Piña-Garza J E, Levisohn P, Gucuyener K, Mikati M A, Warnock C R, Conklin H S, Messenheimer J
Vanderbilt University, Children's Hospital at Vanderbilt, Nashville, TN 37232-9559, USA.
Neurology. 2008 May 27;70(22 Pt 2):2099-108. doi: 10.1212/01.wnl.0000285493.08622.35. Epub 2007 Dec 12.
This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months.
The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained.
The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients.
Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.
本随机、双盲、安慰剂对照试验旨在评估辅助使用拉莫三嗪治疗1至24个月婴儿部分性癫痫发作的疗效和耐受性。
该研究采用了富集反应者设计，所有患者在开放标签阶段接受辅助拉莫三嗪治疗（n = 177；对于使用非酶诱导抗癫痫药物[AEDs]或丙戊酸盐的患者，最大维持剂量为5.1 mg/kg/天，对于使用酶诱导AEDs的患者，最大维持剂量为15.6 mg/kg/天）。符合反应标准的患者被随机分配接受长达8周的双盲治疗，继续使用拉莫三嗪（n = 19）或停用拉莫三嗪（安慰剂；n = 19），同时维持背景AEDs治疗。
拉莫三嗪组治疗失败（符合退出标准或在完成双盲阶段前退出的患者）的比例（58%）低于安慰剂组（84%）。这一发现在主要分析（双侧卡方检验[主要终点]）中无统计学意义。还对主要终点进行了事后敏感性分析（单侧、经中p校正的Fisher精确检验，p = 0.045）。达到退出标准的中位时间，拉莫三嗪组（42天）长于安慰剂组（22天）（p = 0.059）。在开放标签阶段的最后28天，53%使用拉莫三嗪的患者部分性癫痫发作频率降低≥50%。与开放标签阶段的最后4周相比，在双盲阶段，随机分配接受拉莫三嗪治疗的患者部分性癫痫发作频率进一步降低（32%降低≥25%），而随机分配接受安慰剂治疗的患者未出现进一步降低（5%降低≥25%）。拉莫三嗪耐受性良好，不良事件谱与较大儿童患者中观察到的相似。
拉莫三嗪耐受性良好，数据表明其可能对1至24个月婴儿的部分性癫痫发作有效。
