Baulac M
Service de Neurologie, Epilepsie, Hôpital de la Pitié-Salpêtrière, 47 Bd de l'hôpital, 75013 Paris France.
Rev Neurol (Paris). 2002 May;158(5 Pt 2):4S46-54.
Introduction of new generation antiepileptic drugs on the French market has considerably diversified our conventional therapeutic schemes for epilepsy. New arrivals, topiramate, tiagabine and oxcarbazepine, will further amplify these changes. Compared with conventional drugs, these new products present more favorable pharmacokinetic properties, with no or very weak interactions and better tolerability, especially concerning cognition. These new agents should be used in accordance with their spectrum of activity, which depends on their mechanism of action. In add-on trials in partial epilepsy patients, all these new products have shown efficacy in partial and secondarily generalized seizures. Seizure frequency is reduced by at least 50% in 30 to 50% of the patients. Some of these drugs have a broader spectrum, also exhibiting efficacy for the different seizure types of generalized, symptomatic or idiopathic epilepsy. Gabamimetic agents may have worsening effects in some patients with generalized epilepsy, especially with absence or myoclonic seizures. The most obvious benefits, some patients become seizure-free, are obtained in patients with intermediate severity given a two-drug regimen including one of these new agents. For children progress has been less rapid but prognosis, including cognitive outcome, has been considerably improved, for example in infantile spasms with vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the latter drug being highly toxic. For the moment in France, authorities have limited the use of all these new antiepileptic drugs to adjunctive therapy for epilepsy resistant to conventional drugs. Recent monotherapy data have however demonstrated similar efficacy and better tolerability. Once the pivotal, controlled studies have enabled regulatory approval, all these compounds will have to undergo large-scale evaluation in order to better define dosages, long-term tolerability, indications and possible contra-indications in the various epileptic syndromes, including childhood epilepsy.
新一代抗癫痫药物在法国市场的引入，使我们治疗癫痫的传统方案有了显著的多样化。新上市的托吡酯、噻加宾和奥卡西平将进一步扩大这些变化。与传统药物相比，这些新产品具有更有利的药代动力学特性，相互作用少或非常弱，耐受性更好，尤其是在认知方面。这些新药应根据其活性谱使用，这取决于它们的作用机制。在部分癫痫患者的附加试验中，所有这些新产品在部分性发作和继发性全身性发作中均显示出疗效。30%至50%的患者癫痫发作频率至少降低了50%。其中一些药物的活性谱更广，对全身性、症状性或特发性癫痫的不同发作类型也有疗效。拟γ-氨基丁酸类药物对一些全身性癫痫患者可能有恶化作用，尤其是失神或肌阵挛发作患者。最明显的益处是，一些患者实现了无癫痫发作，这在中度严重程度的患者中使用包含一种新药的两药联合方案时可以获得。对于儿童，进展较为缓慢，但预后，包括认知结果，已得到显著改善，例如在使用氨己烯酸治疗婴儿痉挛症以及使用拉莫三嗪和非氨酯治疗伦诺克斯-加斯托综合征时，后者毒性很大。目前在法国，当局已将所有这些新型抗癫痫药物的使用限制为对传统药物耐药的癫痫的辅助治疗。然而，最近的单药治疗数据显示了相似的疗效和更好的耐受性。一旦关键的对照研究获得监管批准，所有这些化合物都将必须进行大规模评估，以便更好地确定各种癫痫综合征（包括儿童癫痫）中的剂量、长期耐受性、适应症和可能的禁忌症。
