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Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta-analyses

2016; Wiley; Volume: 36; Issue: 12 Linguagem: Inglês

10.1002/phar.1855

1875-9114

Marília Silveira de Almeida Campos, Lorena Rocha Ayres, Manuela Roque Siane Morelo, Fabiana Angelo Marques, Leonardo Régis Leira Pereira,

Drug Transport and Resistance Mechanisms

Pharmacotherapy: The Journal of Human Pharmacology and Drug TherapyVolume 36, Issue 12 p. 1255-1271 Review of Therapeutics Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta-analyses Marília Silveira de Almeida Campos, Corresponding Author Marília Silveira de Almeida Campos mariliac@fcfrp.usp.br School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilAddress for correspondence: Marília Silveira de Almeida Campos, Avenida do Café, s/n°. Ribeirão Preto, São Paulo, Brazil; e-mail: mariliac@fcfrp.usp.br.Search for more papers by this authorLorena Rocha Ayres, Lorena Rocha Ayres Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, BrazilSearch for more papers by this authorManuela Roque Siane Morelo, Manuela Roque Siane Morelo School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorFabiana Angelo Marques, Fabiana Angelo Marques School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorLeonardo Régis Leira Pereira, Leonardo Régis Leira Pereira School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this author Marília Silveira de Almeida Campos, Corresponding Author Marília Silveira de Almeida Campos mariliac@fcfrp.usp.br School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilAddress for correspondence: Marília Silveira de Almeida Campos, Avenida do Café, s/n°. Ribeirão Preto, São Paulo, Brazil; e-mail: mariliac@fcfrp.usp.br.Search for more papers by this authorLorena Rocha Ayres, Lorena Rocha Ayres Department of Pharmaceutical Sciences, Federal University of Espírito Santo, Vitória, BrazilSearch for more papers by this authorManuela Roque Siane Morelo, Manuela Roque Siane Morelo School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorFabiana Angelo Marques, Fabiana Angelo Marques School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this authorLeonardo Régis Leira Pereira, Leonardo Régis Leira Pereira School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, BrazilSearch for more papers by this author First published: 25 October 2016 https://doi.org/10.1002/phar.1855Citations: 27Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta-analyses using a Bayesian random-effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs—levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate—should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults. Citing Literature Supporting Information Filename Description phar1855-sup-0001-AppendixS1-S3.docxWord document, 89.9 KB Appendix S1. Eletronic search strategy in each database. Appendix S2. Network meta-analyses of the antiepileptic drugs with all included studies. Appendis S3. Network meta-analyses of the antiepileptic drugs performed in the sensitivity analysis. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume36, Issue12December 2016Pages 1255-1271 RelatedInformation