左乙拉西坦单药治疗80例成人癫癎的疗效及安全性

目的：评价左乙拉西坦单药治疗各种类型成人癫癎的疗效和安全性.方法：80例各类型新诊断的成人癫癎患者,口服左乙拉西坦治疗,随访1年,观察治疗后患者癫癎发作次数变化及不良反应发生率.结果：左乙拉西坦单药治疗成人癫癎的总有效率为75.0%;对部分性发作可能更为有效,有效率为77.08 %;不良反应发生率为16.3%.因疗效不佳退出为18.75%.结论：在单药治疗成人癫癎中,左乙拉西坦是一种安全有效的抗癫药物,且对部分性和全面性癫癎发作均有效.     

影响新诊断癫(癎)患者初次药物治疗效果的因素

目的 探讨影响新诊断癫(癎)患者初次药物治疗效果的因素.方法 对155例年龄4～68岁新诊断的癫(癎)患者给予单药治疗,至少观察1年,以稳定期初次发作时间和早期治疗失败时间为终点事件,其中治疗失败的原因包括发作控制不佳和/或不能耐受药物不良反应.采用Cox回归分析判断癫(癎)患者临床特点及实验室检查结果对药物治疗效果的影响.结果 多因素Cox回归分析显示:癫(癎)家族史(HR=2.39,P<0.05)、EEG癫(癎)波(HR=2.05,P<0.005)、治疗前发作次数(HR=1.76,P<0.05)是影响稳定期初次发作时间的因素;女性患者(HR=4.25,P<0.001)、部分性发作(HR=2.54,P<0.05)、EEG癫(癎)波(HR=3.11,P<0.005)是影响早期治疗失败时间的因素.结论 EEG癫(癎)波、癫(癎)家族史、治疗前发作次数、发作类型(部分性发作)、女性患者是影响新诊断癫(癎)患者初次药物治疗效果的因素.     

加巴喷丁治疗癫(癎)32例疗效观察

目的观察加巴喷丁抗癫癎作用的有效性与安全性。方法观察各种类型癫癎患者32例,以GBP用药前3个月平均发作频率为基线,与用药3个月后发作频率进行比较,观察疗效及不良反应。结果加巴喷丁对全面性发作治疗疗效优于部分性发作,新诊断癫癎有效率高于难治性癫癎。加巴喷丁不良事件发生率低且症状轻微。结论加巴喷丁对各种类型癫癎发作均有一定疗效,是一种安全性较好的药物。对全身性发作类型有效,对部分性发作疗效欠佳,对新诊断癫癎有效,难治性癫癎疗效欠佳。     

拉莫三嗪治疗癫癎的有效性与剂量、血药浓度及合并用药关系的研究

目的探讨拉莫三嗪(LTG)单药及不同配方治疗癫癎的有效性及与血药浓度等相关因素的关系。方法 126例患者分4组:拉莫三嗪单药治疗组(LTG)42例;服丙戊酸(VPA)以拉莫三嗪为添加治疗的LTG+VPA 组35例;服丙戊酸和卡马西平(CBZ)添加拉莫三嗪组(LTG+VPA+CBZ)33例;服卡马西平添加拉莫三嗪(LTG+ CBZ)组16例。拉莫三嗪按常规逐渐加量,在达到目标剂量后一个月及有效维持量时采血,高效液相色谱法测拉莫三嗪、丙戊酸及卡马西平血药浓度。结果拉莫三嗪单药或合并用药时疗效无明显差异,总有效率为81．8％,对全面性发作效果较佳,有效率90．6％,尤其是失神发作;对部分性发作有效率75．0％,两者有显著性差异。89％的有效患者拉莫三嗪血药浓度在1-8μg/mL范围内,且此范围内疗效与血药浓度呈正相关。血药浓度>8μg/mL时不良反应发生率增加有显著性。本组患者中无皮疹发生,可能与研究中起始剂量低、加量慢有关。结论拉莫三嗪单药及不同配方情况下对癫癎全面性发作效果更好。其有效血药浓度范围较大,且与疗效和副作用相关。     

