癫(癎)患者撤药的研究现状

癫(癎)是神经科常见疾病,许多患者需长期服用抗癫(癎)药物(AEDs).AEDs虽能预防癫(癎)发作,但也可产生不同类型和程度的不良反应.因此,当癫(癎)缓解达一定时间,患者及其家属最关心的是撤药问题.及时而合理的撤药对癫(癎)患者的预后、避免不必要的不良反应、提高生活质量将有重要影响.为此,现对缓解期癫(癎)患者撤药问题的相关研究综述如下.     

229例癫癎无发作2年以上患者的脑电图特点及影响因素

目的探讨癫癎无发作2年以上的患者抗癫癎药(AEDs)撤药前脑电图异常(样放电)的可能影响因素。方法根据入组标准共筛选229例癫癎控制、达到无发作2年以上患者,收集相关临床资料并进行统计学分析。结果在229例患者中,脑电图持续异常者为48例(21.0%)。多因素分析发现首次发作后脑电图出现异常放电(P=0.000,OR=9.07,95%CI:3.39-24.28)以及多药联合治疗(P=0.019,OR=2.70,95%CI:1.17-6.17)是脑电图持续异常(样放电)的相关危险因素。结论癫癎首次发作后脑电图异常(样放电)、AEDs多药联合治疗是癫癎发作控制患者的脑电图持续异常(样放电)的危险因素,撤药应慎重。     

抗癫药物对妊娠癫癎患者子代的致畸风险

目的:旨在评估抗癫癎药物(AEDs)对妊娠癫癎患者子代出现先天畸形的风险。方法:对妊娠癫癎患者采用登记和随访研究,分析其孕期AEDs用药情况、癫癎发作、妊娠结局及子代出现畸形的风险。结果:入选105例妊娠癫癎患者。服用AEDs患者79/105例(75.2%),未服用AEDs患者26/105例(24.8%)。单药治疗60/79例(75.9%),其中1/60例(1.7%)流产;患者子代中2/60例(3.3%)先天性畸形(1例服用卡马西平,出现先天性心脏动脉导管未闭;1例服用拉莫三嗪,出现无胚心)。联合用药19/79例(24.1%),子代无先天畸形出现。未服用AEDs患者中有2/26例(7.7%)流产,其余患者子代未出现先天畸形。结论:妊娠癫癎孕妇多数于孕期仍服用AEDs,且以单药治疗居多;使用AEDs(分别为卡马西平和拉莫三嗪)患者子代出现2例先天性畸形;丙戊酸钠易致畸但仍在妊娠癫癎中经常使用,本研究中服用丙戊酸钠孕妇未出现子代先天性畸形。     

癫癎患者认知功能障碍及其影响因素分析

目的探讨癫癎患者认知功能障碍及其影响因素。方法采用韦氏儿童智力量表、成人智力量表对102例癫癎患者的认知功能进行评估,分析发病年龄、发作频率、发作时相、服用抗癫癎药物(AEDs)种类等因素对认知的影响。结果韦氏智力量表评估提示癫癎患者认知功能障碍发生率为82.2%。单因素差异分析显示发作频率、发作时相、单药治疗和多药治疗、服用AEDs种类均与认知功能损害程度相关。结论癫癎患者存在明显的认知功能障碍,发作频率、发作时相、AEDs服用情况均是影响癫癎患者认知功能的主要因素。     

抗癫癎药物对癫癎发作后状态影响研究进展

癫癎发作后状态(PIS)是癫癎发作结束后患者的综合临床表现。PIS与癫癎患者持续的认知功能变化,抗癫癎药物(AEDs)的选择及长期保留率有关,并影响患者生活质量。新、老AEDs对PIS的冶疗效果至今未被明确阐述。目前,AEDs对PIS的疗效已被引起重视,并逐步纳入AEDs总体评价指标。本文对此进行综述。     

