內(nèi)科-神經(jīng)內(nèi)科-癲癇治療指南新看點(diǎn).ppt

抗癲癇藥物臨床治療指南新看點(diǎn),華山醫(yī)院 俞麗云,制訂臨床指南的目的,應(yīng)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(duì)于特定臨床情況作出適當(dāng)?shù)尼t(yī)療決定,臨床指南的存在問題,1.評(píng)估標(biāo)準(zhǔn)不統(tǒng)一 2.缺乏證據(jù)不存在的證據(jù) 3.時(shí)間局限性過時(shí)、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(gè)體差異 7.臨床醫(yī)生執(zhí)行時(shí)困難,Shorvon S. Epilepsia 2006,4).10913,制訂指南原則,透明：無(wú)利益驅(qū)動(dòng) 公平：所有數(shù)據(jù)采用同樣的評(píng)估標(biāo)準(zhǔn) 嚴(yán)格：評(píng)價(jià)方法嚴(yán)格可行 動(dòng)態(tài)：不斷更新,抗癲癇治療指南大事記,Payakachat et al. J Manag Care Pharma 2006,NICE was set up as a Special Health Authority for England and Wales on 1 April 1999. Its role is to provide patients, health professionals and the public with authoritative, robust and reliable guidance on current best practice. (.uk/),NICE指南,對(duì)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(yīng)推薦,Ref: National Institute for Health and Clinical Excellence. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: .uk/TA076guidance. Accessed July 5, 2005.,NICE在治療中 盡可能選擇單藥治療 不推薦常規(guī)監(jiān)測(cè)看癲癇藥物的血藥濃度 停藥原則,NICE指南,Ref: National Institute for Health and Clinical Excellence. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: .uk/TA076guidance. Accessed July 5, 2005.,NICE指南,目前仍缺乏高質(zhì)量的臨床試驗(yàn)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(jié)果支持新藥優(yōu)于傳統(tǒng)藥物 僅9項(xiàng)比較新藥和老藥單藥治療新診斷癲癇患者生活質(zhì)量的研究，未提供強(qiáng)有力的證據(jù)支持新藥提高患者生活質(zhì)量 傳統(tǒng)抗癲癇藥物單藥治療費(fèi)用更便宜,Ref: National Institute for Health and Clinical Excellence. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: .uk/TA076guidance. Accessed July 5, 2005.,首選單藥治療藥物應(yīng)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(duì)該藥耐受性差 患者處于準(zhǔn)備生育期 新型抗癲癇藥物作為初始治療的二線選擇,Ref: National Institute for Health and Clinical Excellence. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: .uk/TA076guidance. Accessed July 5, 2005.,NICE指南,NICE缺點(diǎn) 1.評(píng)定的證據(jù)標(biāo)準(zhǔn)和證據(jù)分類沒有明確的描述 2.傳統(tǒng)抗癲癇藥沒有進(jìn)行同樣的評(píng)估,NICE指南,Neurology. 2004,62(8):1252-1260,Neurology. 2004,62(8):1261-1273,AAN指南,1. AAN指南有明確證據(jù)分類和證據(jù)評(píng)級(jí) 2. 以有效性作為主要評(píng)估指標(biāo) 3. 缺點(diǎn)： 未評(píng)估傳統(tǒng)藥物 生活質(zhì)量和成本效益未作為參考指標(biāo),抗癲癇臨床治療指南比較總結(jié),Payakachat et al. J Manag Care Pharma 2006,Payakachat et al. J Manag Care Pharma 2006,NICE指南和AAN指南對(duì)于新藥的使用推薦,Lancet Neurol 2004; 3: 61821,Drug Newly diagnosed epilepsy Refractory epilepsy Partial Absence Partial Partial Idiopathic Symptomatie mixed monotherapy generalised generalised US UK US UK US UK US UK US UK US UK Felbamate* No NA No NA Yes NA Yes NA No NA Yes NA Gabapentin Yes No No No Yes Yes No No No No No No Lamotrigine Yes Yes| Yes Yes| Yes Yes* Yes Yes No Yes* Yes Yes* Levetiracetam No No No No Yes