左乙拉西坦单药治疗各型癫癎的疗效和安全性临床观察

目的对50例单独应用左乙拉西坦（LEV）的癫癎患者进行临床观察和随访,以评估左乙拉西坦治疗各型癫癎的疗效和安全性。方法采用开放性自身对照方法对2009年6月~2010年3月本院及其门诊就诊的50例左乙拉西坦单药治疗的癫癎患者进行随访研究,收集治疗前后患者发作频率变化、发作情况、不良反应以及退出原因。其随访均在半年以上。结果 LEV单药治疗后癫癎发作完全控制率48%,有效率38%;其中部分性发作完全控制率40.9%,有效率45.5%;全面性发作完全控制率53.6%,有效率32.1%,对west综合症亦有效。不良反应包括情绪异常、易激惹12%（6/50）,头晕8%（4/50）,白细胞减少2%（1/50）;上述不良反应均为一过性,在2~5周内自然消失,未导致停药,未发现过敏以及肝、肾功能异常等严重不良反应。结论 LEV是一种安全有效的抗癫癎药物,对部分性和全面性发作均有效,且安全耐受性较好。     

左乙拉西坦单药治疗脑梗死后迟发性癫癎的临床观察

目的:观察左乙拉西坦对老年脑梗死后迟发性癫癎的疗效和安全性。方法:左乙拉西坦单药治疗新诊断的老年脑梗死后迟发性癫癎18例,起始剂量250mg,每日2次。根据疗效调整剂量,每日最大量不超过3000mg。观察癫癎发作的频率、类型及不良反应。结果:18例迟发性癫患者应用左乙拉西坦500～1500mg·d-1后有16例(88.9%)未再有癫癎发作。3例(16.7%)有嗜睡,2例(11.1%)有头昏表现,不良反应总发生率为27.8%(5/18例)。上述不良反应均未经特殊处理,在l～2个月自行消失,无一例因不良反应退出治疗。结论:左乙拉西坦是治疗老年缺血性脑卒中后迟发性癫安全、有效,而且耐受性良好的药物。     

奥卡西平与卡马西平单药治疗儿童部分性癫(癎)的对照研究

目的 比较奥卡西平与卡马西平单药治疗儿童部分性癫(癎)的疗效.方法 71例新诊断的儿童部分性癫(癎)患者按单双号顺序分为奥卡西平组(35例)和卡马西平组(36例),并给予相应的药物治疗;6个月后进行疗效评价,观察不良反应.结果 奥卡西平组和卡马西平组分别有25例及29例完成6个月治疗;脑电图改善率分别为44.0%及44.8%;显效率分别为92.0%及86.2%;不良反应发生率分别为22.2%及41.2%,两组间比较差异无统计学意义(均P>0.05);卡马西平组2例出现严重不良反应.结论 奥卡西平与卡马西平单药治疗新诊断的儿童部分性癫(癎)均有很好的疗效,不良反应及耐受性相似,但奥卡西平组未见严重的不良反应.     

拉莫三嗪治疗成人部分性发作癫癎的临床疗效与安全性研究

目的评价拉莫三嗪治疗成人部分性发作癫癎的临床疗效与安全性。方法收集成人部分性发作癫癎患者89（76）例,分别给予拉莫三嗪单药、替换或添加治疗,进行开放性自身对照研究,随访24周发作情况,登记监测不良反应。结果 89例中76例完成终点试验,总有效率为82.8%,平均起效剂量为（99.7±18.6）mg/d,平均起效时间为（17.8±5.4）d,保留率为85.39%。不良反应发生率为15.8%,皮疹发生率为2.2%。结论拉莫三嗪是一种安全、有效的抗癫癎药物。     

托吡酯单药治疗癫癎的临床观察

目的观察托吡酯(TPM)单药治疗癫癎的临床疗效和不良反应.方法应用TPM治疗64例癫癎患者,平均日剂量为138 mg,服药6～36个月,将每例患者治疗最后3个月的发作次数与基础期比较,并观察记录其不良反应.结果本组总有效率为78.1%,其中控制率为42.2%.不良反应的发生率为70.3%,中枢神经系统的不良反应占57.1%,多数较轻微且持续时间较短.10例(15.6%)因治疗无效、不良反应或经济等原因终止治疗.结论 TPM长期单药治疗癫癎疗效明显,耐受性好,较为安全.     

