Comparison efficacy and safety sodium valproate versus combination sodium valproate and levetiracetam for treatment epilepsy in children: a meta-analysis
Main Article Content
Keywords
levetiracetam (LEV), sodium valproate (SV), epilepsy, efficacy, safety, children
Abstract
Background: The most prevalent severe neurological condition, impacting more than 50 million individuals globally, is epilepsy. A new anti-epileptic drug (AED) called levetiracetam (LEV) has shown promise as an adjuvant treatment for children's treatment-resistant partial-onset seizures. Sodium valproate (SV) is a commonly used anti-epileptic medication that has a range of effects and a distinct mode of action. Combining LEV and SV has emerged as a viable clinical treatment plan. This study aimed to use meta-analysis to estimate the safety and effectiveness of LEV with SV in pediatric epilepsy patients.
Methods: From January 1993 to April 2023, the Cochrane Library, PubMed, and ScienceDirect were searched. The included literature consisted of randomized controlled clinical trials that examined the use of SV in conjunction with LEV in pediatric epileptic patients. This meta-analysis followed the PRISMA guidelines. The statistical program used for the meta-analysis was Revman V.5.4.1.
Results: From 568 original titles screened, data were extracted from 3 studies (n=303). Compared with SV alone, SV combined with LEV significantly improved the overall therapeutic effect of epilepsy (OR=0.80; 95%CI= 0.72-0.89; p<0.0001). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) of nausea and vomiting (OR=2.77; 95%CI=1.08-7.09; p=0.03).
Conclusion: According to this meta-analysis, SV plus LEV considerably increased the overall therapeutic effect of epilepsy while concurrently lowering the incidence of ADRs when compared to SV alone. Thus, for treating epilepsy in children, we advise SV in conjunction with LEV.
References
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29. Suryani G, Jehosua SY, Herlyani K, Zhi-Jien C, Kheng-Seang L. Attitudes toward epilepsy in Indonesia. Epilepsy & Behavior. 2021;123:108244.
30. Endriastuti NE, Suryoputri MW, Ilma DL. THE EVALUATION OF ANTI-EPILEPTIC DRUGS DOSAGE IN MALNOURISHED CHILDREN: CASES IN INDONESIAN COMMUNITY OF EPILEPSY. Jurnal Farmasi Sains dan Praktis. 2022;142–50.
31. Kanner AM, Bicchi MM. Anti-seizure Medications for Adults With Epilepsy: A Review. JAMA. 2022;327(13):1269–81. Available from: https://doi.org/10.1001/jama.2022.3880
32. Sekarsari D, Kalanjati VP, Machin A, Gunawan PI. PROFILE OF EPILEPSY PATIENTS IN PEDIATRIC WARD AT DR. SOETOMO GENERAL ACADEMIC HOSPITAL, SURABAYA, INDONESIA IN THE PERIOD OF JANUARY-DECEMBER 2017. Majalah Biomorfologi. 2020;30(2):34.
33. Zaccara G, Lattanzi S, Brigo F. Which treatment strategy in patients with epilepsy with focal seizures uncontrolled by the first anti-seizure medication? Vol. 121, Epilepsy and Behavior. Academic Press Inc.; 2021.
34. Szychot E, Walker D, Collins P, Hyare H, Shankar A, Bienemann A, et al. Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. Int J Clin Oncol. 2021;26(4):647–58.
35. Mei X, Wu HC, Ruan M, Cai LR. Acute Liver Failure with Thrombotic Microangiopathy Due to Sodium Valproate Toxicity: A Case Report. World J Clin Cases. 2021;9(17):4310–7.
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40. Kandilli B, Ugur Kaplan AB, Cetin M, Taspinar N, Ertugrul MS, Aydin IC, et al. Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies. Drug Dev Ind Pharm. 2020;46(7):1063–72.
41. Oliva CF, Gangi G, Marino S, Marino L, Messina G, Sciuto S, et al. Single and in combination antiepileptic drug therapy in children with epilepsy: how to use it. AIMS Med Sci. 2021;8(2):138–46. Available from: http://www.aimspress.com/article/doi/10.3934/medsci.2021013
42. Kaminski RM, Matagne A, Patsalos PN, Klitgaard H. Benefit of combination therapy in epilepsy: A review of the preclinical evidence with levetiracetam. Epilepsia. 2009;50(3):387–97.
43. Suryoputri MW, Endriastuti NE, Ilma DL. Effects of Antiepileptic Drug Levels on Clinical Outcomes in Pediatric Patients Using Pharmacokinetics Approach. Indonesian Journal of Clinical Pharmacy. 2021;10(4):272–88.
44. Gong L, Yang W, Deng Y, Wang T, Li W, Ye Y, et al. Original Article Clinical efficacy and safety of the combined use of sodium valproate and levetiracetam in epilepsy children [Internet]. Vol. 13, Int J Clin Exp Med. 2020. Available from: www.ijcem.com/
2. Packer RMA, Volk HA. Epilepsy beyond seizures: A review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs. Vol. 177, Veterinary Record. British Veterinary Association; 2015. p. 306–15.
