唑尼沙胺添加治疗耐药性部分性癫痫有效性和安全性的Meta分析
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摘要
背景：癫痫是神经内科最常见的疾病之一。我国约有癫痫患者900万,患病率约为7‰。大部分癫痫患者通过自动缓解和抗癫痫药物(AEDs)治疗能够使发作得到控制,但仍有30%左右的患者发展成难治性癫痫。所谓难治是指癫痫患者对至少2种一线推荐、恰当使用、达到了有效血药浓度并可耐受的AEDs无反应,并且患者对癫痫发作的最低频率或缓解期的最长时间不满意。由于难治性癫痫患者控制不佳,比普通人存在更高的健康风险,也给医疗卫生体系和社会服务体系带来了巨大的挑战。因此,控制和预防癫痫的发作对于患者本身和社会都是有益的。
近二十年来,新的AEDs发展迅速,但难治性癫痫的控制仍然不能令人满意。唑尼沙胺是新型的AEDs,具有广谱的抗癫痫作用,已有多项临床试验证明唑尼沙胺添加治疗耐药性部分性癫痫发作有效,但各项研究纳入的样本量较少。我们收集此类临床试验,进行荟萃分析,以评估唑尼沙胺添加治疗耐药性部分性癫痫的有效性和安全性。
目的：采用Meta分析,评价唑尼沙胺添加治疗耐药性部分性癫痫的有效性和安全性。
方法：使用计算机检索PubMed、CENTRAL英文数据库以及CNKI、VIP、CBM中文数据库,时间不限；收集唑尼沙胺添加治疗耐药性部分性癫痫的临床试验。试验组接受唑尼沙胺添加治疗,对照组接受相应剂量的安慰剂添加治疗。对检索的文献进行评价,纳入符合要求的文献。结局指标为：有效率、退出率、不良反应发生率。数据处理应用Cochrane协作网提供的RevMan Manager5.1统计软件进行分析。各项指标采用总的优势比(OR)进行评估,设置95%的置信区间。
结果：共有7篇文章纳入本文的分析中。7项研究均为RCTs, Jadad质量评分为3-5分。共纳入1467名患者。结果显示：唑尼沙胺(100-600mg/d)添加治疗耐药性癫痫部分性发作有效,OR为2.40,95%CI(1.89,3.05),唑尼沙胺(300-600mg/d)添加治疗耐药性癫痫部分性发作有效,OR为2.46,95%CI(1.93,3.12)；唑尼沙胺(300-600mg/d)添加治疗耐药性癫痫复杂部分性发作有效,OR为3.07,95%CI(2.05,4.60)；唑尼沙胺较安慰剂有更明显的退出率,其中唑尼沙胺(100-600mg/d)较安慰剂组退出率的OR值为1.38,95%CI(1.01,1.89),唑尼沙胺(300-600mg/d)的OR值为1.55,95%CI(1.13,2.11)；唑尼沙胺添加治疗较安慰剂的明显不良反应为嗜睡和食欲下降,其OR值分别为1.49和2.97,95%C1分别为(1.01,2.20)和(1.78,4.96)。
结论：唑尼沙胺添加治疗耐药性部分性癫痫有效,添加治疗耐药性癫痫复杂部分性发作效果显著；较安慰剂有更高的退出率,短期耐受性较好,明显的不良反应为嗜睡和食欲下降。唑尼沙胺对患者生活质量的改善有待进一步研究；尚不能将此结论应用于唑尼沙胺的长期治疗及儿童癫痫患者中；唑尼沙胺对其他类型的癫痫发作和癫痫综合征的疗效尚不确切。
Background
The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to30%develop drug-resistant epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy.
Objective
To evaluate the efficacy and safety of zonisamide as an adjunctive treatment for people with drug-resistant partial epilepsy.
Search methods
We searched the English databases from PubMed, CENTRAL and the Chinese databases from CNKI, VIP, CBM. No time limit.
Selection criteria
Randomized placebo controlled adjunctive trials of zonisamide for people with drug-resistant partial epilepsy.
Data collection and analysis
We selected trials for inclusion and extracted data. Outcomes were:(1)50%or greater reduction in total seizure frequency;(2) treatment withdrawal;(3) adverse events. Summary odds ratio (OR) and95%confidence intervals(CIs) were estimated for each outcome.
Results
Seven trials (1467participants) were included. The overall OR with95%CI for50%reduction in seizure frequency compared to placebo for100to600mg/day of zonisamide was2.40(95%CI1.89to3.05). The OR for300to600mg/day of zonisamide was2.46(95%CI1.93to3.12). The OR for zonisamide (300to600mg per day) in people with complex epilepsy was3.07(95%CI2.05to4.60). The OR for treatment withdrawal for100to600mg/day zonisamide compared to placebo was1.38(95%CI1.01to1.89), and for300to600mg per day was1.55(95%CI1.13to2.11). The CIs of the following adverse effects indicate that they are significantly associated with zonisamide:somnolence1.49(95%CI1.01to2.20) and anorexia2.97(95%CI1.78to4.96).
