抗癫痫药物临床治疗指南新看点课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,抗癫痫药物临床治疗指南新看点,制订临床指南的目的,应用指南是一种系统性阐述，用以帮助职业医师以及患者对于特定临床情况作出适当的医疗决定,NICE指南,目前仍缺乏高质量的临床试验支持新药单药治疗比传统药物更有效,研究中的药物副作用和耐受性并未提供足够多且一致的结果支持新药优于传统药物,仅9项比较新药和老药单药治疗新诊断癫痫患者生活质量的研究，未提供强有力的证据支持新药提高患者生活质量,传统抗癫痫药物单药治疗费用更便宜,Ref:National Institute for Health and Clinical Excellence.Technology appraisal,guidance 76:newer drugs for epilepsy in adults.Available at:,http:/www.nice.org.uk/TA076guidance.Accessed July 5,2005.,首选单药治疗药物应为传统抗癫痫药物如丙戊酸钠或卡马西平，除如下原因:,禁忌症,与患者目前服用的药物有潜在的相互作用,患者在既往治疗中对该药耐受性差,患者处于准备生育期,新型抗癫痫药物作为初始治疗的二线选择,Ref:National Institute for Health and Clinical Excellence.Technology appraisal,guidance 76:newer drugs for epilepsy in adults.Available at:,http:/www.nice.org.uk/TA076guidance.Accessed July 5,2005.,NICE指南,NICE缺点,1.评定的证据标准和证据分类没有明确的描述,2.传统抗癫痫药没有进行同样的评估,NICE指南,Neurology.2004,62(8):1252-1260,Neurology.2004,62(8):1261-1273,AAN指南,1.AAN指南有明确证据分类和证据评级,2.以有效性作为主要评估指标,3.缺点：,未评估传统药物,生活质量和成本效益未作为参考指标,抗癫痫临床治疗指南比较总结,评价指标,NICE指南,AAN指南,有效性,安全性,生活质量,成本效益,Payakachat et al.J Manag Care Pharma 2006,Payakachat et al.J Manag Care Pharma 2006,AEDs as Monotherapy,of Partial/Mix Generalized,Tonic-Clonic Seizure,ANN*,NICE,SIGN,Phenobarital,1st,-,-,Carbamazepine(generic Tegretol),Tegretol XR,1st,1st,1st,Phenytoin(generic Dilantin),1st,1st,-,Valproic acid(generic Depakene),Divalproex(Depakote),Divalproex(Depakote ER),1st,1st,1st,Primidone(generic Mysoline),-,-,-,Gabapentin(generic Neurontin),1st,-,-,Zonisamide)Zonegran),-,-,-,Tiagabine(Gabitril),-,-,-,Oxcarbazepine(Trileptal),1st,2nd,1st,Topiramate(Topamax),1st,2nd,-,Levetiracetam(Keppra),-,-,-,Lamotrigine(Lamictal),1st,2nd,1st,NICE指南和AAN指南对于新药的使用推荐,Lancet Neurol,2004;3:61821,DrugNewly diagnosed epilepsyRefractory epilepsy,PartialAbsencePartialPartialIdiopathicSymptomatie,mixedmonotherapygeneralisedgeneralised,USUKUSUKUSUKUSUKUSUKUSUK,Felbamate*NoNANoNAYes,NAYesNANoNAYes NA,GabapentinYesNoNoNoYesYesNoNoNoNoNoNo,LamotrigineYes,Yes,|Yes,Yes,|YesYes*YesYesNo Yes*YesYes*,LevetiracetamNoNoNoNoYesYesNoNoNoNoNoNo,OxcarbazepineYesYesNoNoYesYesYesYesNoNoNoNo,TiagabineNoNoNoNoYesYes|NoNoNoNoNoNo,TopiramateYesYes NoNoYesYes*YesYesYesYes*YesYes*,VigabatrinNANoNANoNAYesNANoNANoNAYes,ZonisamideNoNANo NAYes|NANoNANoNANoNA,None of the drugs is recommended as first choice in newly diagnosed epilepsy by the UK guidelines(see text).NA=not available.