3. Falco-Walter J. Epilepsy-Definition, Classification, Pathophysiology, and Epidemiology. Semin Neurol. 2020;40(6):617–23.
4. Minardi C, Minacapelli R, Valastro P, Vasile F, Pitino S, Pavone P, et al. Epilepsy in children: From diagnosis to treatment with focus on emergency. Vol. 8, Journal of Clinical Medicine. MDPI; 2019.
5. Zhu Y, Yang J, Zhu X. Combined effects of levetiracetam and sodium valproate on paediatric patients with epilepsy: a systematic review and meta-analysis. Vol. 95, Seizure. W.B. Saunders Ltd; 2022. p. 17–25.
6. Rakhade SN, Jensen FE. Epileptogenesis in the immature brain: Emerging mechanisms. Vol. 5, Nature Reviews Neurology. 2009. p. 380–91.
7. Dwivedi R, Ramanujam B, Chandra PS, Sapra S, Gulati S, Kalaivani M, et al. Surgery for Drug-Resistant Epilepsy in Children. New England Journal of Medicine. 2017;377(17):1639–47.
8. Penovich P, Glauser T, Becker D, Patel AD, Sirven J, Long L, et al. Recommendations for development of acute seizure action plans (ASAPs) from an expert panel. Vol. 123, Epilepsy and Behavior. Academic Press Inc.; 2021.
9. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS. Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII). Vol. 58, Epilepsia. Blackwell Publishing Inc.; 2017. p. 181–221.
10. Dhrivastava AK, Shrivastav A, Shrivastav M, Gupta A, Prakash S, Fatima A, et al. Epilepsy: the next generation drugs (a review). Journal of Drug Delivery and Therapeutics. 2019;9(1):286–92.
11. Potschka H, Trinka E. Perampanel: Does it have broad-spectrum potential? Vol. 60, Epilepsia. Blackwell Publishing Inc.; 2019. p. 22–36.
12. Vorderwülbecke BJ, Wandschneider B, Weber Y, Holtkamp M. Genetic generalized epilepsies in adults — challenging assumptions and dogmas. Nat Rev Neurol. 2022;18(2):71–83. Available from: https://doi.org/10.1038/s41582-021-00583-9
13. Delage C, Palayer M, Etain B, Hagenimana M, Blaise N, Smati J, et al. Valproate, divalproex, valpromide: Are the differences in indications justified? Vol. 158, Biomedicine and Pharmacotherapy. Elsevier Masson s.r.l.; 2023.
14. Elvir-Lazo OL, White PF, Cruz Eng H, Yumul F, Chua R, Yumul R. Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I). Postgrad Med. 2021;133(8):939–52. Available from: https://doi.org/10.1080/00325481.2021.1982297
15. Akyüz E, Köklü B, Ozenen C, Arulsamy A, Shaikh MohdF. Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy. Curr Neuropharmacol. 2021;19(11):1865–83.
16. Celdran de Castro A, Nascimento FA, Beltran-Corbellini Á, Toledano R, Garcia-Morales I, Gil-Nagel A, et al. Levetiracetam, from broad-spectrum use to precision prescription: A narrative review and expert opinion. Seizure. 2023;107:121–31.
17. Katzung BG. Basic & clinical pharmacology. 14th ed. Katzung BG, editor. 2015. 422–427 p.
18. Kliegman R. Nelson Textbook of Pediatrics, 2-Volume Set, Twentieth Edition (2016). 2016.
19. Singh G, Rees JH, Sander JW. Seizures and epilepsy in oncological practice: Causes, course, mechanisms and treatment. Vol. 78, Journal of Neurology, Neurosurgery and Psychiatry. BMJ Publishing Group; 2007. p. 342–9.
20. Mbizvo GK, Dixon P, Hutton JL, Marson AG. The adverse effects profile of levetiracetam in epilepsy: A more detailed look. Vol. 124, International Journal of Neuroscience. Informa Healthcare; 2014. p. 627–34.
21. Marson A, Burnside G, Appleton R, Smith D, Leach JP, Sills G, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial [Internet]. Vol. 397, www.thelancet.com. 2021. Available from: www.thelancet.com
22. Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Systematic Reviews. 2022;18(2).
23. Luchini C, Veronese N, Nottegar A, Shin J Il, Gentile G, Granziol U, et al. Assessing the quality of studies in meta-research: Review/guidelines on the most important quality assessment tools. Vol. 20, Pharmaceutical Statistics. John Wiley and Sons Ltd; 2021. p. 185–95.