癫患者初次治疗及撤药的时机与方法

癫(癎)患者一旦确诊,何时开始药物治疗、治疗有效后何时撤药及其方法是癫(癎)正规治疗中的重要问题,对此临床医师、癫(癎)患者及其家属都极为关心.及时合理地决定用药和撤药时机对患者的预后、避免不必要的药物不良反应以及生活质量将产生重要影响.然而,目前临床医师往往依据临床经验来决定癫(癎)患者的初次用药和撤药的时机,缺乏循证医学的依据,现对此综述如下.……     

癫(癎)患者初次治疗及撤药的时机与方法

癫(癎)患者一旦确诊,何时开始药物治疗、治疗有效后何时撤药及其方法是癫(癎)正规治疗中的重要问题,对此临床医师、癫(癎)患者及其家属都极为关心.及时合理地决定用药和撤药时机对患者的预后、避免不必要的药物不良反应以及生活质量将产生重要影响.然而,目前临床医师往往依据临床经验来决定癫(癎)患者的初次用药和撤药的时机,缺乏循证医学的依据,现对此综述如下.     

抗癫癎药物致癎作用的临床观察

目的研究抗癫癎药物(AEDs)的致癎作用及对其的预防和治疗.方法总结32例AEDs致癫癎发作加重患者的临床资料.结果32例中以服用卡马西平最多(19.12%)、次之为巴比妥类药物(15%)、苯妥英钠(14.5%)、合并用药(14.29%)、苯二氮( )类(8.69%)、丙戊酸钠(2.78%).32例经停药并合理选择其他抗癫癎药物及减少药物剂量治疗,27例有效,5例无效.结论AEDs能致癫癎发作加重,应合理选择抗癫癎药物.     

香草醛治疗癫(疒间)的疗效观察

癫癎为一组比较难治的病症,经传统的抗癫癎药(AEDs)系统、正规治疗,仍有20%～30%的患者发作不能控制.为寻找新的有效的AEDs,国内的医药工作者研制的香草醛,经动物实验及临床验证其有较好的抗癫癎作用[1,2].我们自2004-03～2004-12用香草醛治疗各型癫癎31例,取得初步疗效,现将结果报告如下.     

癫(癎)减停药后复发危险因素分析

目的 回顾性分析癫(癎)发作获得控制患者减停药后复发情况及相关危险因素,以为临床应用提供参考依据.方法 采用单因素分析和向前逐步法多因素非条件Logistic回归分析评价311例癫(癎)发作获得控制且减停药≥2年患者的癫(癎)复发危险因素.结果 311例患者,癫(癎)复发率为34.73%(108/311),其中在医师指导下减停药者280例,癫(癎)复发率为29.29%(82/280),停药后1年内复发率为26.43%(74/280),停药后2年内复发率为28.21%(79/280).单因素分析结果显示,青少年期发病、成年期发病、肌阵挛发作、青少年肌阵挛癫(癎)、症状性部分性癫(癎)、减药前大发作频率>10次、成年期减药、成人减药前无发作时间<4年、减药时间<6个月及减药前脑电图显示(癎)样放电共10项因素是减停药后癫(癎)复发的危险因索,差异具有统计学意义(均P<0.05).多因素非条件Logistic回归分析结果显示,青少年期发病、成年期发病、青少年肌阵挛癫(癎)、症状性部分性癫(癎)、成人减药前无发作时间<4年、减药时间<6个月及减药前脑电图显示(癎)样放电为减停药后癫(癎)复发的主要危险因素(均P<0.05).结论 癫(癎)减停药应该注重个体化原则.儿童期发病的癫(癎)患者发作控制1～2年可考虑减停药,成年患者发作控制>4年方可考虑减停药,减药时间应≥6个月.青少年期发病、成年期发病、青少年肌阵挛癫(癎)、症状性部分性癫(癎)及减药前脑电图显示(癎)样放电者,减停药后癫(癎)复发风险高,减停药需慎重.     

