Sachdeo R C, Leroy R F, Krauss G L, Drake M E, Green P M, Leppik I E, Shu V S, Ringham G L, Sommerville K W
Department of Neurology, University of Medicine and Dentistry of New Jersey, New Brunswick 08901-2160, USA.
Arch Neurol. 1997 May;54(5):595-601. doi: 10.1001/archneur.1997.00550170069016.
To evaluate the efficacy and safety of 2 regimens of tiagabine as add-on therapy for patients with complex partial seizures (CPSs) that are refractory to other treatment.
Randomized, double-blind, placebo-controlled, add-on, parallel-group trial with an 8-week baseline period, 12-week experimental period (4 weeks of dose titration and 8 weeks of fixed-dose therapy), and 4-week termination period.
Twenty-six centers throughout the United States.
Three hundred fifty-one patients were enrolled, 318 were entered in the double-blind period, and 271 completed the study.
Tiagabine, 16 mg 2 times per day (106 patients); tiagabine, 8 mg 4 times daily (105 patients); and placebo (107 patients). The doses of tiagabine were titrated in 3 steps to the fixed dose.
The median change in the 4-week rate of CPSs from baseline to experimental period.
The median change from baseline was -1.6 CPSs per 4 weeks in the group of patients who were given tiagabine 2 times per day, and it was -1.2 CPSs in the group of patients who were given tiagabine 4 time per day (P = .06 and P = .02, respectively, compared with placebo). The 4-week seizure frequency was reduced by 50% or more in 31% of the patients who were given tiagabine 2 times per day and in 27% of the patients who were given tiagabine 4 times per day vs 10% of the placebo-treated patients (P < or = .001 for each tiagabine-treated group compared with the placebo group). The most frequent adverse events involved the central nervous system and occurred in comparable proportions in the 3 treatment groups. Similar proportions of patients discontinued the study prematurely for adverse events.
Tiagabine administered 2 and 4 times daily as add-on pharmacotherapy was effective in reducing CPSs in patients with epilepsy whose conditions were refractory to treatment with other antiepileptic agents, and it was well tolerated.
评估两种噻加宾给药方案作为添加疗法治疗对其他治疗无效的复杂部分性发作（CPS）患者的疗效和安全性。
随机、双盲、安慰剂对照、添加、平行组试验，有8周的基线期、12周的试验期（4周剂量滴定和8周固定剂量治疗）以及4周的终止期。
美国各地的26个中心。
共纳入351例患者，318例进入双盲期，271例完成研究。
噻加宾，每日2次，每次16mg（106例患者）；噻加宾，每日4次，每次8mg（105例患者）；以及安慰剂（107例患者）。噻加宾剂量分3步滴定至固定剂量。
从基线期到试验期4周内CPS发生率的中位数变化。
每日服用2次噻加宾的患者组从基线期的中位数变化为每4周 -1.6次CPS，每日服用4次噻加宾的患者组为每4周 -1.2次CPS（与安慰剂相比，P值分别为0.06和0.02）。每日服用2次噻加宾的患者中有31%、每日服用4次噻加宾的患者中有27%的4周癫痫发作频率降低了50%或更多，而安慰剂治疗的患者中这一比例为10%（每个噻加宾治疗组与安慰剂组相比，P≤0.001）。最常见的不良事件累及中枢神经系统，在3个治疗组中的发生率相当。因不良事件提前终止研究的患者比例相似。
每日2次和4次给药的噻加宾作为添加药物疗法，对于对其他抗癫痫药物治疗无效的癫痫患者，在减少CPS方面有效，且耐受性良好。
