Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojärvi J
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA.
Neurology. 2006 Aug 8;67(3):400-6. doi: 10.1212/01.wnl.0000232737.72555.06.
To compare the cognitive effects of lamotrigine vs topiramate as adjunctive therapy in adults with epilepsy.
A multicenter, double-blind, randomized, prospective study was conducted in adults with partial seizures. Lamotrigine or topiramate was introduced as an adjunctive therapy to carbamazepine or phenytoin and titrated over 8 weeks to target doses. These drugs were maintained another 8 weeks (maintenance phase) without dosage changes. The primary endpoint was change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition (Controlled Oral Word Association Task [COWA]; Stroop Color-Word Interference; Digit Cancellation; Lafayette Grooved Pegboard, dominant hand; Rey Auditory Verbal Learning Test, delayed recall; and Symbol-Digit Modalities test).
For the primary endpoint, cognitive performance at the end of the maintenance phase was better with lamotrigine than with topiramate (415.3 vs 315.1; p < 0.001). On the individual cognitive tests, performance was better with lamotrigine than with topiramate in mean changes from screening on the COWA (p < 0.001), Stroop Color-Word Interference (p = 0.038), and Symbol-Digit Modalities tests (p < 0.001). The treatment effect exceeded the minimum clinically important difference for the COWA and the Symbol-Digit Modalities test. Mean changes from screening in the Performance-On-Line test simulating driving skills reflected better performance with lamotrigine than with topiramate (p = 0.021). The median percentage change from baseline in seizure frequency was lower with lamotrigine than with topiramate during the escalation phase (-80% vs -100%; p = 0.028) but not during the maintenance phase (-75% vs -100%; p = 0.062). The frequencies of cognitive adverse events and of premature withdrawals related to cognitive decline were higher with topiramate than with lamotrigine (6% vs 0%; p = 0.013).
Lamotrigine had significantly less impact than topiramate on measures of cognition when used as adjunctive therapy for partial seizures.
比较拉莫三嗪与托吡酯作为成人癫痫辅助治疗药物时的认知效果。
对部分性发作的成人患者进行了一项多中心、双盲、随机、前瞻性研究。将拉莫三嗪或托吡酯作为卡马西平或苯妥英钠的辅助治疗药物，并在8周内滴定至目标剂量。这些药物在无剂量变化的情况下再维持8周（维持期）。主要终点是在认知标准化测量（受控口语单词联想任务[COWA]；斯特鲁普颜色-单词干扰；数字划消；拉法叶有槽钉板，优势手；雷氏听觉词语学习测验，延迟回忆；以及符号-数字模式测验）的综合分析中，从筛查到维持期末的变化。
对于主要终点，维持期末拉莫三嗪组的认知表现优于托吡酯组（415.3对315.1；p<0.001）。在各项认知测试中，拉莫三嗪组在COWA（p<0.001）、斯特鲁普颜色-单词干扰（p=0.038）和符号-数字模式测验（p<0.001）中从筛查开始的平均变化方面表现优于托吡酯组。治疗效果超过了COWA和符号-数字模式测验的最小临床重要差异。模拟驾驶技能的在线表现测试中从筛查开始的平均变化显示，拉莫三嗪组的表现优于托吡酯组（p=0.021）。在剂量递增期，拉莫三嗪组癫痫发作频率较基线的中位百分比变化低于托吡酯组（-80%对-100%；p=0.028），但在维持期并非如此（-75%对-100%；p=0.062）。托吡酯组与认知下降相关的认知不良事件和提前退出的频率高于拉莫三嗪组（6%对0%；p=0.013）。
作为部分性发作的辅助治疗药物，拉莫三嗪对认知测量的影响明显小于托吡酯。
