Grant R, Shorvon S D
Department of Clinical Neurosciences, The University of Edinburgh, Western General Hospitals NHS Trust, Crewe Road, EH4 2XU, Edinburgh, UK.
Epilepsy Res. 2000 Dec;42(2-3):89-95. doi: 10.1016/s0920-1211(00)00158-3.
The aim of this study was to determine the efficacy and tolerability of 1000-4000 mg/day of levetiracetam (LEV, Keppra) as add-on treatment for refractory epilepsy. This was a dose-escalation study of 29 patients with refractory epilepsy. Patients received placebo for 4 weeks (baseline) followed by levetiracetam 1000 and 2000 mg per day each for 2 weeks, and then 3000 and 4000 mg per day each for 4 weeks. Primary efficacy was assessed by seizure frequency (number/week). Tolerability was assessed by adverse events, laboratory parameters, clinical evaluations, and electrocardiogram. All the study periods were completed by 27 of the 29 patients. A substantially lower median seizure frequency was observed at all levetiracetam dosing periods (1000 mg per day, 1.0 seizures per week; 2000 mg per day, 1.5 seizures per week; 3000 mg per day, 1.0 seizures per week; 4000 mg per day, 0.75 seizures per week) compared with the placebo treatment (2.06 seizures per week). In addition, 22-33% of these patients were seizure free during treatment with levetiracetam compared with only 14% with placebo. Levetiracetam was well tolerated. The most common adverse events were somnolence and asthenia; frequency and severity increased with increasing doses of levetiracetam. Levetiracetam in doses from 1000 to 4000 mg per day is effective. Somnolence and asthenia were more frequent with the highest dose, suggesting that 4000 mg per day may be the upper limit in some patients, although individual susceptibility to somnolence was variable.
本研究的目的是确定每日1000 - 4000毫克左乙拉西坦（LEV，开浦兰）作为难治性癫痫附加治疗的疗效和耐受性。这是一项针对29例难治性癫痫患者的剂量递增研究。患者接受4周的安慰剂治疗（基线期），随后每日服用1000毫克和2000毫克左乙拉西坦各2周，然后每日服用3000毫克和4000毫克各4周。主要疗效通过癫痫发作频率（次数/周）进行评估。耐受性通过不良事件、实验室参数、临床评估和心电图进行评估。29例患者中有27例完成了所有研究阶段。在所有左乙拉西坦给药期（每日1000毫克，每周发作1.0次；每日2000毫克，每周发作1.5次；每日3000毫克，每周发作1.0次；每日4000毫克，每周发作0.75次）观察到的癫痫发作频率中位数显著低于安慰剂治疗期（每周发作2.06次）。此外，这些患者在左乙拉西坦治疗期间有22% - 33%无癫痫发作，而安慰剂组仅为14%。左乙拉西坦耐受性良好。最常见的不良事件是嗜睡和乏力；随着左乙拉西坦剂量增加，其发生频率和严重程度增加。每日剂量为1000至4000毫克的左乙拉西坦是有效的。最高剂量时嗜睡和乏力更为频繁，这表明尽管个体对嗜睡的易感性存在差异，但对于某些患者而言，每日4000毫克可能是上限。
