Muller M, Marson A G, Williamson P R
Institute for Maritime Technology, P O Box 181, Simon's Town, 7995, South Africa.
Cochrane Database Syst Rev. 2006 Apr 19(2):CD003615. doi: 10.1002/14651858.CD003615.pub2.
Worldwide, phenytoin is a commonly used antiepileptic drug. Oxcarbazepine is one of the newer antiepileptic drugs and has similar chemical properties to its parent compound carbamazepine. For the new drugs such as oxcarbazepine, it is important to know how they compare with standard treatments.
To review the best evidence comparing oxcarbazepine and phenytoin when used as monotherapy in patients with epilepsy.
We searched the Cochrane Epilepsy Group's Specialized Register (December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), and MEDLINE (1966 to November 2005). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted pharmaceutical companies to try and identify any unpublished studies.
Randomized controlled trials in children or adults with epilepsy. Trials must have included a comparison of oxcarbazepine monotherapy with phenytoin monotherapy.
This was an individual patient data review. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Outcomes were (a) time on allocated treatment; (b) time to achieve 6, 12 and 24-month remission; (c) time to first seizure post randomization; (d) quality of life measures if available. Clinical heterogeneity was assessed by reviewing differences across trials in characteristics of randomized patients, dosing protocols and trial design. Data were analysed on an intention to treat basis. Stratified logrank tests were used to obtain study-specific and overall estimates of hazard ratios (with 95% confidence intervals), where a HR > 1 indicates that an event is more likely on phenytoin.
Individual patient data were available for 480 patients from two trials, representing 100% of the patients recruited into the two trials that met our inclusion criteria. By convention, for the outcomes time to withdrawal of allocated treatment and time to first seizure a hazards ratio (HR) > 1 indicates a clinical advantage for oxcarbazepine and for time to 6 and 12-month remission a HR > 1 indicates a clinical advantage for phenytoin. The main overall results (HR, 95% confidence interval (CI)) were: (i) time to withdrawal of allocated treatment 1.64 (1.09 to 2.47), (ii) time to 6-month remission 0.89 (0.66 to 1.22), (iii) time to 12-month remission 0.92 (0.62 to 1.37), (iv) time to first seizure 1.07 (0.83 to 1.39). The overall results indicate that oxcarbazepine is significantly better than phenytoin for time to treatment withdrawal, but suggest no overall difference between oxcarbazepine and phenytoin for other outcomes. Results stratified by seizure type indicate no significant advantage for either drug for patients with generalized onset seizures, but a potentially important advantage in time to withdrawal for oxcarbazepine for patients with partial onset seizures: HR 1.92 (95% CI 1.17 to 3.16). The age distribution of adults classified as having generalized epilepsy suggests a significant number of patients may have had their epilepsy misclassified.
AUTHORS' CONCLUSIONS: For patients with partial onset seizures oxcarbazepine is significantly less likely to be withdrawn, but current data do not allow a statement as to whether oxcarbazepine is equivalent, superior or inferior to phenytoin in terms of seizure control. Guidelines recommend carbamazepine as a first line treatment for patients with partial onset seizures and more evidence is needed regarding the comparative effects of oxcarbazepine and carbamazepine to further inform policy. For patients with generalized onset tonic-clonic seizures, valproate is considered the first line standard treatment and the results of this review do not inform current treatment policy. Misclassification of patients' epilepsy type may have confounded the results of this review.
在全球范围内，苯妥英是一种常用的抗癫痫药物。奥卡西平是较新的抗癫痫药物之一，其化学性质与其母体化合物卡马西平相似。对于像奥卡西平这样的新药，了解它们与标准治疗方法相比的情况很重要。
综述将奥卡西平和苯妥英作为癫痫患者单一疗法进行比较的最佳证据。
我们检索了Cochrane癫痫小组专业注册库（2005年12月）、Cochrane对照试验中央注册库（CENTRAL）（《Cochrane图书馆》2005年第3期）以及MEDLINE（1966年至2005年11月）。未设语言限制。我们检查了检索到的研究的参考文献列表，以获取相关研究的其他报告。我们还联系了制药公司，试图确定是否有未发表的研究。
针对儿童或成人癫痫患者的随机对照试验。试验必须包括奥卡西平单一疗法与苯妥英单一疗法的比较。
这是一项个体患者数据综述。两位综述作者独立评估试验质量并提取数据。与研究作者联系以获取更多信息。结局指标为：（a）接受分配治疗的时间；（b）达到6个月、12个月和24个月缓解的时间；（c）随机分组后首次发作的时间；（d）如有可用的生活质量测量指标。通过审查随机分组患者的特征、给药方案和试验设计等方面的差异来评估临床异质性。数据按意向性分析原则进行分析。使用分层对数秩检验来获得特定研究和总体的风险比估计值（及95%置信区间），其中风险比>1表明在苯妥英治疗组事件更有可能发生。
两项试验中有480例患者的个体患者数据可用，占符合我们纳入标准的两项试验招募患者的100%。按照惯例，对于停止分配治疗的时间和首次发作的时间这两个结局指标，风险比>1表明奥卡西平具有临床优势，而对于6个月和12个月缓解的时间，风险比>1表明苯妥英具有临床优势。主要总体结果（风险比，95%置信区间）为：（i）停止分配治疗的时间为1.64（1.09至2.47），（ii）6个月缓解的时间为0.89（0.66至1.22），（iii）12个月缓解的时间为0.92（0.62至1.37），（iv）首次发作的时间为1.07（0.83至1.39）。总体结果表明，在停止治疗的时间方面，奥卡西平明显优于苯妥英，但对于其他结局指标，奥卡西平和苯妥英之间总体无差异。按发作类型分层的结果表明，对于全身发作的患者，两种药物均无显著优势，但对于部分发作的患者，奥卡西平在停药时间方面可能具有重要优势：风险比为1.92（95%置信区间为1.17至3.16）。被归类为全身性癫痫的成人患者的年龄分布表明，可能有相当数量的患者癫痫分类错误。
对于部分发作的患者，奥卡西平停药的可能性显著更低，但目前的数据无法就奥卡西平在癫痫控制方面是否等同于、优于或劣于苯妥英做出说明。指南推荐卡马西平作为部分发作患者的一线治疗药物，关于奥卡西平和卡马西平比较效果的更多证据对于进一步指导决策很有必要。对于全身强直阵挛发作的患者，丙戊酸盐被视为一线标准治疗药物，本综述的结果无法为当前治疗决策提供参考。患者癫痫类型的错误分类可能混淆了本综述的结果。
