Yamamoto Takamichi, Yamazoe Tomohiro, Fujimoto Ayataka, Kobayashi Rieko, Yokota Takuya, Okanishi Toru, Uchiyama Go, Ohashi Toshihiko, Tanaka Tokutaro, Enoki Hideo
Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital.
Brain Nerve. 2014 Jan;66(1):59-69.
Lamotrigine (LTG) has been recognized as one of the best newer antiepileptic drugs (AEDs) used in developed countries since 1991. A retrospective study was carried out to evaluate the efficacy, adverse reactions, and other peculiarities of LTG. Two hundred and eighty-one patients with epilepsy, aged 16 or more, were treated with LTG between December 2008 and December 2012 at the Seirei Hamamatsu General Hospital. One hundred and forty patients were found to be eligible to evaluate the effectiveness of LTG. Of them, 100 patients had localized epilepsy, and 40 patients had generalized epilepsy. Seventy-five out of these 140 (53.6%) patients obtained seizure freedom following LTG use, and 24 patients (17.1%) showed more than 50% seizure reduction, which indicates that a total of 99 patients (70.7%) were good responders. A seizure reduction of less than 50% was seen in 8 patients (5.7%), whereas 30 patients (21.4%) did not display any obvious seizure reduction. Three patients (2.1%) showed a worsening of seizure frequency. Patients with idiopathic generalized epilepsy such as juvenile myoclonic epilepsy showed satisfactory results. Many good responders were also patients with stroke or brain tumor. The number of concomitant AEDs used demonstrated a more distinctive feature. Monotherapy without any other AEDs was used in 20 patients. LTG was used as an add-on with 1 concomitant AED in 59 patients (42.1%) and as an add-on with 2 concomitant AEDs in 37 patients (26.4%). Thus, a large number of patients (68.6%) underwent early add-on treatment. LTG as an add-on in concert with concomitant AEDs contributed to the excellent results in terms of seizure reduction observed in this study. LTG administration requires established titration, particularly to prevent drug eruption. Over 60% of the patients were treated by slower titration than that used in the established titration method. However, seizure freedom was accomplished within 1-5 weeks from the beginning of LTG treatment with doses much lower than 200 mg/day, which indicated the effectiveness of low-dose LTG in the early phase of treatment. The average maintenance dose was 162.7 mg/day; however, half of the patients maintained their dose at more than 200 mg/day. The continuation rate was 77.2%. The main reasons for withdrawal were dissatisfaction with drug effectiveness and drug eruption. However, the incidence of drug eruption was only in 15 out of 281 (5.3%) patients, which is similar to previously reported rates. Therefore, LTG is an effective and safe AED. Moreover, it is a promising drug for promoting a paradigm shift towards newer AEDs. LTG administration as a first add-on AED is strongly recommended to obtain excellent results and to maintain good compliance with the epilepsy treatment course.
自1991年以来,拉莫三嗪(LTG)已被公认为发达国家使用的最佳新型抗癫痫药物(AEDs)之一。开展了一项回顾性研究,以评估LTG的疗效、不良反应及其他特性。2008年12月至2012年12月期间,静冈清水综合医院对281例16岁及以上的癫痫患者使用了LTG进行治疗。发现140例患者符合评估LTG疗效的条件。其中,100例患者患有局灶性癫痫,40例患者患有全身性癫痫。这140例患者中有75例(53.6%)在使用LTG后实现无癫痫发作,24例患者(17.1%)癫痫发作减少超过50%,这表明共有99例患者(70.7%)反应良好。8例患者(5.7%)癫痫发作减少不到50%,而30例患者(21.4%)未表现出明显的癫痫发作减少。3例患者(2.1%)癫痫发作频率增加。特发性全身性癫痫患者(如青少年肌阵挛性癫痫)取得了满意的结果。许多反应良好的患者也是中风或脑肿瘤患者。同时使用的AEDs数量表现出更显著的特征。20例患者未使用任何其他AEDs进行单药治疗。59例患者(42.1%)将LTG作为一种添加药物与1种同时使用的AEDs联合使用,37例患者(26.4%)将LTG作为一种添加药物与2种同时使用的AEDs联合使用。因此,大量患者(68.6%)接受了早期添加治疗。在本研究中观察到,LTG作为添加药物与同时使用的AEDs联合使用在减少癫痫发作方面取得了优异的效果。服用LTG需要确定滴定方法,特别是为了预防药疹。超过60%的患者采用了比既定滴定方法更慢的滴定方式进行治疗。然而,在开始使用LTG治疗后的1 - 5周内,使用远低于200mg/天的剂量就实现了无癫痫发作,这表明低剂量LTG在治疗早期是有效的。平均维持剂量为162.7mg/天;然而,一半的患者维持剂量超过200mg/天。持续治疗率为77.2%。停药的主要原因是对药物疗效不满意和药疹。然而,药疹的发生率仅为281例患者中的15例(5.3%),这与先前报道的发生率相似。因此,LTG是一种有效且安全的AED。此外,它是一种有望推动向新型AEDs模式转变的药物。强烈建议将LTG作为第一种添加的AEDs使用,以获得优异的效果并保持对癫痫治疗过程的良好依从性。