Walker J E, Homan R W, Crawford I L
Epilepsia. 1984 Aug;25(4):464-6. doi: 10.1111/j.1528-1157.1984.tb03444.x.
Lorazepam was studied in a double-blind, placebo-controlled, crossover trial in eight patients with frequent partial complex seizures refractory to therapy with a combination of standard anticonvulsant drugs. Concomitant antiepileptic drugs were maintained at therapeutic serum levels throughout the study, and concentrations of lorazepam were monitored. Following an 8-week baseline observation, patients were randomly assigned to placebo or lorazepam (1 mg BID). The dose was increased biweekly until seizures stopped or unacceptable side effects occurred. Eight weeks later, patients were crossed over, and the same escalating dose paradigm was followed. When seizure frequency during the last 2 weeks of each treatment was compared, seven of eight patients had fewer seizures on lorazepam, and the eighth had decreased seizure duration (a significant difference: p less than 0.01, two-tailed sign test). Blood level data suggest a narrow therapeutic window, with seizure improvement occurring at concentrations of 20-30 ng/ml and side effects at greater than 33 ng/ml. Lorazepam appears to be a useful adjunct in refractory partial complex seizure therapy. It should not be stopped abruptly, as an increase in seizure frequency may result.
在一项双盲、安慰剂对照、交叉试验中，对8例频繁发作的部分性复杂性癫痫患者进行了研究，这些患者对标准抗惊厥药物联合治疗无效。在整个研究过程中，维持抗癫痫药物的血清治疗水平，并监测劳拉西泮的浓度。经过8周的基线观察后，患者被随机分配接受安慰剂或劳拉西泮（1毫克，每日两次）治疗。剂量每两周增加一次，直至癫痫发作停止或出现无法耐受的副作用。8周后，患者进行交叉治疗，并遵循相同的剂量递增模式。当比较每种治疗最后2周的癫痫发作频率时，8例患者中有7例服用劳拉西泮后癫痫发作减少，第8例患者的癫痫发作持续时间缩短（差异有统计学意义：p<0.01，双侧符号检验）。血药浓度数据表明治疗窗较窄，癫痫发作改善发生在浓度为20-30纳克/毫升时，而浓度大于33纳克/毫升时会出现副作用。劳拉西泮似乎是难治性部分性复杂性癫痫治疗的一种有用辅助药物。不应突然停药，否则可能导致癫痫发作频率增加。
