar
  • 12 Xu JC, Shen J, Shao WZ. et al. The safety and efficacy of levetiracetam versus phenytoin for seizure prophylaxis after traumatic brain injury: a systematic review and meta-analysis. Brain Inj 2016; 30 (09) 1054-1061
    CrossrefPubMedSearch in Google Scholar
  • 13 Bakr A, Belli A. A systematic review of levetiracetam versus phenytoin in the prevention of late post-traumatic seizures and survey of UK neurosurgical prescribing practice of antiepileptic medication in acute traumatic brain injury. Br J Neurosurg 2018; 32 (03) 237-244
    CrossrefPubMedSearch in Google Scholar
  • 14 Harden C. Safety profile of levetiracetam. Epilepsia 2001; 42 (Suppl. 04) 36-39
    CrossrefPubMedSearch in Google Scholar
  • 15 Wilcock A, Charlesworth S, Toller CS, Girish R, Mihalyo M, Howard P. Therapeutic reviews. J Pain Symptom Manage 2018; 56 (02) 295-301
    PubMedSearch in Google Scholar
  • 16 Klitgaard H, Matagne A, Nicolas JM. et al. Brivaracetam: rationale for discovery and preclinical profile of a selective SV2A ligand for epilepsy treatment. Epilepsia 2016; 57 (04) 538-548
    CrossrefPubMedSearch in Google Scholar
  • 17 Yates SL, Fakhoury T, Liang W, Eckhardt K, Borghs S, D'Souza J. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav 2015; 52 (Pt A): 165-168
    CrossrefPubMedSearch in Google Scholar
  • 18 Galvagno Jr SM, Nahmias JT, Young DA. Advanced trauma life support® Update 2019: management and applications for adults and special populations. Anesthesiol Clin 2019; 37 (01) 13-32
    CrossrefPubMedSearch in Google Scholar
  • 19 Davis T, Ings A. Head injury: triage, assessment, investigation and early management of head injury in children, young people and adults (NICE guideline CG 176). Arch Dis Child Educ Pract 2015; 100 (02) 97-100
    CrossrefPubMedSearch in Google Scholar
  • 20 Carney N, Totten AM, O'Reilly C. et al. Guidelines for the management of severe traumatic brain injury. Neurosurgery 2017; 80 (01) 6-15
    CrossrefPubMedSearch in Google Scholar
  • 21 Pieracci FM, Moore EE, Beauchamp K. et al. A cost-minimization analysis of phenytoin versus levetiracetam for early seizure pharmacoprophylaxis after traumatic brain injury. J Trauma Acute Care Surg 2012; 72 (01) 276-281
    CrossrefPubMedSearch in Google Scholar
  • 22 Löscher W, Hönack D. Profile of ucb L059, a novel anticonvulsant drug, in models of partial and generalized epilepsy in mice and rats. Eur J Pharmacol 1993; 232 (2-3): 147-158
    CrossrefPubMedSearch in Google Scholar
  • 23 Milovanović JR, Janković SM, Pejčić A. et al. Evaluation of brivaracetam: a new drug to treat epilepsy. Expert Opin Pharmacother 2017; 18 (13) 1381-1389
    CrossrefPubMedSearch in Google Scholar
  • 24 Genton P, Van Vleymen B. Piracetam and levetiracetam: close structural similarities but different pharmacological and clinical profiles. Epileptic Disord 2000; 2 (02) 99-105
    CrossrefPubMedSearch in Google Scholar
  • 25 Winblad B. Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Rev 2005; 11 (02) 169-182
    CrossrefPubMedSearch in Google Scholar
  • 26 Klitgaard H, Verdru P. Levetiracetam: the first SV2A ligand for the treatment of epilepsy. Expert Opin Drug Discov 2007; 2 (11) 1537-1545
    CrossrefPubMedSearch in Google Scholar
  • 27 Genton P, Gélisse P. Antimyoclonic effect of levetiracetam. Epileptic Disord 2000; 2 (04) 209-212
    CrossrefPubMedSearch in Google Scholar
  • 28 Lynch BA, Lambeng N, Nocka K. et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. In: Proceedings of the National Academy of Sciences,. 101; 2004
  • 29 Noyer M, Gillard M, Matagne A, Hénichart JP, Wülfert E. The novel antiepileptic drug levetiracetam (ucb L059) appears to act via a specific binding site in CNS membranes. Eur J Pharmacol 1995; 286 (02) 137-146
    CrossrefPubMedSearch in Google Scholar
  • 30 Niespodziany I, Klitgaard H, Margineanu DG. Levetiracetam inhibits the high-voltage-activated Ca(2+) current in pyramidal neurones of rat hippocampal slices. Neurosci Lett 2001; 306 (1-2): 5-8
    CrossrefPubMedSearch in Google Scholar
  • 31 Kaminski RM, Gillard M, Leclercq K. et al. Proepileptic phenotype of SV2A-deficient mice is associated with reduced anticonvulsant efficacy of levetiracetam. Epilepsia 2009; 50 (07) 1729-1740
    CrossrefPubMedSearch in Google Scholar
  • 32 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
    CrossrefPubMedSearch in Google Scholar
  • 33 Englander J, Bushnik T, Duong TT. et al. Analyzing risk factors for late posttraumatic seizures: a prospective, multicenter investigation. Arch Phys Med Rehabil 2003; 84 (03) 365-373
    CrossrefPubMedSearch in Google Scholar
  • 34 Centers for Disease Control and Prevention. Traumatic Brain Injury in the United States: Emergency Department Visits, Hospital- izations, and Deaths, 2002–2006. Atlanta, GA: Centers for Disease Control and Prevention; 2012
    Search in Google Scholar
  • 35 Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia 2003; 44 (s10): 18-20
    CrossrefPubMedSearch in Google Scholar
  • 36 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 (01) 57-78
    CrossrefPubMedSearch in Google Scholar
  • 37 Mula M, Trimble MR, Sander JW. Psychiatric adverse events in patients with epilepsy and learning disabilities taking levetiracetam. Seizure 2004; 13 (01) 55-57
    CrossrefPubMedSearch in Google Scholar
  • 38 Ryvlin P, Werhahn KJ, Blaszczyk B, Johnson ME, Lu S. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia 2014; 55 (01) 47-56
    CrossrefPubMedSearch in Google Scholar
  • 39 Brandt C, Klein P, Badalamenti V, Gasalla T, Whitesides J. Safety and tolerability of adjunctive brivaracetam in epilepsy: in-depth pooled analysis. Epilepsy Behav 2020; 103 (Pt A): 106864
    CrossrefPubMedSearch in Google Scholar