Analysis of pharmacotherapy regimen and costs in patients with drug-resistant epilepsy following vagus nerve stimulation therapy: a single-center study (Poland)

  • Dorota KopciuchEmail author
  • Anna-Maria Barciszewska
  • Jędrzej Fliciński
  • Tomasz Zaprutko
  • Krzysztof Kus
  • Barbara Steinborn
  • Elżbieta Nowakowska
Original article


Approximately 30–40% of patients with drug-resistant epilepsy (DRE) who underwent vagus nerve stimulator (VNS) implantation achieve above 50% reduction in seizure frequency. VNS proves effective in reducing frequency of seizures in DRE patients, when combined with antiepileptic drugs (AEDs). This raises a question whether improvement of clinical parameters is achieved with VNS only or relies on combined therapy with AEDs. The aim of the study was the analysis of impact of VNS on clinical recovery of patients with DRE and the analysis of pharmacotherapy costs and drug regimen following VNS implantation in DRE patients. The study included all the patients who had VNS implanted at our department in the years 2014–2018. The patients would be followed up for 2 years after the VNS implantation date. The most commonly used drugs included levetiracetam, lacosamide, valproate, oxcarbazepine, and topiramate. Average cost of AEDs in year 1 following VNS implantation was between EUR 15.53 (CLB) and EUR 545.52 (TGB) and in year 2 between EUR 13.51 (NTZ) and EUR 779.44 (LAC). The greatest number of seizures affected the group of patients treated with three drugs. A statistically significant improvement in seizure frequency was observed in the group of patients treated with two and three drugs. With the rising costs of healthcare, the importance of economic efficiency is becoming increasingly relevant. VNS is a reasonable option for saving money in the healthcare system while ensuring measurable clinical and therapeutic outcomes over the long term.


Pharmacotherapy regimen Costs of antiepileptic drugs Drug-resistant epilepsy Vagus nerve stimulation 



The authors would like to acknowledge data analysis support from Anna Paczkowska and Piotr Ratajczak from the Department of Pharmacoeconomics and Social Pharmacy, Poznań University of Medical Sciences, Roman Jankowski from the Department of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, Anna Winczewska-Wiktor from the Department of Developmental Neurology, Poznan University of Medical Sciences.


This study is funded by Poznan University of Medical Sciences (number: 502-14-33164400-09877).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical statement

We acknowledge having read the journal’s position on issues involved in ethical publication and declare that this paper is consistent with those guidelines. The study was approved by the regional ethics committee.

Informed consent

Verbal informed consent was obtained from all individual study subjects.