托吡酯单药治疗各型癫癎的临床研究

目的观察托吡酯单药治疗成人和儿童各型癫癎的临床效果与安全性.方法用开放性试验的方法对34例癫癎患者进行了添加转单药以及首诊单药的托吡酯治疗;以加用托吡酯前3个月的月均发作频率为基准,与单用或转换单用托吡酯进入稳定期后3个月的月均发作频率进行比较,按常规计算发作减少百分比的中位值和有效率百分比.结果托吡酯无论在添加转单药还是单药的治疗上均有明显疗效,且抗谱广,可用于单纯部分性发作有或全面性发作、复杂部分性发作有或全面性发作、婴儿痉挛症,无耐药现象.14岁以上者托吡酯单药治疗的剂量明显低于添加治疗组.托吡酯的副反应以中枢神经系统最常见,但导致治疗中断的副反应尚未见到.结论托吡酯是一个广谱抗癫癎药,疗效肯定,无耐药性,无严重副反应,可用于单药治疗.     

Lamotrigine in typical absence epilepsy.

Lamotrigine (LTG) is an anti-epileptic drug effective in partial seizures and generalized epilepsy. There is growing evidence of the usefulness of LTG in childhood (CAE) orjuvenile (JAE) absences resistant to previous treatment. In this study all patients were identified using strict diagnostic criteria and subdivided into two groups. (1) Eight patients affected by absence seizures resistant to valproic acid or ethosuximide, received LTG as an-add-on therapy, (2) seven patients affected by typical absence seizures not previously treated, received LTG monotherapy after the diagnosis. In the patients with resistant absence seizures, a full control of seizures was obtained. In five of them, after a mean period of 12.5 months, the previous anti-epileptic drugs were withdrawn leaving the patients on LTG monotherapy. In one patient, absences relapsed and valproic acid was therefore added again to LTG to regain control of the seizures. In six of the seven patients on LTG monotherapy after the diagnosis, a full control of seizures was obtained. In the seventh patient the drug was stopped due to a skin rash. In conclusion LTG appears to be effective in resistant absence seizures in combination with valproic acid. Moreover, our preliminary data suggest that lamotrigine might be used as monotherapy in typical absence seizures. The advantages and disadvantages of LTG monotherapy in this type of epilepsy are discussed.     

Lamotrigine versus vigabatrin as an add-on therapy in refractory epilepsy: prospective study

Lamotrigine (LTG) and Vigabatrin (VGB) has been licensed widely as adjunctive therapy for partial and secondary generalized seizures. We compared the efficiency of Lamotrigine and Vigabatrin as adjuvant therapy for 33 patients (16 male and 17 female) with drug-resistant partial epileptic seizures (simple and complex) with secondary generalization receiving combination therapy (carbamazepine--CBZ and valproic acid--VPA). Patients were enrolled if they had experienced two partial seizures (simple or complex) and one secondary generalization/month, despite combination therapy. Neurologic evaluation including CT, MRI and EEG was performed every 3 months during observation. Blood specimens for CBZ and VPA plasma concentration were obtained prior to the first LTG or VGB dose and twice a year during the treatment. The assessment of LTG and VGB effectiveness was performed in 2-month intervals during 2-3 years for vigabatrin (mean daily dose 2.0 g) and 1-2 years for Lamotrigine (mean daily dose 0.3 g). The treatment (CBZ, VPA or both) with Vigabatrin or Lamotrigine as adjunctive therapy was effective in about a half of patients with refractory epilepsy. Findings suggest that the reduction in partial seizures (simple or complex) frequency with Vigabatrin is greater than that with Lamotrigine. On the other hand, Lamotrigine seems to be more effective in patients with partial epileptic seizures with secondary generalization.     

Lamotrigine: A Review of Antiepileptic Efficacy

Summary: Lamotrigine (LTG) is a chemically novel anti-epileptic drug (AED) that blocks voltage-sensitive sodium channels, leading to inhibition of neurotransmitter release, principally glutamate. LTG is active in a wide range of pharmacologic models of epilepsy, demonstrating a potency and duration of action generally superior to currently available AEDs. Preliminary evidence of efficacy was provided by single-dose studies showing effects on reducing interictal spike activity and photoconvulsive response. A total of eight randomized, double-blind, placebo-controlled, crossover trials have established the efficacy of LTG in patients with refractory partial epilepsy. Literature reports suggest LTG also is effective in patients with idiopathic generalized epilepsy, including absence seizures, and in patients with Lennox-Gastaut syndrome. Other reports suggest that LTG is useful in the pediatric population, and an interim report of an open monotherapy trial suggests that the efficacy of LTG was comparable to that of carbamazepine (CBZ) but the adverse experiences leading to discontinuation were less frequent.     