癫痫无发作患者撤药后的长期结局及复发的危险因素分析

目的 探讨癫痫无发作患者撤药后的长期结局及影响复发的危险因素。方法 本研究包含141例至少3年无发作的癫痫患者,自撤药开始随访至少3年或直到癫痫复发; 根据是否复发分为无发作组和复发组; 对连续变量和分类变量分别采用t检验和卡方检验。用多元回归分析复发危险因素。Kaplan-Meier生存曲线用来计算累积复发率。结果 141例患者中63例(44.7%)复发,78例(55.3%)在随访结束时仍无发作。平均复发时间是撤药后14个月,大多数复发在24个月内(81.0%); 撤药后的累积复发率在第6、12、24、36、48、60个月分别为19.1%、29.8%、36.2%、42.6%、43.4%、43.4%。单因素分析显示早期3个月内药物未控制发作组复发率高于早期3个月内药物控制发作组; 围产期损伤组复发率高于无围产期损伤组、需多药控制者组复发率高于单药控制组。进一步多因素回归分析发现有围产期损伤[风险比(HR)=5.000,95%置信区间(CI)=1.428～17.544]和需多药控制(HR=3.509,95% CI=1.545～8.000)是复发的独立危险因素。结论 癫痫复发主要发生在开始撤药后的前24个月,撤药后3年的无发作保留率为57.4%。撤药后复发的独立危险因素是有围产期损伤史和需多药控制。     

Long term course of childhood epilepsy following relapse after antiepileptic drug withdrawal

OBJECTIVE: To explore the course of epilepsy following relapse after antiepileptic drug (AED) withdrawal. METHODS: Forty two patients were identified with onset of epilepsy in childhood in whom AEDs had been withdrawn after at least 2 years of seizure freedom, and in whom a relapse had occurred. Two patients were lost to follow up. RESULTS: Median follow up after AED withdrawal was 5.9 years (range 1.6-13.2 years). Relapse occurred in more than half of the patients within 6 months of AED withdrawal. At the end of follow up, 12 patients (30%) were seizure free for at least 1 year (mean 10.4 years) without medication; 16 (40%) were seizure free for at least 1 year (mean 5.3 years) with ongoing medication; and 12 patients (30%) were seizure free for less than 1 year with medication. No status epilepticus occurred in any patient after withdrawal. Age at onset, if over the age of 5, combined with normal intelligence were predictive of an excellent outcome; presence of a neurological disorder, and hence symptomatic aetiology, was predictive of poor outcome after a relapse. CONCLUSIONS: Fears that premature withdrawal of AEDs might result in uncontrollable seizures were unsubstantiated in this study. The current practice of withdrawing AEDs in children who have been seizure free for 2 years can be beneficial to most of these patients.     

Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study)

OBJECTIVE: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health-related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied. METHODS: Patients, seizure-free for more than 2 years on AED monotherapy, were recruited for a controlled, prospective, randomized, double-blinded withdrawal study lasting for 12 months, or until seizure relapse. Patients were randomized to AED withdrawal (n = 79) and nonwithdrawal (n = 81) groups. The examination program included clinical neurological examinations, neuropsychological testing, EEG-recordings, cerebral MRI, and assessments of HRQOL. Follow-up data on seizure relapse were also collected beyond the 12-month study period (median 47 months). RESULTS: Seizure relapse at 12 months occurred in 15% of the withdrawal group and 7% of the nonwithdrawal group (RR 2.46; 95% CI: 0.85-7.08; p = 0.095). After withdrawal, seizure relapse rates were 27% after a median of 41 months off medication. A normal result to all 15 neuropsychological tests increased significantly from 11% to 28% postwithdrawal. We found no significant effects of withdrawal on quality of life and EEG. Predictors for remaining seizure-free after AED-withdrawal over 1 year were normal neurological examination and use of carbamazepine prior to withdrawal. CONCLUSION: Seizure-free epilepsy patients on AED monotherapy who taper their medication may improve neuropsychological performance with a relative risk of seizure relapse of 2.46, compared to those continuing therapy.     

