Arroyo S, Dodson W E, Privitera M D, Glauser T A, Naritoku D K, Dlugos D J, Wang S, Schwabe S K, Twyman R E
Department of Neurology, Hospital Clinico de Barcelona, Barcelona, Spain.
Acta Neurol Scand. 2005 Oct;112(4):214-22. doi: 10.1111/j.1600-0404.2005.00485.x.
To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design.
We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized.
Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months.
Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.
采用剂量对照研究设计评估托吡酯单药治疗的疗效和耐受性。
我们对成人及儿童（≥6岁）癫痫患者进行了一项多国、随机、双盲试验，这些患者在随机分组时未接受治疗，被随机分配至400或50毫克/天的托吡酯作为目标维持剂量。除了终身有≥2次无诱因发作外，患者在3个月回顾性基线期必须有1次或2次部分性发作或全面性强直阵挛发作。主要疗效终点是首次发作时间；次要疗效指标是6个月和1年时的无发作率。双盲治疗持续至最后一名患者随机分组后6个月。
对于首次发作时间的Kaplan-Meier生存分析（意向性治疗，n = 470）显示，作为目标维持剂量，400毫克/天优于50毫克/天（P = 0.0002）。首次出现显著差异（P = 0.046）且支持较高剂量的评估点是在第14天，此时患者接受100或25毫克/天的剂量。随机分配至400毫克/天的患者在6个月时无发作的概率为83%，随机分配至50毫克/天的患者为71%（P = 0.005）。12个月时的无发作率分别为76%和59%（P = 0.001）。在部分性发作患者（P = 0.009）和全面性强直阵挛发作患者（P = 0.005）中，支持较高剂量组的差异显著。最常见的剂量相关不良事件是感觉异常、体重减轻和食欲减退。因认知相关不良事件而停药的比例在50毫克组为2%，在400毫克组为7%。总体而言，在中位治疗期9个月期间，分别有7%和19%的患者因不良事件停药。
托吡酯对成人和儿童单药治疗有效。由于在滴定过程中出现治疗效果，临床医生应以逐步方式调整剂量，设置中间停药点，例如100毫克/天，以评估患者反应并达到最佳维持剂量。
