Spilker B, Bruni J, Jones M, Upton A, Cato A, Cloutier G
Epilepsia. 1983 Aug;24(4):410-21. doi: 10.1111/j.1528-1157.1983.tb04909.x.
Cinromide was evaluated versus placebo as add-on therapy in a double-blind crossover study in epileptic outpatients with partial seizures at three sites. Four-week base lines were used before, between, and after the two 12-week treatment periods of the crossover. An operational definition was used to classify each partial seizure as Type A, B, or C. Doses of concurrent antiepileptic drugs were adjusted to maintain pretreatment therapeutic plasma levels. Doses of cinromide ranged from 1,200 to 4,800 mg/day, depending on patient response. Seven patients were withdrawn from the study because of adverse experiences (two receiving placebo and five receiving cinromide). Twenty-eight patients completed the entire 36-week study. A decrease in the average frequency of seizures/week was observed in 12 patients receiving cinromide and in 16 patients receiving placebo. The median frequencies with cinromide and placebo were 3.3 and 2.9 seizures/week, respectively (median initial base-line frequency 3.5 seizures/week for all 28 patients). Although patients were randomly assigned to receive either cinromide or placebo first, the median base-line seizure frequency was greater at the start of the first treatment period in the cinromide group (4.3 versus 2.5 seizures/week) and greater at the start of the second treatment period in the placebo group (3.8 versus 1.4). The median seizure frequency in each higher group decreased with treatment, whereas it increased in each of the lower groups. This study did not demonstrate a beneficial effect of cinromide over placebo for Type A, B, or C partial seizures. The data suggested the presence of an oscillation of seizure frequency in our population of epileptic patients having partial seizures, as well as a placebo effect. No significant carry-over effects were observed. Cinromide has previously been shown to have significant antiepileptic activity in various animal models of epilepsy. The lack of an antiepileptic response to cinromide in humans may have been due to factors other than species differences but indicates that a positive results of a drug in animal models is not the sole factor necessary to predict beneficial antiepileptic activity in humans.
在一项三中心针对部分性发作癫痫门诊患者的双盲交叉研究中，对西诺米德作为附加疗法与安慰剂进行了评估。在交叉试验的两个12周治疗期之前、期间和之后，均采用了为期四周的基线期。使用操作性定义将每次部分性发作分为A、B或C型。调整同时使用的抗癫痫药物剂量，以维持治疗前的血浆治疗水平。西诺米德的剂量根据患者反应在1200至4800毫克/天之间。七名患者因不良事件退出研究（两名接受安慰剂，五名接受西诺米德）。28名患者完成了整个36周的研究。接受西诺米德治疗的12名患者和接受安慰剂治疗的16名患者每周癫痫发作平均频率有所下降。接受西诺米德和安慰剂治疗的患者癫痫发作中位数频率分别为每周3.3次和2.9次（所有28名患者的初始基线中位数频率为每周3.5次）。尽管患者被随机分配先接受西诺米德或安慰剂治疗，但西诺米德组在第一个治疗期开始时的基线癫痫发作频率中位数更高（每周4.3次对2.5次），而安慰剂组在第二个治疗期开始时更高（每周3.8次对1.4次）。每个较高组的癫痫发作中位数频率随治疗而降低，而每个较低组则升高。这项研究未证明西诺米德对A、B或C型部分性发作的疗效优于安慰剂。数据表明，在我们的部分性发作癫痫患者群体中存在癫痫发作频率的波动，以及安慰剂效应。未观察到显著的残留效应。西诺米德此前已在各种癫痫动物模型中显示出显著的抗癫痫活性。在人类中对西诺米德缺乏抗癫痫反应可能是由于物种差异以外的因素，但表明药物在动物模型中的阳性结果并非预测其在人类中有益抗癫痫活性的唯一必要因素。
