妥泰治疗癫痫临床疗效观察

目的：探讨妥泰对各种类型癫痫的疗效及副作用。方法：将32例各种类型的癫痫患者随机分为治疗组、对照组进行疗效对比。结果：治疗组总有效率73．3％,对照组总有效率47．1％,P＜0．01,两组疗效有显著性差异。副反应的发生率治疗组占33．3％,对照组占52．9％,P＜0．05,两组之间亦有显著性差异。结论：妥泰对各种类型的癫痫不仅疗效显著而且出现的副反应相对较少。     

妥泰联合中药治疗小儿继发性癫痫的临床疗效

目的研究和观察妥泰联合中药治疗小儿继发性癫痫的治疗效果。方法回顾总结妥泰联合中药治疗小儿继发性癫痫病例,观察妥泰加中药治疗效果。结果 62例小儿继发性癫痫中,治疗组远期有效26例,对照组13例,两组差异显著,两组治疗效果无效差异也很明显,两组有效差异不明显。结论妥泰联合中药治疗小儿癫痫疗效好,副作用小,耐受性好,可推广应用。     

妥泰对宫内缺血Wistar大鼠海马星形胶质细胞及学习记忆能力的影响

目的 观察妥泰对宫内急性脑缺血损伤的Wistar大鼠海马星形胶质细胞及学习记忆能力的影响。方法 夹闭足月妊娠大鼠子宫血管,制成急性脑缺血损伤的新生鼠模型,治疗组给予妥泰,观察脑缺血后再灌注3h、6h、24h、3d、7d、14d、21d、28d海马GFAP标记的星形胶质细胞的变化,生后28d通过Morris全自动水迷宫实验,比较各组新生鼠学习记忆能力的差别。结果 妥泰治疗组新生鼠反应性星形胶质细胞在脑缺血再灌注早期的增生程度以及继之发生的大量减少的程度均较缺血对照组明显降低（P〈0．05）,多次给药组可以减少其晚期的过度增生（P〈0．05）,妥泰治疗组新生鼠学习记忆能力明显好于缺血对照组（P〈0．05）,且多次给药组学习记忆能力好于单次给药组（P〈0．05）。结论 妥泰可以明显减少宫内急性脑缺血后新牛大鼠星形胶质细胞的异常变化,改善急性脑缺血损伤的Wistar大鼠生后的学习记忆能力。     

Topiramate moderately reduces the motivation to consume alcohol and has a marked antidepressant effect in rats

Background: In recent human studies, the anticonvulsant drug topiramate (TPM) has shown efficacy in treating alcohol craving and mood disorders. However, preclinical evidence supporting such effects is surprisingly sparse. Three experiments were conducted here to assess possible anticraving and antidepressant effects of TPM using animal models. Methods: In Experiment 1, rats were given 23 weeks ad libitum access to food, water, and either beer (4.44% ethanol v/v) or “near‐beer” (a calorie‐matched nonalcoholic beer, 0.44% ethanol) in their home cages. They were then restricted to daily 1 hour operant sessions in which they licked for water and either beer or near‐beer under a progressive ratio schedule of reinforcement in a lickometer apparatus. The acute effects of TPM on the motivation to consume beer or near‐beer were then assessed. The effects of naloxone were also assessed (as a positive control) after TPM testing. In Experiment 2, rats were given 11 weeks of ad libitum home‐cage access to food, water, and beer. They then received repeated daily injections of TPM and effects on beer consumption under ad libitum home cage access conditions were monitored. In Experiment 3, the effects of TPM were assessed in the modified Porsolt forced swim test, emergence test, and elevated plus‐maze (EPM) using alcohol naïve rats. Results: Topiramate (10, 20, and 40 mg/kg) significantly reduced the motivation to lick for beer, although the maximal effect was moderate in comparison with naloxone (10 mg/kg). However, naloxone, unlike TPM, also reduced responding for near‐beer suggesting an alcohol‐specific effect of TPM. In Experiment 2, TPM (40 and 80 mg/kg) tended to transiently reduce alcohol consumption in the home cage under ad libitum access but this effect disappeared with repeated administration of the drug. TPM (10 to 80 mg/kg, given twice over 4 hours before test) produced a robust dose‐dependent decrease in immobility and increase in active coping strategies in the forced swim test similar to that seen with desipramine (2 × 20 mg/kg). There were modest anxiolytic effects of TPM on the EPM and emergence tests. Conclusions: With acute administration, TPM is moderately effective and relatively selective in reducing the drive to consume alcohol in Wistar rats. This anti‐alcohol effect is modest in comparison with naloxone and appears to dissipate under conditions of chronic treatment and ad libitum alcohol access. A marked antidepressant‐like effect in the forced swim test and partial anxiolytic effects in other animal models suggests that TPM may be a beneficial treatment for affective disorders. These preliminary results suggest further research is warranted to resolve the mechanisms involved in TPM modulation of both mood and alcohol consumption.     