Lamotrigine Monotherapy in Newly Diagnosed Untreated Epilepsy: A Double-Blind Comparison with Phenytoin

PURPOSE: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared. METHODS: In a double-blind parallel-groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for < or =48 weeks. RESULTS: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme-inducing drug, whereas those taking LTG did not. CONCLUSIONS: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.     

A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group

OBJECTIVE: To compare the safety and efficacy of add-on lamotrigine and placebo in the treatment of children and adolescents with partial seizures. BACKGROUND: Add-on and monotherapy lamotrigine is safe and effective in adults with partial seizures, and reports of preliminary uncontrolled trials suggest similar benefits in children. METHODS: We studied 201 children with diagnoses of partial seizures of any subtype currently receiving stable conventional regimens of antiepileptic therapy at 40 study sites in the United States and France. After a baseline observation period (to confirm that more than four seizures occurred in each of two consecutive 4-week periods), patients were randomized to add-on lamotrigine or placebo therapy. A 6-week dose-escalation period was followed by a 12-week maintenance period. RESULTS: Compared with placebo, lamotrigine significantly reduced the frequency of all partial seizures and the frequency of secondarily generalized partial seizures in these treatment-resistant patients. The most commonly reported adverse events in the lamotrigine-treated patients were vomiting, somnolence, and infection; the frequency of these and other adverse events was similar to that in the placebo-treated group, with the exception of ataxia, dizziness, tremor, and nausea, which were more frequent in the lamotrigine-treated group. The frequency of withdrawals for adverse events was similar between groups. Two patients were hospitalized for skin rash, which resolved after discontinuation of lamotrigine therapy. CONCLUSIONS: Lamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile.     

The use of lamotrigine, vigabatrin and gabapentin as add-on therapy in intractable epilepsy of childhood.

PURPOSE: Lamotrigine (LTG), vigabatrin (VGB) and gabapentin (GBP) are three anti-epileptic drugs (AEDs) used in the treatment of children with epilepsy for which long-term retention rates are not currently well known. This study examines the efficacy, long-term survival and adverse event profile of these three agents used as add-on therapy in children with refractory epilepsy over a 10-year period. METHODS: Three separate audits were conducted between February 1996 and September 2000. All children studied had epilepsy refractory to other AEDs. Efficacy was confirmed if a patient became seizure free or achieved >50% reduction in seizure frequency for 6 months or more after starting therapy. Adverse events and patient survival for each drug were recorded at the end of the study period. RESULTS: Between September 1990 and February 1996, 132 children received LTG, 80 VGB and 39 GBP. At the 10-year follow-up audit, 33% of the children on LTG had a sustained beneficial effect on their seizure frequency in contrast to 19% for VGB and 15% for GBP. No significant difference in efficacy was found in children with partial seizures. Children with epileptic encephalopathy (EE) including myoclonic-astatic epilepsy and Lennox-Gastaut Syndrome (LGS) achieved a more favorable response to LTG. The main reasons for drug withdrawal were lack of efficacy for VGB, apparent worsening of seizures for GBP and the development of a rash for LTG. CONCLUSIONS: Lamotrigine is a useful add-on therapy in treating children with epilepsy. It has a low adverse event profile and a sustained beneficial effect in children with intractable epilepsy.     

