癫痫病制订临床指南的目的课件

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400-0196-638广州协佳癫痫医院临床指南的存在问题1.评估标准不统一2.缺乏证据≠不存在的证据3.时间局限性→过时、更新4.受到药厂的影响，有一定的利益因素5.由少部分专家制定6.个体差异7.临床医生执行时困难ShorvonS.Epilepsia2006,4).1091~3制订指南原则透明：无利益驱动公平：所有数据采用同样的评估标准严格：评价方法严格可行动态：不断更新NICE指南对于抗癫痫药物使用的指证，药物选择，换药，停药等原则性问题均作出了相应推荐Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.NICE指南NICE在治疗中①尽可能选择单药治疗②不推荐常规监测看癫痫药物的血药浓度③停药原则Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.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:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.400-0059-826昆明军海脑科医院NICE指南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:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.Neurology.2004,62(8):1252-1260Neurology.2004,62(8):1261-1273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×Payakachatetal.JManagCarePharma2006400-0120-772沈阳万佳癫痫医院NICE指南和AAN指南对于新药的使用推荐LancetNeurol2004;3:618–21Drug Newlydiagnosedepilepsy Refractoryepilepsy Partial Absence Partial Partial Idiopathic Symptomatie mixed monotherapy generalised generalised US UK US UK US UK US UK US UK US UKFelbamate* No NA No NA Yes† NA Yes NA No NA Yes† NAGabapentin Yes§ No No No Yes Yes¶ No No No No No NoLamotrigine Yes§ Yes|| Yes§ Yes|| Yes Yes** Yes Yes No Yes** Yes Yes**Levetiracetam No No No No Yes Yes†† No No No No No NoOxcarbazepine Yes Yes¶ No No Yes Yes¶ Yes Yes¶ No No No NoTiagabine No No No No Yes Yes|| No No No No No NoTopiramate Yes§ Yes¶ No No Yes Yes** Yes§ Yes¶ Yes†† Yes††** Yes Yes**Vigabatrin§§ NA No NA No NA Yes NA No NA No NA Yes¶¶Zonisamide No NA No NA Yes|||| NA No NA No NA No NANoneofthedrugsisrecommendedasfirstchoiceinnewlydiagnosedepilepsybytheUKguidelines(seetext).NA=notavailable.*PatientsUnresponsivetostandarddrugsinWhomtherisk/benefitratiosupportsuse;†onlypatients>18years;

‡onlypatients>4yearswithLennox-Gastautayndrome;§indicationnotapprovedFDA;¶onlypatients≥6years;||onlypatients≥12years;**onlypatients>2years;††onlypatients≥16years;††onlygeneralizedtonic-clonicseizures;§§intheUKtheindicationsarelimitedtoadjunctiveuseafterfailureofallotherappropriatedrugcombinations;¶¶onlyWestayndrome;||||onlyadulte.新药的严重/非严重不良事件LancetNeurol2004;3:618–21AED Seriousadversevevnts NonseriousadverseFelbamate Aplasticanaemia,hepatotoxicity Gastrointestinaldisturbancse,anorexia,insomniaGabapentin Aggresion* Weightgain,peripheralcedema,behaviouralchanges†Lamotrigine Rash,includingStevensJohnsonandtoxicepidermalnecrolysis Tics†andinsomnia (highriskforchildren,alsomorecommonwithconcomitant vaiproic-aciduseandlowwithslowtitration);hypereensitivity reactions,includinghepaticandrenalfailure,DIC,andarthritisLevetiracetam None Irritability/behaviourchangeOxcarbazepine Hyponatraemia(morecommoninelderlypeople),rash NoneTiagabine Nonconvulsivestatusepilepticus Dizziness,astheniaTopiramate Nephrolithiasis,openangleglaucoma,hypohidrosis,† Metabolicacidosis,weightloss, depression,psychosis languagedysfunxtion,paraesthesiaVigabatrin Visualfielddefects,psychosis,depression WeightgainZonisamide Rash,renalcalculi,hypohidrosis† Irritability,photosensitivity,weightlossAED=antiepticdrug;DIC=disseminatedintravascularcoagulation.*Mosthyincognitivelyimpairedpatients;†predominantlychildren.临床医生在应用指南时特别注意

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要特别注意癫痫药物加重癫痫发作400-0120-772沈阳万佳癫痫医院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:治疗无效的时间,意向性治疗集

Log-RankChi-square=22.150,df=3,p<0.0001

-O-LTG-O-CBZ-O-TPM-O-GBP时间(天)继续治疗的比例Ref:SANAD研究结果结论

研究A拉莫三嗪治疗无效的比例显著低于卡马西平,

加巴喷丁,

托吡酯拉莫三嗪的疗效与卡马西平相似且并不低于卡马西平拉莫三嗪对于部分性发作的患者可考虑为第一线药物Ref:SANAD研究结果研究B:治疗无效的时间Log-RankChi-square=10.117,df=2,p=0.006-O-VPS-O-LTG-O-TPM继续治疗的比例时间(天)Ref:SANAD研究结果结论

研究B丙戊酸的疗效显著高于拉莫三嗪和托吡酯丙戊酸和拉莫三嗪的耐受性高于托吡酯丙戊酸对于全身发作或未分类的发作的患者可考虑为第一线药物传统抗癫痫药与新型抗癫痫药在疗效上无显著差异KwanP,BrodieMJ.NEnglMed.2000;342:314-3150%10%20%30%40%50%60%70%80%Patientsseizurefreefor≥1yearTraditionalAED(n=289)NewAED(n=134)Patientstreatedwith1AEDP=NS67%69%70%10%0%PersistentseizuresSeizurefreefor≥1yearPatientswithepilepsy(n-525)60%50%40%30%20%Patients63%37%289werereceivinganestablisheddrug(155werereceivingcarbamazepine,125valproatesodium,8phenytoin,and1ethosuximid