*Patients Unresponsive to standard drugs in Whom the risk/benefit ratio supports use;,only patients 18 years;,only patients 4 years with Lennox-Gastaut ayndrome;indication not approved FDA;only patients 6 years;|only patients 12 years;*only patients 2 years;only patients 16years;only generalized tonic-clonic seizures;in the UK the indications are limited to adjunctive use after failure of all other appropriate drug combinations;only West ayndrome;|only adulte.,新药的严重/非严重不良事件,Lancet Neurol 2004;3:61821,AEDSerious adverse vevntsNonserious adverse,FelbamateAplastic anaemia,hepatotoxicityGastrointestinal disturbancse,anorexia,insomnia,GabapentinAggresion*Weight gain,peripheral cedema,behavioural changes,LamotrigineRash,including Stevens Johnson and toxic epidermal necrolysisTics and insomnia,(high risk for children,also more common with concomitant,vaiproic-acid use and low with slow titration);hypereensitivity,reactions,including hepatic and renal failure,DIC,and arthritis,LevetiracetamNoneIrritability/behaviour change,OxcarbazepineHyponatraemia(more common in elderly people),rashNone,TiagabineNonconvulsive status epilepticusDizziness,asthenia,Topiramate Nephrolithiasis,open angle glaucoma,hypohidrosis,Metabolic acidosis,weight loss,depression,psychosislanguage dysfunxtion,paraesthesia,VigabatrinVisual field defects,psychosis,depressionWeight gain,ZonisamideRash,renal calculi,hypohidrosis Irritability,photosensitivity,weight loss,AED=antieptic drug;DIC=disseminated intravascular coagulation.*Mosthy in cognitively impaired patients;predominantly children.,上述各抗癫痫药治疗指南的差异在于单药治疗的推荐上（新药与传统药）,原因：1.证据的评估标准,2.制定指南的目的差异,临床医生在应用指南时特别注意,临床医生在应用指南时特别注意,要特别注意癫痫药物加重癫痫发作,可能加重某些癫痫综合征的抗痫药物,药物,综合症,可能加重的情况,卡马西平,失神癫痫,肌阵挛、失神发作,青少年肌阵挛癫痫,肌阵挛性发作,进行性肌阵挛癫痫,肌阵挛,中央回癫痫,CSWS.肌阵挛,苯巴英钠,失神癫痫,失神发作,进行性肌阵挛癫痫,小脑综合症，肌阵挛,苯巴比妥,失神癫痫,大剂量时失神发作,苯二氮卓类药物,LGS,强直性发作,氨已烯酸,失神癫痫,失神发作,伴肌阵挛的癫痫,肌阵挛,加巴喷丁,失神癫痫,失神发作,伴肌阵挛的癫痫,肌阵挛,拉莫三嗪,严重的肌阵挛癫痫,大剂量时 GTCS,青少年肌阵挛癫痫,肌阵挛性发作,Ref:Epilepsia.39(Suppl.3):S15-S18,1998,Topiramate Vigabatrin,0,2,4,6,8,10,Clonazepam,Clobazam,Sodium Valproate(,德巴金,),Carbamazepine,Barbexaclone,Primidone,Phenobarbital,Ethosuximide,Sulthiame,Oxcarbazepine,Phenytoin,Lamotrigine,Gabapentin,Elger,等对,1006,例局灶性癫痫,（包括单药和添加治疗）荟萃分析,抗癫痫药物恶化发作,癫痫患者发作增加的百分比,临床医生在应用指南时特别注意,治疗要个体化,要特别关注特殊人群:儿童、妇女、老人,临床医生在应用指南时特别注意,认识的更新,SANAD试验,发现丙戊酸和其它新抗癫痫药在癫痫治疗的综合作用中明显优于其它药物,研究,A:,基线的人口学资料和临床表现,CBZ,(n=378),GBP,(n=377),LTG,(n=378),OXC,(n=210),TPM,(n=378),Total,(n=1721),性别,n(%),男,女,208(55),170(45),207(55),170(45),208(55),170(45),1