Bethel Epilepsy Centre, Teilanstalt Bethel, Bielefeld, Germany.
Clin Drug Investig. 1998;16(4):263-77. doi: 10.2165/00044011-199816040-00001.
This study evaluated the effects of lamotrigine in routine therapy in the highly selected clientele of the Residential Department of the Bethel Epilepsy Centre.
In an open, observational, add-on study design, 125 resident patients with severe therapy-resistant epilepsy and multiple additional handicaps were treated with lamotrigine in titrated doses. Seizure types, monthly seizure frequency, seizure severity, and psychological status were recorded during a 3-month baseline and a 3-month lamotrigine treatment period prior to the key date of this analysis (31 March 1996).
At the time of analysis, the mean lamotrigine dosage was 391 mg/day (mean serum concentration 4.25 mg/L). 71.4% of the patients (after a mean observation time of 21.9 months) were still receiving lamotrigine. In the remaining 28.6%, the main reasons for withdrawal (after a mean of 10.5 months) were lack of effectiveness (19 patients, 15.2%), increase in seizure frequency (8 patients, 6.4%), and negative psychotropic effects (5 patients, 4.0%). On an intention-to-treat basis, the responder rate (reduction in seizure frequency by 50% or more) was 28.8% (35.6% in focal epilepsy, 26.7% in generalised epilepsy, and 22.4% in epilepsy with focal and generalised seizures). Seizure reduction was similar for all seizure types. Lamotrigine was more effective when combined with valproic acid (p < 0.005) and less effective when combined with carbamazepine or phenytoin. Stepwise multivariate logistic regression revealed valproic acid (and not lamotrigine dose or concentration, co-medication, epileptic syndrome, or seizure type) as the only factor predicting seizure response. 28.0% of the patients had shorter and/or less severe seizures, and 8.8% had longer/more severe seizures. 25.6% experienced a positive and 8.0% a negative psychotropic effect (mostly aggression). In all, 53.6% of patients benefited according to the three efficacy criteria, and 8.8% deteriorated. The most frequent dose-dependent adverse effects were ataxia, dizziness and diplopia.
Lamotrigine was an effective and well tolerated drug for this special patient group, especially when combined with valproic acid.
本研究评估了拉莫三嗪在贝特尔癫痫中心住院部高度选择的患者常规治疗中的作用。
在一项开放、观察性、附加研究设计中，125 名患有严重治疗抵抗性癫痫和多种额外残疾的住院患者接受了拉莫三嗪滴定剂量治疗。在本次分析的关键日期（1996 年 3 月 31 日）之前的 3 个月基线期和 3 个月拉莫三嗪治疗期内，记录了癫痫发作类型、每月癫痫发作频率、癫痫发作严重程度和心理状态。
在分析时，拉莫三嗪的平均剂量为 391mg/天（平均血清浓度 4.25mg/L）。71.4%的患者（平均观察时间 21.9 个月后）仍在接受拉莫三嗪治疗。在其余 28.6%的患者中，停药的主要原因（平均 10.5 个月后）是缺乏疗效（19 例，15.2%）、癫痫发作频率增加（8 例，6.4%）和负性精神作用（5 例，4.0%）。基于意向治疗，应答率（癫痫发作频率减少 50%或更多）为 28.8%（局灶性癫痫为 35.6%，全面性癫痫为 26.7%，局灶性和全面性癫痫发作的癫痫为 22.4%）。所有癫痫发作类型的癫痫发作减少情况相似。拉莫三嗪与丙戊酸联合使用时更有效（p<0.005），与卡马西平或苯妥英联合使用时效果较差。逐步多元逻辑回归显示，丙戊酸（而不是拉莫三嗪剂量或浓度、合并用药、癫痫综合征或癫痫发作类型）是预测癫痫发作反应的唯一因素。28.0%的患者癫痫发作时间缩短且/或严重程度降低，8.8%的患者癫痫发作时间延长且/或严重程度增加。25.6%的患者出现阳性精神作用，8.0%的患者出现阴性精神作用（主要为攻击性）。总的来说，根据三种疗效标准，53.6%的患者受益，8.8%的患者恶化。最常见的剂量依赖性不良反应是共济失调、头晕和复视。
拉莫三嗪是一种对这一特殊患者群体有效且耐受性良好的药物，尤其是与丙戊酸联合使用时。