托吡酯快速加量法治疗小儿癫痫临床观察

目的　观察托吡酯快速加量法治疗小儿癫痫时的疗效及不良反应。方法　对 30例符合1981年国际抗癫痫联盟的癫痫临床发作的分类与 1989年癫痫与癫痫综合征分类中的各型癫痫患儿在住院期间应用快速加量法给予托吡酯进行治疗。治疗剂量由小剂量开始 ,平均 1.0mg (kg·天 ) ,每2～ 3天增加 1.0mg kg ,平均 13天达目标剂量 [平均 4 .5mg (kg·天 ) ]至发作控制 ,同时观察疗效及副作用。结果　 (1)托吡酯快速加量法治疗住院小儿癫痫 30例平均加药时间 13天达平均剂量 4 .5mg (kg·天 ) ,其总疗效为发作完全控制 14例 (4 6 .7% ) ,发作减少≥ 75 % 9例 (30 % ) ,发作减少≥ 5 0 % 5例 (6 .7% )。(2 )发生不良反应总例数 8例 (2 6 .7% )。表现为食欲降低 5例 (16 .7% ) ;低热为 3例 (10 % ) ;嗜睡、困倦 2例 (6 .7% ) ;多动、兴奋 2例 (6 .7% ) ;部分有交叉。结论　应用托吡酯治疗住院的癫痫儿童时可以快速加量 ,可以很快达到有效控制 ,安全、不良反应小     

托吡酯联合丙戊酸钠对难治性癫痫的疗效和安全性研究

目的：评价托吡酯联合丙戊酸钠治疗难治性癫痫的疗效及安全性。方法选取2010年5月~2013年4月我院收治的难治性癫痫患者110例,随机分为观察组和对照组,其中观察组55例,采用托吡酯联合丙戊酸钠治疗,对照组55例,采用单用托吡酯治疗,比较两组患者的临床疗效、脑电图变化及不良反应发生率。结果观察组总有效49例,总有效率为89.09%,对照组总有效41例,总有效率为74.55%,两组患者总有效率比较差异有统计学意义（P〈0.05）,此外观察组显效率及无效率与对照组比较差异均有统计学意义（χ2=3.9111,P〈0.05）;两组患者治疗过程中7例患者发生不良反应,发生率为6.36%,包括头晕、头痛、疲倦、食欲减退及恶心呕吐等,随着治疗的延长,不良反应逐渐缓解,未见皮疹及肝肾等重要脏器损害等严重不良反应发生,两组患者不良反应发生率比较差异无统计学意义。结论托吡酯联合丙戊酸钠治疗难治性癫痫疗效好,值得在临床上予以推广。     

