Beran Roy G, Berkovic Samuel F, Black Andrew B, Danta Gytis, Hiersemenzel Reinhard, Schapel Graham J, Vajda Frank J E
Strategic Health Evaluators and University of New South Wales, 12 Thomas Street, Suite 5, 6th Floor, Chatswood, NSW 2067, Australia.
Epilepsy Res. 2005 Jan;63(1):1-9. doi: 10.1016/j.eplepsyres.2004.09.005. Epub 2005 Jan 6.
To evaluate the efficacy and tolerability of levetiracetam as add-on therapy in patients with refractory partial-onset seizures in a protocol designed to reflect clinical practice.
All patients in this open-label, single-arm study entered an 8-week baseline period followed by a 4-week titration period and a 12-week maintenance period. Patients initially received levetiracetam 1000 mg/day (administered bid) and could increase to 2000 mg/day after 2 weeks, and to 3000 mg/day after another 2 weeks, to obtain adequate seizure control. During the 12-week maintenance period, the dose of levetiracetam could not be increased but could be decreased once if tolerability warranted. Seizure count and adverse events were recorded by patients in a diary. Quality of life and global evaluation of disease evolution were also evaluated.
Ninety-nine patients were enrolled and 91 completed the study. A steady dose was maintained over the last 8 weeks of treatment or longer in 84 patients, with 89.3% of these patients receiving 3000 mg/day, 9.5% receiving 2000 mg/day, and 1.2% receiving 1000 mg/day. A 35.9% median percent reduction from baseline in weekly frequency of partial-onset seizures was observed over the entire treatment period. The median partial-onset seizure count decreased from 2.3 per week during the baseline period to 1.3 per week over the treatment period. A total of 42.4% of patients were responders (> or = 50% reduction from baseline in weekly seizure frequency) over the treatment period; two patients were seizure-free from the first day of treatment throughout the treatment period. The most frequent drug-related adverse events were fatigue (27.3% of patients), somnolence (11.1%), headache (8.1%), and dizziness (8.1%).
Levetiracetam as add-on therapy at doses up to 3000 mg/day effectively reduced the frequency of partial-onset seizures in patients with refractory epilepsy and was well-tolerated in this study, bridging conditions of placebo-controlled clinical trials and clinical practice.
在一项旨在反映临床实践的方案中，评估左乙拉西坦作为难治性部分性发作患者附加治疗的疗效和耐受性。
在这项开放标签、单臂研究中，所有患者进入为期8周的基线期，随后是为期4周的滴定期和为期12周的维持期。患者最初接受左乙拉西坦1000毫克/天（每日两次给药），2周后可增至2000毫克/天，再过2周后可增至3000毫克/天，以获得充分的癫痫发作控制。在12周的维持期内，左乙拉西坦的剂量不能增加，但如果耐受性允许，可降低一次。患者在日记中记录癫痫发作次数和不良事件。还评估了生活质量和疾病进展的整体评估。
99名患者入组，91名完成研究。84名患者在治疗的最后8周或更长时间内维持稳定剂量，其中89.3% 的患者接受3000毫克/天，9.5% 接受2000毫克/天，1.2% 接受1000毫克/天。在整个治疗期间，观察到部分性发作的每周频率较基线中位数降低了35.9%。部分性发作的中位数从基线期的每周2.3次降至治疗期的每周1.3次。在治疗期间，共有42.4% 的患者有反应（每周癫痫发作频率较基线降低≥50%）；两名患者从治疗第一天起在整个治疗期间无癫痫发作。最常见的药物相关不良事件是疲劳（27.3% 的患者）、嗜睡（11.1%）、头痛（8.1%）和头晕（8.1%）。
左乙拉西坦作为附加治疗，剂量高达3000毫克/天，可有效降低难治性癫痫患者部分性发作的频率，且在本研究中耐受性良好，弥合了安慰剂对照临床试验和临床实践的情况。