四川地区新型抗癫痫药物超说明书规定用药分析：一项对儿童患者的多中心调查研究

目的调查四JII地区左乙拉西坦、托吡酯、奥卡西平和拉莫三嗪等新型抗癫痫药物在儿童癫痫患者中超说明书规定用药（超说明书用药）的现状及安全性,以为临床制定相关用药指南提供数据,并为临床用药提供参考。方法收集2010年7月一2011年11月于四JIl大学华西第二医院、成都市妇女儿童中心医院和四川I省人民医院门诊接受抗癫痫药物治疗的儿童癫痫患者资料,统计此间应用抗癫痫药物的总病例数和服用4种新型抗癫痫药物的病例数。依据药品说明书适应证,判断使用新型抗癫痫药物的医嘱是否属于超说明书用药及其药物类型,并计算和分析超说明书用药发生率及药物不良反应。结果共854例癫痫患儿接受抗癫痫药物治疗,其中670例患儿服用4种新型抗癫痴药物中的一种或多种,超说明书用药者406例,占抗癫痫药物治疗总病例数的47．54％（406／854）,约占新型抗癫痫药物治疗总病例数的60．60％（406／670）。与按说明书用药患儿相比,超说明书用药患儿年龄更小、单药使用比例更高、全面性发作和癫痫综合征患儿比例更高,其病例数比例分别为左乙拉西坦78．50％（157／200）、托吡酯79．81％（253／317）、奥卡西平21．32％（42／197）和拉莫三嗪33．33％（21／63）;不同年龄、单药使用和各种发作类型中以左乙拉西坦和托吡酯超说明书用药现象更为突出。除失访病例外,超说明书用药组患儿以奥卡西平[16．67％（7／42）]不良反应发生率最高,其次分别为托吡酯[14．81％（36／243）]、左乙拉西坦[10．60％（16／151）]和拉莫三嗪[9．52％（2／21）],但是与按说明书用药组之间差异无统计学意义（x2=0．375、0．448、0．014、0．109,P=0．540、0．503、0．906、0．742）。结论在四川地区儿童癫痫患者中超说明书应用新型抗癫痫药物的发生率较高,其中以托吡酯和左乙拉西坦尤为突出,但新型抗癫痫药物在一定范围内超说明书用药仍具有较好的安全性和耐受性。     

Slight improvement in mood and irritability after antiepileptic drug withdrawal: a controlled study in patients on monotherapy

OBJECTIVE: Most antiepileptic drugs (AEDs) are considered to have effects on mood and to be effective in a number of affective disorders. There are, however, conflicting reports in the literature with respect to the psychotropic properties of AEDs. Many of the studies have a number of methodological problems, and much uncertainty still exists regarding the behavioral and mood effects of AEDs. The aim of this study was to assess, in a randomized, double-blind, placebo-controlled study of seizure-free patients with epilepsy, the effect of withdrawal of AEDs in patients on monotherapy on measures of mood and behavior. METHODS: One hundred fifteen subjects who had been seizure-free >2 years on drug monotherapy went through a randomized, double-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Behavioral function was assessed with the Minnesota Multiphasic Personality Inventory 2 (MMPI-2) at baseline and 7 months after withdrawal. RESULTS: Discontinuation of AEDs resulted, to a greater extent than continued treatment, in a slight improvement in symptoms of depression and irritability. Comparable results were achieved in the subgroup taking carbamazepine. For patients with a high degree of depressive and somatic symptoms at baseline, no significant differences in symptoms emerged in the withdrawal group compared with the non-withdrawal group. CONCLUSION: The results suggest that seizure-free patients with epilepsy on monotherapy can obtain a slight improvement in symptoms characteristic of depression and irritability if they discontinue treatment with AEDs. The described changes are limited, and the functional impact is of uncertain significance.     

