Kinirons P, McCarthy M, Doherty C P, Delanty N
Division of Epilepsy, Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
Seizure. 2006 Sep;15(6):387-92. doi: 10.1016/j.seizure.2006.05.001.
Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients.
We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'.
344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders.
A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.
左乙拉西坦（LEV）已被批准作为成年部分性癫痫患者的附加治疗药物。从临床试验中可以明显看出，高达8%的先前耐药患者通过添加左乙拉西坦可能实现无癫痫发作。目前尚无办法预测这些意外有反应的患者。我们着手识别那些先前难治但对左乙拉西坦附加治疗表现出意外反应的患者，并将他们与未对该药物产生反应的患者进行比较。然后我们试图描述区分这些患者组的任何临床特征。
我们纳入了所有有当前或先前使用左乙拉西坦病史且对至少两种其他先前抗癫痫药物（AEDs）无反应的患者，并记录他们的人口统计学和临床数据。我们将反应分为：（a）“无癫痫发作”（开始使用左乙拉西坦后至少6个月无癫痫发作）；（b）“部分发作减少>50%”（开始使用左乙拉西坦后癫痫发作减少超过50%且持续至少6个月）；（c）“蜜月期”（开始使用左乙拉西坦后无癫痫发作少于6个月，然后恢复到基线频率）；以及（d）“无反应”。为了分析目的，我们将“无癫痫发作”和“部分发作减少>50%”组视为“有反应者”，将“无反应”组视为“无反应者”。
344名患者纳入分析。56名患者（16.3%）使用左乙拉西坦后实现无癫痫发作。特发性全身性癫痫和创伤后部分性癫痫在有反应者组比无反应者组更常见（分别为p = 0.005和0.05）。与无反应者相比，有反应者更常将拉莫三嗪与左乙拉西坦联合使用（p = 0.003）。有反应者的左乙拉西坦平均每日剂量低于无反应者。
通过左乙拉西坦附加治疗，先前耐药患者实现无癫痫发作的人数高于预期。那些反应最佳的患者似乎在相对较低剂量时就有反应，我们的数据表明左乙拉西坦与拉莫三嗪之间可能存在有益的药效学相互作用。我们无法识别任何能明确预测哪些患者会实现无癫痫发作的临床因素，我们推测反应可能由遗传或分子因素决定。所有耐药患者，包括那些正在接受手术评估的患者，无论其癫痫分类如何，都应考虑进行左乙拉西坦试验。