Conclusion
Zonisamide has efficacy as an adjunctive treatment in people with drug-resistant partial epilepsy, especially in people with drug-resistant complex partial epilepsy. Patients are significantly more likely to withdraw from zonisamide than from placebo. The more frequent adverse effects are somnolence and anorexia in zonisamide than placebo. It's not sure if zonisamide has effects on patients' quality of life. The trials reviewed were of short duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.
近二十年来,新的AEDs发展迅速,但难治性癫痫的控制仍然不能令人满意。唑尼沙胺是新型的AEDs,具有广谱的抗癫痫作用,已有多项临床试验证明唑尼沙胺添加治疗耐药性部分性癫痫发作有效,但各项研究纳入的样本量较少。我们收集此类临床试验,进行荟萃分析,以评估唑尼沙胺添加治疗耐药性部分性癫痫的有效性和安全性。
目的：采用Meta分析,评价唑尼沙胺添加治疗耐药性部分性癫痫的有效性和安全性。
方法：使用计算机检索PubMed、CENTRAL英文数据库以及CNKI、VIP、CBM中文数据库,时间不限；收集唑尼沙胺添加治疗耐药性部分性癫痫的临床试验。试验组接受唑尼沙胺添加治疗,对照组接受相应剂量的安慰剂添加治疗。对检索的文献进行评价,纳入符合要求的文献。结局指标为：有效率、退出率、不良反应发生率。数据处理应用Cochrane协作网提供的RevMan Manager5.1统计软件进行分析。各项指标采用总的优势比(OR)进行评估,设置95%的置信区间。
结果：共有7篇文章纳入本文的分析中。7项研究均为RCTs, Jadad质量评分为3-5分。共纳入1467名患者。结果显示：唑尼沙胺(100-600mg/d)添加治疗耐药性癫痫部分性发作有效,OR为2.40,95%CI(1.89,3.05),唑尼沙胺(300-600mg/d)添加治疗耐药性癫痫部分性发作有效,OR为2.46,95%CI(1.93,3.12)；唑尼沙胺(300-600mg/d)添加治疗耐药性癫痫复杂部分性发作有效,OR为3.07,95%CI(2.05,4.60)；唑尼沙胺较安慰剂有更明显的退出率,其中唑尼沙胺(100-600mg/d)较安慰剂组退出率的OR值为1.38,95%CI(1.01,1.89),唑尼沙胺(300-600mg/d)的OR值为1.55,95%CI(1.13,2.11)；唑尼沙胺添加治疗较安慰剂的明显不良反应为嗜睡和食欲下降,其OR值分别为1.49和2.97,95%C1分别为(1.01,2.20)和(1.78,4.96)。
结论：唑尼沙胺添加治疗耐药性部分性癫痫有效,添加治疗耐药性癫痫复杂部分性发作效果显著；较安慰剂有更高的退出率,短期耐受性较好,明显的不良反应为嗜睡和食欲下降。唑尼沙胺对患者生活质量的改善有待进一步研究；尚不能将此结论应用于唑尼沙胺的长期治疗及儿童癫痫患者中；唑尼沙胺对其他类型的癫痫发作和癫痫综合征的疗效尚不确切。
Background
The majority of people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic agent, but up to30%develop drug-resistant epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding zonisamide, when used as an add-on treatment for drug-resistant partial epilepsy.
Objective
To evaluate the efficacy and safety of zonisamide as an adjunctive treatment for people with drug-resistant partial epilepsy.
Search methods
We searched the English databases from PubMed, CENTRAL and the Chinese databases from CNKI, VIP, CBM. No time limit.
Selection criteria
Randomized placebo controlled adjunctive trials of zonisamide for people with drug-resistant partial epilepsy.
Data collection and analysis
We selected trials for inclusion and extracted data. Outcomes were:(1)50%or greater reduction in total seizure frequency;(2) treatment withdrawal;(3) adverse events. Summary odds ratio (OR) and95%confidence intervals(CIs) were estimated for each outcome.
Results
Seven trials (1467participants) were included. The overall OR with95%CI for50%reduction in seizure frequency compared to placebo for100to600mg/day of zonisamide was2.40(95%CI1.89to3.05). The OR for300to600mg/day of zonisamide was2.46(95%CI1.93to3.12). The OR for zonisamide (300to600mg per day) in people with complex epilepsy was3.07(95%CI2.05to4.60). The OR for treatment withdrawal for100to600mg/day zonisamide compared to placebo was1.38(95%CI1.01to1.89), and for300to600mg per day was1.55(95%CI1.13to2.11). The CIs of the following adverse effects indicate that they are significantly associated with zonisamide:somnolence1.49(95%CI1.01to2.20) and anorexia2.97(95%CI1.78to4.96).
Conclusion
Zonisamide has efficacy as an adjunctive treatment in people with drug-resistant partial epilepsy, especially in people with drug-resistant complex partial epilepsy. Patients are significantly more likely to withdraw from zonisamide than from placebo. The more frequent adverse effects are somnolence and anorexia in zonisamide than placebo. It's not sure if zonisamide has effects on patients' quality of life. The trials reviewed were of short duration and results cannot be used to confirm longer periods of effectiveness in seizure control. The results cannot be extrapolated to monotherapy or to people with other seizure types or epilepsy syndromes.
引文
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[47]Chadwick DW, Marson AG Zonisamide add-on for drug-resistant partial epilepsy. The Cochrane Library 2009.
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