Antiepileptic drug treatment in the nineties in The Netherlands.

In this review the state of the art of treating patients with epilepsy in the nineties in the Netherlands is presented. It describes general strategies for treatment with antiepileptic drugs and the history of development of the classical anticonvulsant drugs. Eight new drugs, including vigabatrin, lamotrigine, felbamate, oxcarbazepine, gabapentin, tiagabine, levetiracetam and topiramate are discussed. A review of their pharmacological and clinical properties is presented. Dutch experience with these drugs is included.     

Effect of carbamazepine, oxcarbazepine and lamotrigine on the increase in extracellular glutamate elicited by veratridine in rat cortex and striatum

Lamotrigine, carbamazepine and oxcarbazepine inhibit veratrine-induced neurotransmitter release from rat brain slices in concentrations corresponding to those reached in plasma or brain in experimental animals or humans after anticonvulsant doses, presumably due to their sodium channel blocking properties. Microdialysis measurements of extracellular glutamate and aspartate were carried out in conscious rats in order to investigate whether corresponding effects occur in vivo. Veratridine (10 M) was applied via the perfusion medium to the cortex and the corpus striatum in the presence of the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (1 mM in perfusion medium). Maximally effective anticonvulsant doses of carbamazepine (30 mg/kg), oxycarbazepine ( 60 mg/kg) and lamotrigine (15 mg/kg) were given orally.The uptake inhibitor increased extracellular glutamate and aspartate about 2-fold in striatum and about 7-fold and 3-fold, respectively, in cortex. Veratridine caused a further 2–3-fold increase in extracellular glutamate in striatum and cortex, respectively, but its effect on extracellular aspartate was less marked in both areas. None of the anticonvulsant compounds affected the veratridine-induced increases in extracellular glutamate or aspartate in the striatum which were, however, markedly inhibited by tetrodotoxin (1 M) and thus are sensitive to sodium channel blockade. In the cortex, the same drugs at the same doses did cause about 50% inhibition of the veratridine-induced increase in extracellular glutamate. Carbamazepine and to a lesser extent lamotrigine, but not oxcarbazepine, also inhibited the veratridine-induced increase in extracellular aspartate in the cortex.Although our results might seem to support the view that inhibition of glutamate and aspartate release is responsible for the anticonvulsant effects of lamotrigine, carbamazepine and oxcarbazepine, two complementary findings argue against this interpretation. First, as previously shown, inhibition of electrically induced release of glutamate requires 5 to 7 times higher concentrations of these compounds than release elicited by veratrine. Second, the present study indicates that doses totally suppressing convulsions caused no inhibition in the striatum and at best a 50% inhibition in the brain cortex. From this we conclude that the doses used here, although to some extent effective against veratridine, did not suppress the release of GLU and ASP elicited by the normal ongoing electrical activity of the glutamatergic and aspartatergic neurons and that the mechanism of the suppression of convulsions must be sought elsewhere.     

Effectiveness and Tolerability of Carbamazepine vs. Oxcarbazepine as Mood Stabilizers

Abstract

Background.?Patients with bipolar illness or maniac-type schizoaffective disorder often present a variety of symptoms and mixed responses to treatment. Several anticonvulsants have been found effective in the treatment of mood disorders. In the early 70's, the clinical efficacy of carbamazepine in the treatment of acute mania was reported. Oxcarbazepine has been available in the United States since 2000. Both drugs display a different spectrum of properties and side effect profiles. Objective.?To compare the effectiveness and tolerability of carbamazepine and oxcarbazepine in a naturalistic setting. Methods.?A retrospective and concurrent chart review of all patients treated with carbamazepine or oxcarbazepine (n = 33) as mood stabilizers between 01 and 12 2002. The effectiveness was evaluated using the Positive And Negative Syndrome Scale (PANSS). Tolerability was assessed according to side effects recorded on charts. Patients with charts that were not complete were excluded from this study. Results.?There were no significant differences in efficacy between groups on positive (F = 3.575, P = 0.075), negative (F = 2.641, P = 0.121), or the general subscales (F = 1.111, P = 0.306) of the PANSS. Patients in both groups developed gastrointestinal upset and headache, but no significant differences in tolerability between the two therapies were found (χ² = 0.466, df = 1, P = 0.659) and (χ² = 0.195, df = 1, P = 0.367 respectively). Conclusion.?In summary, the patient charts reviewed demonstrated that carbamazepine, as well as, oxcarbazepine are equally effective and tolerable as mood stabilizers.     

奥卡西平和左乙拉西坦治疗新诊断部分性发作癫疒间患儿的疗效分析

目的观察奥卡西平与左乙拉西坦对新诊断部分性发作癫疒间患儿的疗效和安全性。方法选择2011年1月至2013年12月新诊断部分性发作癫疒间患儿75例,随机分为2组。A组38例,给予奥卡西平治疗,剂量由10 mg/(kg·d)逐渐调整至最低有效量,最高为60 mg/(kg·d);B组37例,给予左乙拉西坦,剂量从5 mg/(kg·d)逐渐调整至最低有效量,最高为60 mg/(kg·d)。治疗12个月后,比较两组临床疗效、脑电图变化及不良反应。结果治疗后,A组的症状完全控制率(63.16%)、好转率(89.47%)与B组(安全控制率70.27%、好转率94.59%)比较差异无统计学意义(P>0.05);A组癫疒间样放电正常率(31.58%)、好转率(71.05%)与B组(37.84%、89.19%)比较差异无统计学意义(P>0.05);A组脑电背景α节律(9.67±1.36)与B组(9.84±1.31)比较差异无统计学意义(P>0.05);A组脑电图θ频段功率(30.64±7.66)比治疗前(20.67±6.36)明显增加(P<0.05),且高于B组(22.03±6.43),差异有统计学意义(P<0.05);A组不良反应发生率(20.05%)明显高于B组(2.70%),差异有统计学意义(P<0.05)。结论奥卡西平与左乙拉西坦治疗新诊断部分性发作癫疒间患儿均有效,但左乙拉西坦安全性更高。     