  1. 1.
    Kwan P, Brodie MJ (2000) Early identification of refractory epilepsy. N Engl J Med 342:314–319. CrossRefPubMedGoogle Scholar
  2. 2.
    Kalilani L, Sun X, Pelgrims B et al (2018) The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis. Epilepsia 59:2179–2193. CrossRefPubMedGoogle Scholar
  3. 3.
    Marson AG, Al-Kharusi AM, Alwaidh M et al (2007) The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 369:1000–1015. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Glauser TA, Cnaan A, Shinnar S et al (2010) Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 362:790–799. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Beleza P (2009) Refractory epilepsy: a clinically oriented review. Eur Neurol 62:65–71. CrossRefPubMedGoogle Scholar
  6. 6.
    Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response—a review. J Neurosurg 115:1248–1255. CrossRefPubMedGoogle Scholar
  7. 7.
    De Herdt V, Boon P, Ceulemans B et al (2007) Vagus nerve stimulation for refractory epilepsy: a Belgian multicenter study. Eur J Paediatr Neurol 11:261–269. CrossRefPubMedGoogle Scholar
  8. 8.
    DeGiorgio CM, Schachter SC, Handforth A et al (2000) Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia 41:1195–1200. CrossRefPubMedGoogle Scholar
  9. 9.
    Elliott RE, Morsi A, Tanweer O et al (2011) Efficacy of vagus nerve stimulation over time: review of 65 consecutive patients with treatment-resistant epilepsy treated with VNS > 10 years. Epilepsy Behav 20:478–483. CrossRefPubMedGoogle Scholar
  10. 10.
    Cramer JA, Menachem EB, French J (2001) Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation. Epilepsy Res 47:17–25. CrossRefPubMedGoogle Scholar
  11. 11.
    Alexopoulos AV, Kotagal P, Loddenkemper T et al (2006) Long-term results with vagus nerve stimulation in children with pharmacoresistant epilepsy. Seizure 15:491–503. CrossRefPubMedGoogle Scholar
  12. 12.
    Elliott RE, Morsi A, Kalhorn SP et al (2011) Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav 20:57–63. CrossRefPubMedGoogle Scholar
  13. 13.
    Panebianco M, Rigby A, Weston J, Marson AG (2015) Vagus nerve stimulation for partial seizures. Cochrane Database Syst Rev. CrossRefPubMedGoogle Scholar
  14. 14.
    Poolos NP, Castagna CE, Williams S et al (2017) Association between antiepileptic drug dose and long-term response in patients with refractory epilepsy. Epilepsy Behav 69:59–68. CrossRefPubMedGoogle Scholar
  15. 15.
    Narodowy Bank Polski—Internetowy Serwis Informacyjny. Accessed 27 Nov 2018
  16. 16.
    Löscher W, Schmidt D (2006) Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia 47:1253–1284. CrossRefPubMedGoogle Scholar
  17. 17.
    Ben-Menachem E, Hellström K, Waldton C, Augustinsson LE (1999) Evaluation of refractory epilepsy treated with vagus nerve stimulation for up to 5 years. Neurology 52:1265–1267CrossRefGoogle Scholar
  18. 18.
    Helmers SL, Wheless JW, Frost M et al (2001) Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol 16:843–848. CrossRefPubMedGoogle Scholar
  19. 19.
    Leppik I (2000) Monotherapy and polypharmacy. Neurology 55(11 Suppl 3):25–29Google Scholar
  20. 20.
    Schmidt D (2016) Drug treatment strategies for epilepsy revisited: starting early or late? One drug or several drugs? Epileptic Disord 18:356–366. CrossRefPubMedGoogle Scholar
  21. 21.
    Révész D, Fröjd V, Rydenhag B, Ben-Menachem E (2018) Estimating long-term vagus nerve stimulation effectiveness: accounting for antiepileptic drug treatment changes. Neuromodul Technol Neural Interface 21:797–804. CrossRefGoogle Scholar
  22. 22.
    Neligan A, Bell GS, Elsayed M et al (2012) Treatment changes in a cohort of people with apparently drug-resistant epilepsy: an extended follow-up. J Neurol Neurosurg Psychiatry 83:810–813. CrossRefPubMedGoogle Scholar
  23. 23.
    de Zélicourt M, de Toffol B, Vespignani H et al (2014) Management of focal epilepsy in adults treated with polytherapy in France: the direct cost of drug resistance (ESPERA study). Seizure 23:349–356. CrossRefPubMedGoogle Scholar
  24. 24.
    Dash D, Aggarwal V, Joshi R et al (2015) Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy. Seizure 27:25–29. CrossRefPubMedGoogle Scholar
  25. 25.
    Luciano AL, Shorvon SD (2007) Results of treatment changes in patients with apparently drug-resistant chronic epilepsy. Ann Neurol 62:375–381. CrossRefPubMedGoogle Scholar
  26. 26.
    van Hout BA, Gagnon DD, McNulty P, O’Hagan A (2003) The cost effectiveness of two new antiepileptic therapies in the absence of direct comparative data. Pharmacoeconomics 21:315–326. CrossRefPubMedGoogle Scholar
  27. 27.
    Beghi E, Atzeni L, Garattini L (2008) Economic analysis of newer antiepileptic drugs. CNS Drugs 22:861–875. CrossRefPubMedGoogle Scholar
  28. 28.
    Fallah A, Weil AG, Wang S et al (2016) Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with tuberous sclerosis complex. Epilepsy Behav 63:79–88. CrossRefPubMedGoogle Scholar

Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  1. 1.Department of Pharmacoeconomics and Social PharmacyPoznań University of Medical SciencesPoznanPoland
  2. 2.Department of Neurosurgery and NeurotraumatologyPoznań University of Medical SciencesPoznanPoland
  3. 3.Department of Neurosurgery and NeurotraumatologyHeliodor Swiecicki Clinical HospitalPoznanPoland
  4. 4.Department of Developmental NeurologyPoznań University of Medical SciencesPoznanPoland

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