The pharmacological treatment of epilepsy:recent advances and future perspectives

The pharmacological armamentarium against epilepsy has expanded considerably over the last three decades,and currently includes over 30 different antiseizure medications.Despite this large armamentarium,about one third of people with epilepsy fail to achieve sustained seizure freedom with currently available medications.This sobering fact,however,is mitigated by evidence that clinical outcomes for many people with epilepsy have improved over the years.In particular,physicians now have unprecedented opportunities to tailor treatment choices to the characteristics of the individual,in order to maximize efficacy and tolerability.The present article discusses advances in the drug treatment of epilepsy in the last 5 years,focusing in particular on comparative effectiveness trials of second-generation drugs,the introduction of new pharmaceutical formulations for emergency use,and the results achieved with the newest medications.The article also includes a discussion of potential future developments,including those derived from advances in information technology,the development of novel precision treatments,the introduction of disease modifying agents,and the discovery of biomarkers to facilitate conduction of clinical trials as well as routine clinical management.

发展中国家的癫痫治疗 药物便宜而有效,但大部分患者未接受治疗

生活在发展中国家的3500万癫痫患者中，大约85％根本未接受过任何治疗。其结果是，这些患者不仅会发生癫痫发作，而且还会产生自卑心理，忍受社会歧视。遗憾的是，绝大多数患者，其中大部分是儿童，可以通过每天口服1次价值低于3美元（合1．50英镑；2．20欧元）的药物而完全得到控制并能够恢复正常生活。在本期BMJ中（见第272页），来自孟加拉国的Banu及其同事对卡马西平和苯巴比妥在108名儿童癫痫患者治疗中的疗效和行为学副作用进行了随机对照研究。

Ⅲ期临床试验非盲延期阶段联合使用吡仑帕奈的局灶性癫痫患者的四年药物安全性、耐受性及发作结局:307号研究

评估307号研究(临床试验验证码:NCT00735397)Ⅲ期非盲延期阶段(OLEx)联合使用吡仑帕奈的局灶性癫痫患者的药物安全性、耐受性及痫性发作结局。患者在完成任一III期双盲试验后均可进入非盲延期阶段(Open-labelextension,OLEx)。对所有OLEx队列中有同样最小吡伦帕奈暴露剂量的局灶性癫痫和继发全面性癫痫(Secondarily generalized seizures,SGS)的患者进行药物安全性及耐受性和痫性发作结局(每28 d中位痫性发作减少率、反应率和无发作率)的分析。另外,针对OLEx的早期失访进行了额外的敏感性分析。从1480例双盲试验中随机分组的患者共纳入1218例。大部分患者(65.4%~80.9%)仅用吡仑帕奈12 mg,每日一次,进行治疗,并在相同剂量下完成长期的检测,或是相对基线联合使用少量抗癫痫药物(AEDs)。长期的药物安全性及耐受性结果与双盲研究一致。导致超过1%的患者研究中断治疗的紧急不良反应事件(Treatment-emergent adverse events,TEAEs)包括眩晕、易激、疲劳。有临床意义的TEAEs稳定期为4年。所有队列中患者的痫性发作结局随时间持续改善。对于接受3年(n=436)、4年(n=78)药物治疗的患者28 d中位痫性发作减少率分别为62%、70.6%,相应的50%反应率为59.6%、67.9%。最大28 d中位痫性发作减少率发生于基线水平的SGS患者,接受3年(n=190)、4年(n=28)药物治疗分别为88.0%和100.0%。在这些队列中分别有40.0%和53.6%的患者达到了无SGS。排除早期失访后的28 d中位痫性发作减少率结果类似。长期吡仑帕奈联合用药(≤4年)不会导致新的药物安全性及耐受性问题,并且可以很大程度地减少痫性发作,特别是基线水平的SGS患者。