24. Liu Z, Li J, Yang F, Hu Y, Liu J, Hu H, et al. Sodium valproate combined with levetiracetam in pediatric epilepsy and its influence on NSE, IL 6, hs CRP and electroencephalogram improvement. Exp Ther Med. 2020;
25. Chen M, Jiang Y, Ma L, Zhou X, Wang N. Comparison of the Therapeutic Effects of Sodium Valproate and Levetiracetam on Pediatric Epilepsy and the Effects of Nerve Growth Factor and γ-Aminobutyric Acid [Internet]. Vol. 50, Iran J Public Health. 2021. Available from: https://creativecommons.org/licenses/by-nc/4.0/
26. Zhao J, Sang Y, Zhang Y, Zhang D, Chen J, Liu X. Efficacy of levetiracetam combined with sodium valproate on pediatric epilepsy and its effect on serum miR-106b in children. Exp Ther Med. 2019;
27. Molla A, Mekuriaw B, Habtamu E, Mareg M. Knowledge and attitude towards epilepsy among rural residents in southern Ethiopia: a cross-sectional study. BMC Public Health. 2021;21(1).
28. Harjaningsih W, Rahmania E, Firdha SN. Adverse drug reaction of antiepileptic monotherapy on epileptic paediatric patients in Dr Sardjito Hospital, Yogyakarta, Indonesia. Pharmacy Education. 2022;22(2):242–7.
29. Suryani G, Jehosua SY, Herlyani K, Zhi-Jien C, Kheng-Seang L. Attitudes toward epilepsy in Indonesia. Epilepsy & Behavior. 2021;123:108244.
30. Endriastuti NE, Suryoputri MW, Ilma DL. THE EVALUATION OF ANTI-EPILEPTIC DRUGS DOSAGE IN MALNOURISHED CHILDREN: CASES IN INDONESIAN COMMUNITY OF EPILEPSY. Jurnal Farmasi Sains dan Praktis. 2022;142–50.
31. Kanner AM, Bicchi MM. Anti-seizure Medications for Adults With Epilepsy: A Review. JAMA. 2022;327(13):1269–81. Available from: https://doi.org/10.1001/jama.2022.3880
32. Sekarsari D, Kalanjati VP, Machin A, Gunawan PI. PROFILE OF EPILEPSY PATIENTS IN PEDIATRIC WARD AT DR. SOETOMO GENERAL ACADEMIC HOSPITAL, SURABAYA, INDONESIA IN THE PERIOD OF JANUARY-DECEMBER 2017. Majalah Biomorfologi. 2020;30(2):34.
33. Zaccara G, Lattanzi S, Brigo F. Which treatment strategy in patients with epilepsy with focal seizures uncontrolled by the first anti-seizure medication? Vol. 121, Epilepsy and Behavior. Academic Press Inc.; 2021.
34. Szychot E, Walker D, Collins P, Hyare H, Shankar A, Bienemann A, et al. Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy. Int J Clin Oncol. 2021;26(4):647–58.
35. Mei X, Wu HC, Ruan M, Cai LR. Acute Liver Failure with Thrombotic Microangiopathy Due to Sodium Valproate Toxicity: A Case Report. World J Clin Cases. 2021;9(17):4310–7.
36. Strzelczyk A, Schubert-Bast S. A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication. CNS Drugs. 2022;36(3):217–37.
37. Hakami T. Neuropharmacology of Anti-seizure Drugs. Vol. 41, Neuropsychopharmacology Reports. John Wiley and Sons Inc; 2021. p. 336–51.
38. Li KY, Hsu CY, Yang YH. A review of cognitive and behavioral outcomes of Brivaracetam. Vol. 39, Kaohsiung Journal of Medical Sciences. John Wiley and Sons Inc; 2023. p. 104–14.
39. Löscher W, Klein P. The Pharmacology and Clinical Efficacy of Anti-seizure Medications: From Bromide Salts to Cenobamate and Beyond. Vol. 35, CNS Drugs. Adis; 2021. p. 935–63.
40. Kandilli B, Ugur Kaplan AB, Cetin M, Taspinar N, Ertugrul MS, Aydin IC, et al. Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies. Drug Dev Ind Pharm. 2020;46(7):1063–72.
41. Oliva CF, Gangi G, Marino S, Marino L, Messina G, Sciuto S, et al. Single and in combination antiepileptic drug therapy in children with epilepsy: how to use it. AIMS Med Sci. 2021;8(2):138–46. Available from: http://www.aimspress.com/article/doi/10.3934/medsci.2021013
42. Kaminski RM, Matagne A, Patsalos PN, Klitgaard H. Benefit of combination therapy in epilepsy: A review of the preclinical evidence with levetiracetam. Epilepsia. 2009;50(3):387–97.
43. Suryoputri MW, Endriastuti NE, Ilma DL. Effects of Antiepileptic Drug Levels on Clinical Outcomes in Pediatric Patients Using Pharmacokinetics Approach. Indonesian Journal of Clinical Pharmacy. 2021;10(4):272–88.
44. Gong L, Yang W, Deng Y, Wang T, Li W, Ye Y, et al. Original Article Clinical efficacy and safety of the combined use of sodium valproate and levetiracetam in epilepsy children [Internet]. Vol. 13, Int J Clin Exp Med. 2020. Available from: www.ijcem.com/