AED discontinuation may not be dangerous in seizure-free patients

The decision to continue or to stop anticonvulsant treatment in patients with prolonged seizure remission is still a matter of debate. There is no evidence that continued treatment guarantees permanent seizure freedom. Up to 50% of patients achieve terminal remission (i.e., off drugs). Almost one-half of patients with untreated epilepsy are seizure-free for more than 5 years and the number of those with continuing seizures tends to decrease over time. In contrast, a substantial fraction of patients on chronic treatment with antiepileptic drugs (AEDs) may be exposed to clinically relevant adverse effects. Other disadvantages of continuing treatment indefinitely include the teratogenic risk, drug interactions, and the concern that AEDs may be unnecessary. The probability of remaining seizure-free after treatment discontinuation is about 70% at 2 years. Although different combinations of factors are thought to affect the risk of relapse, the prediction of individual outcome before withdrawal remains uncertain. As a consequence, the decision to withdraw or withhold treatment must be still individualized. In any patient, the decision to discontinue treatment should also take into account social aspects like driving license, job and leisure activities as well as emotional and personal factors and adverse effects or drug interactions. Patients will ultimately have to decide themselves whether they wish to discontinue drug treatment.     

Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic localization-related epilepsies

The purpose of this study was to clarify the risk factors of relapse following discontinuation of AEDs in patients with childhood-onset cryptogenic localization-related epilepsies. The subjects were 82 patients who fulfilled the following criteria: (1) age at first visit of less than 15 years, (2) follow-up period of more than 5 years, (3) suffering from cryptogenic localization-related epilepsies, and (4) the patient underwent AED withdrawal during the follow-up period. As a basic principle, we decided to start withdrawing AEDs when both of the following two conditions were met: (1) the patient had a seizure-free period of 3 years or more, and (2) there were no epileptic discharges on EEGs just prior to the start of withdrawal. Seizures recurred in eight of the 82 patients (9.8%). Univariate analysis revealed that the following factors were correlated with higher rates of seizure relapse: 6 years of age or higher at onset of epilepsy; 15 years of age or higher at the start of AED withdrawal; 5 years or more from the start of AED treatment to seizure control; five or more seizures before seizure control; and two or more AEDs administered before seizure control. Among these risk factors, 6 years of age or higher at onset and 5 years or more from the start of AED treatment to seizure control were determined by multivariate analysis to be independent risk factors for relapse. Thus, we conclude that the physician should be more careful in discontinuing AEDs in these higher-risk patients groups, and more generous in discontinuing AEDs in lower-risk groups.     

Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy

OBJECTIVES: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. METHODS: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. RESULTS: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. CONCLUSIONS: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors.     

Reversible effects of antiepileptic drugs on reproductive endocrine function in men and women with epilepsy--a prospective randomized double-blind withdrawal study

PURPOSE: Epilepsy, antiepileptic drugs (AEDs), and reproductive endocrine function have complex interactions. In this study, we wanted to investigate the effects of AEDs on reproductive endocrine function after withdrawal of AEDs and look for reversible endocrine effects. METHODS: The study was prospective, randomized, and double-blinded. A total of 160 patients were included and randomized to withdrawal or not and 150 (80 females, 53%) patients went through the intervention and was included in the study for 12 months. Complete serum samples from before and 4 months after completed withdrawal/no withdrawal were obtained from 130 patients (63 females, 48%). RESULTS: The main finding was that reversible endocrine changes in sex steroid hormone levels could be observed in both sexes after withdrawal of AEDs. For CBZ, which was the drug used by the majority of the patients, withdrawal led to significant increases in serum testosterone concentrations and free androgen index (FAI) in both men (n = 19) and women (n = 19). Mean differences in change in FAI between the withdrawal group and nonwithdrawal group were in men 17.49 (CI 10.16-24.81, p 相似文献