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      Oxcarbazepine for refractory epilepsy: systematic review of the literature Translated title: Oxcarbazepina para epilepsia refratária: revisão sistemática da literatura

      systematic-review

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          ABSTRACT

          CONTEXT AND OBJECTIVE:

          It has been estimated that 50 million people worldwide suffer from epilepsy and around 30% will not achieve adequate control over the disease. The aim was to evaluate the effectiveness of oxcarbazepine for refractory partial or generalized epilepsy.

          METHODS:

          Systematic review. A search was conducted in the PubMed, Lilacs, EMBASE and CENTRAL databases. Studies were analyzed using the Cochrane Collaboration methodology.

          RESULTS:

          Four randomized clinical trials of medium to poor methodological quality were included. Among the adult patients, the chances that they would obtain a 50% reduction in seizure frequency were greater after using oxcarbazepine at doses of 600 mg (relative risk, RR 2.11; 95% confidence interval, CI 1.32 to 3.35), 1,200 mg (RR 3.24; 95% CI 2.11 to 4.98) and 2,400 mg (RR 3.83; 95% CI 2.59 to 5.97). Among the children, the response in the group using oxcarbazepine was also greater (RR 2.11; 95% CI 1.32 to 3.35). The oxcarbazepine doses of 1,200 mg (RR 17.59; 95% CI 2.37 to 130.35) and 2,400 mg (RR 25.41; 95% CI 6.26 to 103.10) were effective for keeping patients probably free from seizures, but the dose of 600 mg was not. There was no significant difference between oxcarbazepine and carbamazepine for controlling the crises.

          CONCLUSIONS:

          There is moderate evidence indicating that oxcarbazepine is effective as an alternative treatment for partial or generalized epilepsy in children and adults who were refractory to previous treatment.

          RESUMO

          CONTEXTO E OBJETIVO:

          Estima-se que 50 milhões de pessoas no mundo sofrem de epilepsia e cerca de 30% não obterão controle adequado da doença. O objetivo foi de avaliar a efetividade de oxcarbazepina na epilepsia parcial ou generalizada refratária.

          MÉTODOS:

          Revisão sistemática. A busca foi nas bases de dados PubMed, Lilacs, EMBASE e CENTRAL. Os estudos foram analisados segundo a metodologia da Cochrane Colaboration.

          RESULTADOS:

          Foram incluídos quatro ensaios clínicos aleatórios de média a má qualidade. Entre os pacientes adultos as chances de obterem redução de 50% na frequência de convulsões foram maiores após uso de oxcarbazepina na dose de 600 mg (risco relativo, RR 2.11; intervalo de confiança, IC 95% 1,32 a 3,35; na dose de 1.200 mg (RR 3,24; IC 95% 2,11 a 4,98) e na dose de 2.400 mg (RR 3,83; IC 95% 2,59 a 5,97). Entre as crianças a resposta no grupo usando oxcarbazepina também foi significativamente maior (RR 2,11; IC 95% 1,32 a 3,35). Oxcarbazepina mostrou probabilidade dos pacientes ficarem livre de convulsões, ser eficaz nas doses de 1.200 mg (RR 17,59; IC 95% 2.37 a 130,35) e 2.400 mg (RR 25,41; IC 95% 6,26 a 103,10) não foi eficaz na dose de 600 mg. Não houve diferença estatística significante entre oxcarbazepina e carbamazepina no controle das crises.

          CONCLUSÕES:

          Há evidências moderada de que a oxcarbazepina é um tratamento eficaz como alternativa para os casos de epilepsia parcial ou generalizada em crianças e adultos que tenham sido refratários a tratamento prévio.

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          Most cited references46

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          Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.

          To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. Meta-analyses from the Cochrane Pregnancy and Childbirth Database. The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.
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            Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE).

            The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) have come to consensus definitions for the terms epileptic seizure and epilepsy. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.
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              • Abstract: found
              • Article: not found

              ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.

              To assess which antiepileptic medications (AEDs) have the best evidence for long-term efficacy or effectiveness as initial monotherapy for patients with newly diagnosed or untreated epilepsy. A 10-member subcommission of the Commission on Therapeutic Strategies of The International League Against Epilepsy (ILAE), including adult and pediatric epileptologists, clinical pharmacologists, clinical trialists, and a statistician evaluated available evidence found through a structured literature review including MEDLINE, Current Contents and the Cochrane Library for all applicable articles from 1940 until July 2005. Articles dealing with different seizure types (for different age groups) and two epilepsy syndromes were assessed for quality of evidence (four classes) based on predefined criteria. Criteria for class I classification were a double-blind randomized controlled trial (RCT) design, >or=48-week treatment duration without forced exit criteria, information on >or=24-week seizure freedom data (efficacy) or >or=48-week retention data (effectiveness), demonstration of superiority or 80% power to detect a
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                Author and article information

                Journal
                Sao Paulo Med J
                Sao Paulo Med J
                Sao Paulo Med J
                São Paulo Medical Journal
                Associação Paulista de Medicina - APM
                1516-3180
                1806-9460
                06 October 2009
                2009
                : 127
                : 3
                : 150-159
                Affiliations
                [1 ] originalMD, PhD. Adjunct professor in the Universidade Federal do Rio Grande do Norte (UFRN), Natal, Rio Grande do Norte, Brazil.
                [2 ] originalMD, PhD. Professor in the Discipline of Emergency Medicine and Evidence-Based Medicine, Department of Medicine, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
                [3 ] originalMHS. Affiliated researcher at Brazilian Cochrane Center and postgraduate student in the Discipline of Emergency Medicine and Evidence-Based Medicine, Department of Medicine, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil.
                [4 ] originalMD, PhD. Full professor of the Discipline of Emergency Medicine and Evidence-Based Medicine, Department of Medicine, Universidade Federal de São Paulo, Escola Paulista de Medicina (Unifesp-EPM), São Paulo, Brazil.
                Author notes
                [Address for correspondence: ] Álvaro Nagib Atallah. Rua Borges Lagoa, 564 - Conj. 61, Edifício Espaço. São Paulo - São Paulo (SP) - Brasil. CEP 04038-000. Tel. (+55 11) 5571-4721. E-mail: atallahmbe@ 123456uol.com.br

                Conflict of interest: None known

                Article
                10.1590/S1516-31802009000300008
                10956889
                19820875
                0866376f-27a5-46f5-bc4d-8c16bebb207d

                This is an open access article distributed under the terms of the Creative Commons license.

                History
                : 28 April 2009
                : 17 July 2009
                : 27 July 2009
                Page count
                Figures: 9, Tables: 2, Equations: 0, References: 27, Pages: 10
                Categories
                Systematic Review

                anticonvulsants,epilepsy,review [publication type],seizures,oxcarbazepine [substance name],anticonvulsivos,epilepsia,revisão [tipo de publicação],convulsões,carbamazepina

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