妥泰添加及药物转换治疗儿童癫痫94例疗效观察

目的　观察妥泰 ( TPM)添加治疗儿童癫痫的疗效及癫痫发作完全控制后转换为 TPM单药治疗的可行性。方法　对 94例应用一线抗癫痫药控制不满意的患儿 ,其中部分性发作 ( PS) 5 2例 ,全身性发作 ( GS) 4 2例 ,在原用抗癫痫药 ( AEDs)的基础上加用 TPM 0 .5～ 1.0 mg/ kg.d,日 2次 ,口服 ,每 5～ 7d加量一次 ,直至达到目标剂量。治疗 12周后根据发作频率将疗效分为完全控制、显效、有效和无效。对发作完全控制后的癫痫患儿 8～ 12周后 ,逐渐减去其它抗癫痫药 ,转换为 TPM单药治疗。结果　 5 2例 PS患儿应用 TPM治疗后得到完全控制 2 9例 ,显效 10例 ,有效 6例 ,无效 7例 ,总有效率为 86 .5 %;42例 GS患儿治疗后完全控制 16例 ,显效 9例 ,有效 8例 ,无效9例 ,总有效率为 78.6 %;在完全控制发作的 2 9例 PS中 ,及 GS的 16例中 ,转换为单用 TPM治疗达 2个月以上尚未见发作的分别为 7例、4例。94例加用 TPM后 2 9例出现的不良反应 ,占 30 .9%,其中以食欲减退多见 ,其次为困倦及体重下降等 ,在加量期过后大多消失 ,治疗前后血、尿常规、肝、肾功能未发现有临床意义的改变。结论　 TPM是一种广谱、高效、安全的 AEDs,适用于小儿各型癫痫的联合和单药治疗。     

Side Effects of Antiepileptics— A Review

Abstract:   Older generation antiepileptic drugs like Phenobarbital (Luminal), carbamazepine (Tegretol), phenytoin (Dilantin), and valproic acid (Depakote) have several shortcomings such as suboptimal response rates, significant adverse effects, several drug interactions, and a narrow therapeutic index. New antiepileptic drugs have been developed in the last decade to overcome some of these problems. These newer generation antiepileptics like felbamate (Felbatol), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), tiagabine (Gabitril), topiramate (Topamax), and zonisamide (Zonegran) have better tolerability profiles, low interaction potential, and significantly less enzyme inducing or inhibiting properties. As the use of antiepileptic drugs has expanded to include treatment of neuropathic pain, newer side effects have been reported. In addition to the common side effects of antiepileptic drugs, like dizziness, drowsiness, and mental slowing; other side effects like weight gain, metabolic acidosis, nephrolithiasis, angle closure glaucoma, skin rash, hepatotoxicity, colitis, and movement and behavioral disorders, to name a few, have been brought to our attention. This review is an attempt to highlight the features and incidences of some of these side effects.     

First trimester exposure to topiramate and the risk of oral clefts in the offspring: A systematic review and meta-analysis

Topiramate (TPM) is an increasingly used drug during childbearing ages for treatment of epilepsy, migraine, and appetite suppression as well as for off-label indications such as sleep and psychiatric disorders. Presently, while some reports suggested an increased risk of oral cleft (OC), these reports are balanced by studies that could not confirm such association. We conducted a meta-analysis of all studies reporting on women exposed to TPM during pregnancy. Of the 2327 publications reviewed, 6 articles met the inclusion criteria including 3420 patients and 1,204,981 controls. The odd ratio (OR) of OC after the first trimester exposure to TPM exposure was 6.26 (95% confidence interval: 3.13–12.51; P = 0.00001). This study provides strong evidence that TPM is associated with an increased risk of OC in infants exposed to TPM during embryogenesis and should lead to a careful review of TPM use in women of reproductive ages.     

托吡酯对亚胺基二丙腈诱发大鼠行为改变及多巴转运体的影响

目的 利用亚胺基二丙腈（IDPN）诱发大鼠行为改变,制作抽动症模型,观察托吡酯（TPM）治疗的疗效.方法 将24只35d日龄的大鼠随机分为A、B、C 3组,每组8只.A、B组大鼠予以腹腔注射IDPN 1周,然后A组予以TPM灌胃治疗 B、C组大鼠予以相应量的0.9%氯化钠注射液（NS）灌胃,在观察大鼠头面部刻板样运动评分后,取大鼠脑组织,固定、切片,进行免疫组化染色,测定各组大鼠基底节区多巴胺转运体（DAT）的光密度水平.结果 腹腔注射IDPN后,A、B组头面部刻板样运动评分较注射前明显升高（P＜0.05） A、B组大鼠基底节区DAT免疫组化COD值较C组增加（P＜0.01） 在给予TPM灌胃治疗后,大鼠头面部刻板样运动评分明显改善（P＜0.05）,A组大鼠基底节区DAT免疫组化COD值较B组明显下降（P＜0.01）.结论 托吡酯能够改善IDPN诱发的大鼠行为改变.