Lamotrigine and Seizure Aggravation in Severe Myoclonic Epilepsy

Summary: Purpose: In severe myoclonic epilepsy of infancy (SME), multiple drug-resistant focal and generalized seizure types occur. Lamotrigine (LTG), found effective in many generalized and partial seizures, has been little used in severe childhood epilepsy syndromes with multiple seizure types. We studied the effects of LTG in SME.
Methods: Twenty-one patients with SME, aged 2–18 years, were treated with LTG, 20 in add-on and one in monotherapy. LTG was started at 0.2–2.5 mg/kg/day and increased to 2.5–12.5 mg/kg/day. For each seizure type, excluding atypical absences, >50% variations compared with the 2 months preceding LTG were considered indicators of response, also taking into account the degree of disability each seizure type produced.
Results: LTG induced worsening in 17 (80%) patients, no change in three, and improvement in one. There was >50% increase in convulsive seizures in eight (40%) of 20 patients. Myoclonic seizures worsened in six (33%) of 18 patients. Of five patients improving in at least one seizure type, four had concomitant worsening of more invalidating seizures. Clear-cut worsening appeared within 3 months in most patients but was insidious in some. LTG was suspended in 19 patients after 15 days-5 years (mean, 14 months) with consequent improvement in 18.
Conclusions: The pronounced seizure deterioration during LTG treatment was not attributable to the natural course of the disease and could be a direct effect of therapeutic LTG doses. LTG treatment seems inappropriate in SME.     

Verträglichkeit von Lamotrigin – eine Literaturübersicht

Lamotrigine (LTG) was licensed in Germany in 1993 for the treatment of patients with focal and secondary generalized epileptic seizures. Currently, the indication has been extended to also include several generalized epilepsy syndromes. For patients from 2–11 years of age, Lamotrigine may be used in add-on therapy, but also in monotherapy.The worldwide use has reached a figure of several million patients. The most important side effects are skin reactions, which mostly consist of morbiliform rashes without systemic reactions. However, in rare occasions severe complications such as toxic epidermal necrolysis or Stevens-Johnson syndrome may occur. The probability of such severe reactions is markedly reduced if small initial dosages and slow titration routes are chosen. This strategy is therefore almost mandatory and particularly true for the combination with valproic acid. If the cautious titration regimen is used, the risk of skin reactions is in the range of other standard AEDs, such as carbamazepine or even slightly lower. According to the clinical studies, the incidence of rash is somewhat higher in children. This may partially result from the higher rate of combinations of LTG with valproic acid in this patient group.¶???The CNS side effect profile is favorable. Under monotherapy conditions, vertigo, diplopia or ataxia are less frequent than under comparable dosages of carbamazepine or phenytoin. The highest incidence of neurotoxic effects is reported for the combination with high-dose carbamazepine, the reduction of which should therefore be considered if LTG is initiated. Insomnia may be a lamotrigine-specific adverse effect just as aggravated behavior disturbances of mentally retarded patients. On the other hand, LTG frequently shows favorable effects on cognition and is less sedating as other AEDs. Due to its excellent tolerability, LTG has also become an important treatment option for elderly patients and for female patients as well because of its lack of systemic hormonal effects. In summary, LTG is an AED with a favorable tolerability profile.     

Gabapentin and lamotrigine in Indian patients of partial epilepsy refractory to carbamazepine

52 patients (25 males and 27 females) suffering from refrectory partial seizures, of not more than two years duration and on carbamazepine monotherapy were enrolled in this study. Patients were randomly put on gabapentin (19 males and 8 females) or lamotrigine (6 males and 19 females) as add on therapy. The efficacy of the drugs was assessed by the seizure frequency, pattern of seizures and seizure free interval. The safety was evaluated from the biochemical investigations and the adverse effects observed or reported by the patients during the course of the study. The average frequency of basal partial seizures was 6.26+3.86 and 5.04+2.47 which decreased significantly (p<. 001) after 12 weeks of add on therapy to 1.75+2.16. and 1.68+2.94 in the GBP and LTG group respectively. However, there was no significant difference between the two drugs after 12 weeks of add on therapy. The PCB (primary change in basal seizure frequency) values decreased to -72+34.92 and -76.22+29.68 in the GBP and LTG group respectively. The difference in these two groups was not significant. The responder rate was 77.7% and 92% respectively in GBP and LTG group respectively. GBP was found to be more effective in partial seizures with secondarily generalization while LTG was effective in all subtypes of partial seizures. The abnormal scalp EEG was recorded in 33.3% (9 of 27 patients) in GBP group and 40 %( 10 of 25 patients) in LTG group and it did not revert to normal in 33.3% and 40% of patients in either of groups (GBP/LTG). Minor side effects which were self limiting were noticed in 80% in groups I and 74% were groups II.