1、抗癫痫药物临床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制订临床指南的目的 应用指南是一种系统性阐述,应用指南是一种系统性阐述,用以帮助职业医师以及患者用以帮助职业医师以及患者对于特定临床情况作出适当对于特定临床情况作出适当的医疗决定的医疗决定NICE指南指南对于抗癫痫药物使用的指证,药物选择,换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药,停药等原则性问题均作出了相应推荐Ref: National Institute for Health and Clinical Excellence. Technology appraisal
2、guidance 76: newer drugs for epilepsy in adults. Available at:http:/www.nice.org.uk/TA076guidance. Accessed July 5, 2005.NICE在治疗中在治疗中尽可能选择单药治疗尽可能选择单药治疗不推荐常规监测看癫痫药物的血药浓度不推荐常规监测看癫痫药物的血药浓度停药原则停药原则NICE指南指南Ref: National Institute for Health and Clinical Excellence. Technology appraisalguidance 76: newer
3、drugs for epilepsy in adults. Available at:http:/www.nice.org.uk/TA076guidance. Accessed July 5, 2005.NICE指南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.
4、 Technology appraisalguidance 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. T
5、echnology appraisalguidance 76: newer drugs for epilepsy in adults. Available at:http:/www.nice.org.uk/TA076guidance. Accessed July 5, 2005.NICE指南指南NICE缺点缺点1.评定的证据标准和证据分类没有明确的描述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传统抗癫痫药没有进行同样的评估NICE指南指南Neurology. 2004,62(8):1252-1260 Neurology. 2004,62(8):1252-1260
6、Neurology. 2004,62(8):1261-1273Neurology. 2004,62(8):1261-1273AAN指南指南1. AAN指南有明确证据分类和证据评级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以有效性作为主要评估指标3. 缺点:缺点: 未评估传统药物未评估传统药物 生活质量和成本效益未作为参考指标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Payakachat et al. J Manag Care Pharma 2006Payakachat et al. J Manag Care Pharma 2006NICE指南和AAN指南对于新药
7、的使用推荐Lancet Neurol 2004; 3: 61821DrugDrugNewly diagnosed epilepsyNewly diagnosed epilepsyRefractory epilepsy Refractory epilepsy PartialPartialAbsenceAbsencePartialPartialPartialPartialIdiopathicIdiopathicSymptomatieSymptomatiemixedmixedmonotherapymonotherapygeneralisedgeneralisedgeneralisedgenerali
8、sedUSUSUKUKUSUSUKUKUSUSUKUKUSUSUKUKUSUSUKUKUSUSUKUKFelbamate*Felbamate*NoNoNANANoNoNANAYesYesNANAYesYesNANANoNoNANAYes Yes NANAGabapentinGabapentinYesYes NoNoNoNoNoNoYesYesYesYesNoNoNoNoNoNoNoNoNoNoNoNoLamotrigineLamotrigineYesYes Yes|Yes|YesYes Yes|Yes|YesYesYes*Yes*YesYesYesYesNo No Yes*Yes*YesYes
9、Yes*Yes*LevetiracetamLevetiracetamNoNoNoNoNoNoNoNoYesYesYesYesNoNoNoNoNoNoNoNoNoNoNoNoOxcarbazepineOxcarbazepineYesYesYesYesNoNoNoNoYesYesYesYesYesYesYesYesNoNoNoNoNoNoNoNoTiagabineTiagabineNoNoNoNoNoNoNoNoYesYesYes|Yes|NoNoNoNoNoNoNoNoNoNoNoNoTopiramateTopiramateYesYes Yes Yes NoNoNoNoYesYesYes*Yes
10、*YesYes YesYesYesYesYes*Yes*YesYesYes*Yes*VigabatrinVigabatrinNANANoNoNANANoNoNANAYesYesNANANoNoNANANoNoNANAYesYesZonisamideZonisamideNoNoNANANo No NANAYes|Yes|NANANoNoNANANoNoNANANoNoNANANone of the drugs is recommended as first choice in newly diagnosed epilepsy by the UK guidelines (see text). NA
11、=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 16yea
12、rs; 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. 新药的严重新药的严重/非严重不良事件非严重不良事件Lancet Neurol 2004; 3: 61821AEDAEDSerious adverse vevntsSerious adverse vevntsNons
13、erious adverseNonserious adverseFelbamateFelbamateAplastic anaemia, hepatotoxicityAplastic anaemia, hepatotoxicityGastrointestinal disturbancse, anorexia, insomniaGastrointestinal disturbancse, anorexia, insomniaGabapentinGabapentinAggresion*Aggresion*Weight gain, peripheral cedema, behavioural chan
14、ges Weight gain, peripheral cedema, behavioural changes LamotrigineLamotrigineRash, including Stevens Johnson and toxic epidermal necrolysisRash, including Stevens Johnson and toxic epidermal necrolysisTics and insomniaTics and insomnia(high risk for children, also more common with concomitant(high
15、risk for children, also more common with concomitantvaiproic-acid use and low with slow titration); hypereensitivityvaiproic-acid use and low with slow titration); hypereensitivityreactions, including hepatic and renal failure, DIC, and arthritisreactions, including hepatic and renal failure, DIC, a
16、nd arthritisLevetiracetamLevetiracetamNoneNoneIrritability/behaviour changeIrritability/behaviour changeOxcarbazepineOxcarbazepine Hyponatraemia (more common in elderly people), rashHyponatraemia (more common in elderly people), rashNoneNoneTiagabineTiagabineNonconvulsive status epilepticusNonconvulsive status epilepticusDizziness, astheniaDizziness, astheniaTopiramate Topiramate Nephrolithiasis, open angle glaucoma, hypohidrosis,Nephrolithiasis, open angle glaucoma, hypohidrosis,Metabolic acido