Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2021; 79(04): 290-298
DOI: 10.1590/0004-282X-ANP-2020-0082
ARTICLE

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

Eficácia e segurança do levetiracetam como terapia adjunta na epilepsia focal refratária
Maria Luiza Giraldes de MANREZA 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Centro de Pesquisa, São Paulo SP, Brazil.
,
Tatiane Amaral PAN 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Eduardo Quinalha CARBONE 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Antonio Carlos Amedeo VATTIMO 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Renata HERRERA 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Douglas Costa MORAIS 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Rita Antonelli CARDOSO 
3   STATS Estatística em Ciências e Negócios, São Paulo SP, Brazil.
,
Glenda Corrêa Borges de LACERDA 
4   Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Rio de Janeiro RJ, Brazil.
,
Katia LIN 
5   Universidade Federal de Santa Catarina, Hospital Universitário, Núcleo de Pesquisa em Neurologia Experimental e Clínica, Florianópolis SC, Brazil.
,
Frederico Nakane NAKANO 
6   Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Hospital das Clínicas, Unidade de Pesquisa Clínica, Ribeirão Preto SP, Brazil.
,
Pedro André KOWACS 
7   Instituto de Neurologia de Curitiba, Curitiba PR, Brazil.
,
André Luis Fernandes PALMINI 
8   Pontifícia Universidade Católica do Rio Grande do Sul, Hospital São Lucas, Centro de Pesquisa Clínica, Porto Alegre RS, Brazil.
,
Adélia Maria de Miranda Henriques SOUZA 
9   Instituto de Medicina Integral Prof. Fernando Figueira, Recife PE, Brazil.
,
Stevin ZUNG 
2   Aché Laboratórios Farmacêuticos S.A., Núcleo de Inovação, Núcleo Médico-Científico, Guarulhos SP, Brazil.
,
Elza Márcia Targas YACUBIAN 
10   Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Neurologia e Neurocirurgia, São Paulo SP, Brazil.
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

RESUMO

Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.

Keywords:

Levetiracetam - Refractory Epilepsy - Focal Seizures - Antiseizure Medications - Seizures

Palavras-chave:

Levetiracetam - Epilepsia Refratária - Crises Focais - Fármacos Anticrise - Crises Epilépticas

Authors’ contributions:

All authors participated in the preparation and review of the article and were responsible for the submission.




Publication History

Received: 04 March 2020

Accepted: 10 August 2020

Article published online:
01 June 2023

© 2021. Academia Brasileira de Neurologia. 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 commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Lyseng-Williamson KA. Spotlight on levetiracetam in epilepsy. CNS Drugs. 2011 Oct;25(10):901-5. https://doi.org/10.2165/11208340-20200082000-00000
  • 2 World Health Organization. Epilepsy: Key facts. 2018. Available in: http://www.who.int/news-room/fact-sheets/detail/epilepsy.
  • 3 Mbizvo GK, Dixon P, Hutton JL, Marson AG. The adverse effects profile of levetiracetam in epilepsy: a more detailed look. Int J Neurosci. 2014 Sep;124(9):627-34. https://doi.org/10.3109/00207454.2013.866951
  • 4 Engel J Jr. Approaches to refractory epilepsy. Ann Indian Acad Neurol. 2014 Mar;17(Suppl 1):S12-7. https://doi.org/10.4103/0972-2327.128644.
  • 5 Mbizvo GK, Dixon P, Hutton JL, Marson AG. Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane Review. Cochrane Database Syst Rev. 2012 Sep;2012(9):CD001901. https://doi.org/10.1002/14651858.CD001901.pub2
  • 6 Huber B, Bömmel W, Hauser I, Horstmann V, Liem S, May T, et al. Efficacy and tolerability of levetiracetam in patients with therapy-resistant epilepsy and learning disabilities. Seizure. 2004 Apr;13(3):168-75. https://doi.org/10.1016/S1059-1311(03)00154-7
  • 7 Chen D, Bian H, Zhang L. A meta-analysis of levetiracetam for randomized placebo-controlled trials in patients with refractory epilepsy. Neuropsychiatr Dis Treat. 2019 Apr;15:905-917. https://doi.org/10.2147/NDT.S188111
  • 8 Fischer RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):522-30. https://doi.org/10.1111/epi.13670
  • 9 da Silva TI, Ciconelli RM, Alonso NB, Azevedo AM, Westphal-Guitti AC, Pascalicchio TF, et al. Validity and reliability of the Portuguese version of the quality of life in epilepsy inventory (QOLIE-31) for Brazil. Epilepsy Behav. 2007 Mar;10(2):234-41. https://doi.org/10.1016/j.yebeh.2006.08.022
  • 10 Barbosa FD. Versão brasileira do inventario de qualidade de vida para adolescentes com epilepsia "QOLIE - AD - 48" [thesis]. Campinas: Universidade Estadual de Campinas, Faculdade de Ciências Médicas; 2007. Available from: http://www.repositorio.unicamp.br/handle/REPOSIP/309061
  • 11 de Oliveira GN, Kummer A, Salgado JV, Portela EJ, Sousa-Pereira SR, David AS, et al. Brazilian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). Epilepsy Behav. 2010 Nov;19(3):328-31. https://doi.org/10.1016/j.yebeh.2010.07.013
  • 12 Cao Y, He X, Zhao L, He Y, Wang S, Zhang T, et al. Efficacy and safety of Levetiracetam as adjunctive treatment in children with focal onset seizures: A systematic review and meta-analysis. Epilepsy Res. 2019 Jul;153:40-8. https://doi.org/10.1016/j.eplepsyres.2019.04.001
  • 13 López-Góngora M, Martínez-Domeño A, García C, Escartín A. Effect of levetiracetam on cognitive functions and quality of life: a one-year follow-up study. Epileptic Disord. 2008 Dec;10(4):297-305. https://doi.org/10.1684/epd.2008.0227.
  • 14 Shorvon SD, Löwenthal A, Janz D, Bielen E, Loiseau P. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. Epilepsia. 2000 Sep;41(9):1179-86. https://doi.org/10.1111/j.1528-1157.2000.tb00323.x.
  • 15 Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000 Jul;55(2):236-42. https://doi.org/10.1212/wnl.55.2.236
  • 16 Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. Epilepsia. 2000 Oct;41(10):1276-83. https://doi.org/10.1111/j.1528-1157.2000.tb04605.x