奥卡西平单药治疗2岁以下部分性发作癫痫患儿的临床观察

目的：探讨奥卡西平口服混悬液单药治疗2岁以下婴幼儿部分性发作癫痫的临床疗效和安全性。方法：收集2岁以下婴幼儿部分性发作癫痫患儿52例,给予奥卡西平口服混悬液单药治疗,起始量为8—10mg／（kg·d）,渐加量至20～40mg／（kg·d）,随访6～18个月,进行自身对照开放性研究,观察其疗效及安全性。结果：应用奥卡西平口服混悬液治疗后,有效率及控制率分别为94．2％、84．6％,8例（15．4％）患儿发生腹泻、呕吐、纳差、皮疹等不良反应。结论：奥卡西平口服混悬液治疗婴幼儿部分性发作癫痫疗效显著,临床应用方便,安全性好,不良反应较少,值得临床推广应用。     

左乙拉西坦和奥卡西平单药治疗新诊断儿童部分性癫痫的疗效及安全性分析

目的：观察左乙拉西坦（Levetiracetam,LEV）与奥卡西平（Oxcarbazepine,OXC）单药治疗新诊断部分性发作癫痫患儿的疗效和安全性。方法将68例新诊断部分性发作癫痫患儿随机分为两组,OXC组和LEV组各34例。观察两组的临床疗效、脑电图改变及不良反应。结果OXC组完成治疗32例,LEV组完成治疗34例。临床疗效比较OXC组总有效率为87．5％,LEV组总有效率为85．3％。两组总有效率比较差异无统计学意义（ P＞0．05）。脑电图改善情况比较OXC组有效率为50．0％,LEV组有效率为76．5％,LEV组有效率高于 OXC组,差异有统计学意义（P＜0．05）。 LEV组不良反应发生率低于OXC组,差异有统计学意义（P＜0．05）。结论奥卡西平与左乙拉西坦治疗儿童部分性发作癫痫临床疗效相当,但左乙拉西坦对脑电图改善优于奥卡西平,且不良反应少,安全性更高。     

天麻醒脑胶囊联合奥卡西平治疗原发性三叉神经痛的临床疗效

目的:观察天麻醒脑胶囊联合奥卡西平治疗原发性三叉神经痛的临床疗效.方法:采用前瞻性研究方法,按照随机数字表法对2016年7月-2019年2月我院86例原发性三叉神经痛患者进行分组,分为对照组和研究组,各43例,对照组患者服用奥卡西平,研究组患者在奥卡西平治疗基础上联合使用天麻醒脑胶囊辅助治疗.比较两组患者的临床疗效以及...     

拉莫三嗪与奥卡西平单药治疗成人新诊断局灶性癫痫的长期疗效及安全性比较

目的 比较拉莫三嗪(LTG)和奥卡西平(OXC)单药治疗成人新诊断局灶性癫痫的长期疗效、耐受性和安全性。方法 收集本院癫痫专病门诊新诊断的局灶性癫痫,随机分成OXC组和LTG组,根据临床情况调整剂量,OXC最大剂量1200 mg/d,LTG最大剂量300 mg/d,至少随访3年,评估二种药物单药治疗成人新诊断局灶性癫痫无发作率、保留率及不良反应。结果 2009年6月-2016年6月符合入组标准146例,其中OXC组74例,LTG组72例,2组1年无发作率分别为35.1%和51.3%(χ2=3.9,P=0.047),3年无发作率分别为21.6%和40.2%(χ2=5.96,P=0.015),LTG组总体无发作率高于OXC组(P<0.05); OXC组和LTG组1年保留率分别为59.5%和69.4%(χ2=1.59,P=0.208),3年保留率分别为44.6%和51.4%(χ2=0.68,P=0.411),LTG组总体保留率亦高于OXC组,但无明显差异(P>0.05)。OXC组和LTG组最常见的不良反应均为皮疹(6.8% vs. 8.3%)。结论 LTG单药治疗新诊断成人局灶性癫痫的长期无发作率高于OXC,两者不良反应较轻,有较好的安全性。     

奥卡西平单药及添加治疗部分性癫(癎)的疗效和安全性前瞻研究

目的:评估奥卡西平单药与添加治疗部分性癫患者的疗效、耐受性和安全性。方法:前瞻性对在同济医院癫诊疗中心就诊的67名部分性癫患者应用奥卡西平后进行临床随访观察,分为单药治疗组和添加治疗组,用药的前3个月及后3个月进行对比观察。结果:2组患者治疗前后发作频率减少的平均百分率有显著性差异(P=0.002)。单药治疗组与添加治疗组相比,前者用药前3个月发作完全控制的百分率、用药后3个月发作频率减少50%的百分率和发作完全控制的百分率(P=0.02,0.017,0.019)均明显低于后者。单药治疗组或添加治疗组自身用药的3个月及后3个月发作减少50%的百分率、发作减少75%的百分率、发作完全控制百分率均无明显差异(P>0.05)。治疗引起的不良反应发生率为19.40%(13/67),主要出现于用药的前3月。结论:奥卡西平是治疗部分性癫的一线药物,可用于新诊断或其他药物无法耐受和疗效不佳患者的单药或添加治疗。