癲癇病制訂臨床指南的目的課件

制訂臨床指南的目的

應用指南是一種系統(tǒng)性闡述，用以幫助職業(yè)醫(yī)師以及患者對于特定臨床情況作出適當?shù)尼t(yī)療決定400-0196-638廣州協(xié)佳癲癇醫(yī)院臨床指南的存在問題1.評估標準不統(tǒng)一2.缺乏證據(jù)≠不存在的證據(jù)3.時間局限性→過時、更新4.受到藥廠的影響，有一定的利益因素5.由少部分專家制定6.個體差異7.臨床醫(yī)生執(zhí)行時困難ShorvonS.Epilepsia2006,4).1091~3制訂指南原則透明：無利益驅動公平：所有數(shù)據(jù)采用同樣的評估標準嚴格：評價方法嚴格可行動態(tài)：不斷更新NICE指南對于抗癲癇藥物使用的指證，藥物選擇，換藥，停藥等原則性問題均作出了相應推薦Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.NICE指南NICE在治療中①盡可能選擇單藥治療②不推薦常規(guī)監(jiān)測看癲癇藥物的血藥濃度③停藥原則Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.NICE指南目前仍缺乏高質量的臨床試驗支持新藥單藥治療比傳統(tǒng)藥物更有效研究中的藥物副作用和耐受性并未提供足夠多且一致的結果支持新藥優(yōu)于傳統(tǒng)藥物僅9項比較新藥和老藥單藥治療新診斷癲癇患者生活質量的研究，未提供強有力的證據(jù)支持新藥提高患者生活質量傳統(tǒng)抗癲癇藥物單藥治療費用更便宜Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.400-0059-826昆明軍海腦科醫(yī)院NICE指南首選單藥治療藥物應為傳統(tǒng)抗癲癇藥物如丙戊酸鈉或卡馬西平，除如下原因:禁忌癥與患者目前服用的藥物有潛在的相互作用患者在既往治療中對該藥耐受性差患者處于準備生育期新型抗癲癇藥物作為初始治療的二線選擇Ref:NationalInstituteforHealthandClinicalExcellence.Technologyappraisalguidance76:newerdrugsforepilepsyinadults.Availableat:.uk/TA076guidance.AccessedJuly5,2005.Neurology.2004,62(8):1252-1260Neurology.2004,62(8):1261-1273抗癲癇臨床治療指南比較總結評價指標NICE指南AAN指南有效性安全性生活質量×成本效益×Payakachatetal.JManagCarePharma2006400-0120-772沈陽萬佳癲癇醫(yī)院NICE指南和AAN指南對于新藥的使用推薦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.新藥的嚴重/非嚴重不良事件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.臨床醫(yī)生在應用指南時特別注意

上述各抗癲癇藥治療指南的差異在于單藥治療的推薦上（新藥與傳統(tǒng)藥）

原因：1.證據(jù)的評估標準

2.制定指南的目的差異臨床醫(yī)生在應用指南時特別注意要特別注意癲癇藥物加重癲癇發(fā)作400-0120-772沈陽萬佳癲癇醫(yī)院可能加重某些癲癇綜合征的抗癇藥物藥物綜合癥可能加重的情況卡馬西平失神癲癇肌陣攣、失神發(fā)作青少年肌陣攣癲癇肌陣攣性發(fā)作進行性肌陣攣癲癇肌陣攣中央回癲癇CSWS.肌陣攣苯巴英鈉失神癲癇失神發(fā)作進行性肌陣攣癲癇小腦綜合癥，肌陣攣苯巴比妥失神癲癇大劑量時失神發(fā)作苯二氮卓類藥物LGS強直性發(fā)作氨已烯酸失神癲癇失神發(fā)作伴肌陣攣的癲癇肌陣攣加巴噴丁失神癲癇失神發(fā)作伴肌陣攣的癲癇肌陣攣拉莫三嗪嚴重的肌陣攣癲癇大劑量時GTCS青少年肌陣攣癲癇肌陣攣性發(fā)作臨床醫(yī)生在應用指南時特別注意治療要個體化,要特別關注特殊人群:兒童、婦女、老人臨床醫(yī)生在應用指南時特別注意

認識的更新

SANAD試驗發(fā)現(xiàn)丙戊酸和其它新抗癲癇藥在癲癇治療的綜合作用中明顯優(yōu)于其它藥物研究A:治療無效的時間,意向性治療集

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

-O-LTG-O-CBZ-O-TPM-O-GBP時間(天)繼續(xù)治療的比例Ref:SANAD研究結果結論

研究A拉莫三嗪治療無效的比例顯著低于卡馬西平,

加巴噴丁,

托吡酯拉莫三嗪的療效與卡馬西平相似且并不低于卡馬西平拉莫三嗪對于部分性發(fā)作的患者可考慮為第一線藥物Ref:SANAD研究結果研究B:治療無效的時間Log-RankChi-square=10.117,df=2,p=0.006-O-VPS-O-LTG-O-TPM繼續(xù)治療的比例時間(天)Ref:SANAD研究結果結論

研究B丙戊酸的療效顯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對于全身發(fā)作或未分類的發(fā)作的患者可考慮為第一線藥物傳統(tǒng)抗癲癇藥與新型抗癲癇藥在療效上無顯著差異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