Yes No No No No No No Oxcarbazepine Yes Yes No No Yes Yes Yes Yes No No No No Tiagabine No No No No Yes Yes| No No No No No No Topiramate 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 NA,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.,新藥的嚴(yán)重/非嚴(yán)重不良事件,Lancet Neurol 2004; 3: 61821,AED Serious adverse vevnts Nonserious adverse Felbamate Aplastic anaemia, hepatotoxicity Gastrointestinal disturbancse, anorexia, insomnia Gabapentin Aggresion* Weight gain, peripheral cedema, behavioural changes Lamotrigine Rash, including Stevens Johnson and toxic epidermal necrolysis Tics 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 Levetiracetam None Irritability/behaviour change Oxcarbazepine Hyponatraemia (more common in elderly people), rash None Tiagabine Nonconvulsive status epilepticus Dizziness, asthenia Topiramate Nephrolithiasis, open angle glaucoma, hypohidrosis, Metabolic acidosis, weight loss, depression, psychosis language dysfunxtion, paraesthesia Vigabatrin Visual field defects, psychosis, depression Weight gain Zonisamide Rash, 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(píng)估標(biāo)準(zhǔn) 2. 制定指南的目的差異,臨床醫(yī)生在應(yīng)用指南時(shí)特別注意,臨床醫(yī)生在應(yīng)用指南時(shí)特別注意,要特別注意癲癇藥物加重癲癇發(fā)作,可能加重某些癲癇綜合征的抗癇藥物,Ref: Epilepsia. 39(Suppl. 3):S15-S18, 1998,Elger等對(duì)1006例局灶性癲癇 （包括單藥和添加治療）薈萃分析,抗癲癇藥物惡化發(fā)作,癲癇患者發(fā)作增加的百分比,臨床醫(yī)生在應(yīng)用指南時(shí)特別注意,治療要個(gè)體化,要特別關(guān)注特殊人群:兒童、婦女、老人,臨床醫(yī)生在應(yīng)用指南時(shí)特別注意,認(rèn)識(shí)的更新 SANAD試驗(yàn)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: 基線的人口學(xué)資料和臨床表現(xiàn),Ref: SANAD研究結(jié)果,研究A:治療無(wú)效的時(shí)間, 意向性治療集 Log-Rank Chi-square=22.150, df= 3, p0.0001,-O- LTG -O- CBZ -O- TPM -O- GBP,繼續(xù)治療的比例,結(jié)論 研究 A,拉莫三嗪治療無(wú)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(duì)于部分性發(fā)作的患者可考慮為第一線藥物,Ref: SANAD研究結(jié)果,研究B:基線的人口學(xué)資料和臨床表現(xiàn),Ref: SANAD研究結(jié)果,研究B:治療無(wú)效的時(shí)間 Log-Rank Chi-square=10.117, df= 2, p=0.006,-O- VPS -O- LTG -O- TPM,繼續(xù)治療的比例,時(shí)間 (天),Ref: SANAD研究結(jié)果,結(jié)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(duì)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(wú)顯著差異,Kwan P, Brodie MJ. N Engl Med. 2000; 342:314-315,289 were receiving an established drug (155 were receiving carbamazepine, 125 valproate sodium, 8 phenytoin, and 1 ethosuximide), 134 were taking one of the newer antiepileptic drugs (99 were receiving lamotrigine, 15 gabapentin, 7 oxcarbazepine, 9 tiagabine, 3 topiramate, and 1 vigabatrin).,傳統(tǒng)抗癲癇藥與新型抗癲癇藥在療效上無(wú)顯著差異,N Engl J Med 2000;342:314-9.,470 patients has never received An antiepileptic drug before (64% seizure-free),Epilepsy was not controlled by 1st antiepileptic drug in 248; 168 receved an established drug and 80 received a new drug,69 Had