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1、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,Shorvon S. Epilepsia 2006,4).10913,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,Payakachat et al. J Manag Car
2、e 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. (http:/www.nice.org.uk/),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
3、则性问题均作出了相应推荐,Ref: National Institute for Health and Clinical Excellence. Technology appraisal 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 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 停药原则,NICE指南,Ref: National Institute for Health
4、 and Clinical Excellence. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: http:/www.nice.org.uk/TA076guidance. Accessed July 5, 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
5、药物单药治疗费用更便宜,Ref: National Institute for Health and Clinical Excellence. Technology appraisal guidance 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
6、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. Technology appraisal guidance 76: newer drugs for epilepsy in adults. Available at: http:/www.nice.org.uk/TA076guidance. Accessed July 5, 2005.,NICE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,
7、62(8):1252-1260,Neurology. 2004,62(8):1261-1273,AAN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,Payakachat et al. J Manag Care Pharma 2006,Payakachat et al. J Manag Care Pharma 2006,NICE指南和AAN指南对于新药的使用推荐,Lancet Neurol 2004; 3: 61821,Drug Newly diagnosed epile
8、psy 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
9、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
10、 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
11、 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 combinat
12、ions; only West ayndrome; | only adulte.,新药的严重/非严重不良事件,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 Lam
13、otrigine 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
14、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 dysfunxti
15、on, 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 childr
16、en.,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,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,可能加重某些癫痫综合征的抗痫药物,Ref: Epilepsia. 39(Suppl. 3):S15-S18, 1998,Elger等对1006例局灶性癫痫 （包括单药和添加治疗）荟萃分析,抗癫痫药物恶化发作,癫痫患者发作增加的百分比,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: 基线的人口学资料和临床表现,Ref: SANAD研究结果,研究A:治疗无
