内科-神经内科-癫痫治疗指南新看点

抗癫痫药物临床治疗指南新看点华山医院俞丽云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：不断更新抗癫痫治疗指南大事记发布机构发布年限苏格兰临床指导协作组(SIGN)2003英国临床优化研究所（NICE）2004美国神经学会（AAN）美国癫痫学会（AES）2004ILAE2006Payakachatetal.JManagCarePharma2006WelcometotheNationalInstituteforHealthandClinicalExcellencewebsiteNICEistheindependentorganizationresponsibleforprovidingnationalguidanceonthepromotionofgoodhealthandthepreventionandtreatmentofillhealth.On1April2005NICEjoinedwiththeHealthDevelopmentAgencytobecomethenewNationalInstituteforHealthandClinicalExcellence(alsotobeknownasNICE).ClinicalExcellencePublicHealthExcellenceNICEwassetupasaSpecialHealthAuthorityforEnglandandWaleson1April1999.Itsroleistoprovidepatients,healthprofessionalsandthepublicwithauthoritative,robustandreliableguidanceoncurrent‘bestpractice’.()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:•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NICE指南Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat: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:•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: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):1252-1260Neurology.2004,62(8):1261-1273AAN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×Payakachatetal.JManagCarePharma2006Payakachatetal.JManagCarePharma2006AEDsasMonotherapyofPartial/MixGeneralizedTonic-ClonicSeizureANN*NICE†SIGN‡Phenobarital1st¶--Carbamazepine(genericTegretol)TegretolXR1st1st1stPhenytoin(genericDilantin)1st1st-Valproicacid(genericDepakene)Divalproex(Depakote)Divalproex(DepakoteER)1st1st1stPrimidone(genericMysoline)---Gabapentin(genericNeurontin)1st--Zonisamide)Zonegran)---Tiagabine(Gabitril)---Oxcarbazepine(Trileptal)1st2nd1stTopiramate(Topamax)1st2nd-Levetiracetam(Keppra)---Lamotrigine(Lamictal)1st2nd1stNICE指南和AAN指南对于新药的使用推荐LancetNeurol2004;3:618–21DrugNewlydiagnosedepilepsyRefractoryepilepsyPartialAbsencePartialPartialIdiopathicSymptomatiemixedmonotherapygeneralisedgeneralisedUSUKUSUKUSUKUSUKUSUKUSUKFelbamate*NoNANoNAYes†NAYesNANoNAYes†NAGabapentinYes§NoNoNoYesYes¶NoNoNoNoNoNoLamotrigineYes§Yes||Yes§Yes||YesYes**YesYesNoYes**YesYes**LevetiracetamNoNoNoNoYesYes††NoNoNoNoNoNoOxcarbazepineYesYes¶NoNoYesYes¶YesYes¶NoNoNoNoTiagabineNoNoNoNoYesYes||NoNoNoNoNoNoTopiramateYes§Yes¶NoNoYesYes**Yes§Yes¶Yes††Yes††**YesYes**Vigabatrin§§NANoNANoNAYesNANoNANoNAYes¶¶ZonisamideNoNANoNAYes||||NANoNANoNANoNANoneofthedrugsisrecommendedasfirstchoiceinnewlydiagnosedepilepsybytheUKguidelines(seetext).NA=notavailable.*PatientsUnresponsivetostandarddrugsinWhomtherisk/benefitratiosupportsuse;†onlypatients18years;‡onlypatients4yearswithLennox-Gastautayndrome;§indicationnotapprovedFDA;¶onlypatients≥6years;||onlypatients≥12years;**onlypatients2years;††onlypatients≥16years;††onlygeneralizedtonic-clonicseizures;§§intheUKtheindicationsarelimitedtoadjunctiveuseafterfailureofallotherappropriatedrugcombinations;¶¶onlyWestayndrome;||||onlyadulte.新药的严重/非严重不良事件LancetNeurol2004;3:618–21AEDSeriousadversevevntsNonseriousadverseFelbamateAplasticanaemia,hepatotoxicityGastrointestinaldisturbancse,anorexia,insomniaGabapentinAggresion*Weightgain,peripheralcedema,behaviouralchanges†LamotrigineRash,includingStevensJohnsonandtoxicepidermalnecrolysisTics†andinsomnia(highriskforchildren,alsomorecommonwithconcomitantvaiproic-aciduseandlowwithslowtitration);hypereensitivityreactions,includinghepaticandrenalfailure,DIC,andarthritisLevetiracetamNoneIrritability/behaviourchangeOxcarbazepineHyponatraemia(morecommoninelderlypeople),rashNoneTiagabineNonconvulsivestatusepilepticusDizziness,astheniaTopiramateNephrolithiasis,openangleglaucoma,hypohidrosis,†Metabolicacidosis,weightloss,depression,psychosislanguagedysfunxtion,paraesthesiaVigabatrinVisualfielddefects,psychosis,depressionWeightgainZonisamideRash,renalcalculi,hypohidrosis†Irritability,photosensitivity,weightlossAED=antiepticdrug;DIC=disseminatedintravascularcoagulation.*Mosthyincognitivelyimpairedpatients;†predominantlychildren.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