Effectiveness and Safety of Flunarizine for Refractory Epilepsy: A Meta-Analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 ZHAO Changbao , ZHANG Jianbin , REN Xu , WANG Sufang , YUAN Zhijun , LI Xiaohui , DONG Hongyan , LIU Hanrui , HU Xiaoyan , DUAN Shengjie

Affiliated Heji Hospital of Changzhi Medical Collage, Changzhi 046000, China;

Corresponding author：

ZHAO Changbao, Email: ya1013@126.com

Keywords：

Flunarizine; Refractory epilepsy; Meta-analysis; Systematic review

DOI：

10.7507/1672-2531.20100613

Video：

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Objective 　To assess the effectiveness and safety of flunarizine for refractory epilepsy.
Methods 　Relevant randomized controlled trials (RCTs) were searched from the database of PubMed, EMbase, Cochrane Library, CNKI, CBM, and VIP, and the related references were traced to obtain the information. The methodological quality of included RCTs was assessed using Jadad scale and meta-analysis was performed using RevMan 5.0 software.
Results 　A total of eight studies involving 545 patients were included. The results of meta-analyses showed that: based on the conventional therapy, compared with placebo and none-treatment, flunarizine was more effective on adults and children with refractory epilepsy (OR=2.98, 95%CI 1.88 to -4.73; OR=33.75, 95%CI 4.13 to -276.00). Major adverse events of flunarizine were fatigue, dizziness, headache, and weight gain etc. All those symptoms except for the weight gain were observed in the early stage of medication, which might get self-cured or could disappear by constant medication or reducing the dose or symptomatic treatment.
Conclusion 　The present study shows that based on the conventional therapy, flunarizine is effective and safe for refractory epilepsy.

Citation： ZHAO Changbao,ZHANG Jianbin,REN Xu,WANG Sufang,YUAN Zhijun,LI Xiaohui,DONG Hongyan,LIU Hanrui,HU Xiaoyan,DUAN Shengjie. Effectiveness and Safety of Flunarizine for Refractory Epilepsy: A Meta-Analysis. Chinese Journal of Evidence-Based Medicine, 2010, 10(12): 1461-1466. doi: 10.7507/1672-2531.20100613 Copy

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2.	Reynolds Eh, LAE/BE/WHO Global Campaign “Out of the Shadows”: global and regional developments. Epilepsia, 2001, 42(8): 1094-1100.
3.	Scott RA, Lhatoo SD, Sander JW. The treatment of epilepsy in developing countries: where do we go from here? BullWorld Health Organ, 2001, 79(4): 344-351.
4.	George B, Kularni SK, Mathur R. Motor and electrographic response of refractory experimental status in rats and effect of calcium channel blockers. Indian J Exp Biol, 2000, 38: 105-112.
5.	Joseph S, David J, Joseph T. Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice. Indian J Physiol Pharmacol, 1998, 42: 383-388.
6.	Hoppu K, Nergardh AR, Eriksson AS, et al. Flunarizine of limited value in children with intractable epilepsy. Pediatr Neurol, 1995, 13: 143-147.
7.	Chaisewikul R, Baillie N, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev, 2001; 4: CD002750.
8.	Pledger GW, Sackellares JC, Treiman DM, et al. Flunarizine for treatment of partial seizures of a concentration-controlled trial. Neurology, 1994, 44(10): 1830-1836.
9.	Sarreveld E, de Beukelaar F, Wilson AF, et al. Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy. Can J Neurol Sci, 1989, 16: 187-190.
10.	吴逊, 沈鼎烈. 难治性癫痫. 中华神经科杂志, 1998, 31(1): 4.
11.	Jadad AR. Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary. Control Clin Trials, 1996, 17: 1-12.
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14.	林忠荣, 陈利广, 张爱娇. 西比灵辅助治疗癫痫28例. 福建医药杂志, 2003: 25(3): 89-90.
15.	周胜华, 周辉飞, 冯耀耀. 氟桂利嗪添加治疗难治性癫痫的临床研究. 全科医学临床与教育, 2008, 6(3): 183-184, 187.
16.	徐修森, 金红, 胡小红, 等. 盐酸氟桂嗪附加抗痫药治疗难治性癫痫58例. 人民军医, 1994, (9): 42-43.
17.	王学峰, 晏勇, 吕洋. 氟桂利嗪抗癫痫及逆转难治性癫痫病人多药耐受基因的表达. 中国新药与临床杂志, 2001, 20(05): 363-365.
18.	王清峰, 孙顺昌, 胡新建, 等. 西比灵辅助治疗癫痫的疗效及其对脑脊液钙含量的影响. 临床神经病学杂志, 2002, 15(5): 305-306.
19.	Pledger GW, Treiman DM. Design of an individualized fixed-dose clinical trial to test the antiepileptic efficacy of a plasma flunarizine concentration. Control Clin Trials, 1991, 12(6): 768-79.
20.	Cerghino JJ. Flunarizine. In: Engel J, Pedley TA, eds. Epilepsy: a comprehensive textbook. Philadelpia: Lippincott-Raven, 1997, 1515-1519.
21.	Treiman D, Pledger G, DeGiorgio I, et al. A rising plasma concentration tolerability study of flunarizine in comedicated epileptic patients. Epilepsia, 1993, 34: 944-953.
22.	马仁飞, 周本秀, 扬毅, 等. 盐酸氟桂利嗪剂量递增法治疗难治性癫痫部分性发作的疗效观察. 中华神经科杂志, 2001, 34(1): 32-35.

1. 林庆. 实用小儿癫癎病学. 北京: 北京科学技术出版社, 2004: 5.
2. Reynolds Eh, LAE/BE/WHO Global Campaign “Out of the Shadows”: global and regional developments. Epilepsia, 2001, 42(8): 1094-1100.
3. Scott RA, Lhatoo SD, Sander JW. The treatment of epilepsy in developing countries: where do we go from here? BullWorld Health Organ, 2001, 79(4): 344-351.
4. George B, Kularni SK, Mathur R. Motor and electrographic response of refractory experimental status in rats and effect of calcium channel blockers. Indian J Exp Biol, 2000, 38: 105-112.
5. Joseph S, David J, Joseph T. Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice. Indian J Physiol Pharmacol, 1998, 42: 383-388.
6. Hoppu K, Nergardh AR, Eriksson AS, et al. Flunarizine of limited value in children with intractable epilepsy. Pediatr Neurol, 1995, 13: 143-147.
7. Chaisewikul R, Baillie N, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy. Cochrane Database Syst Rev, 2001; 4: CD002750.
8. Pledger GW, Sackellares JC, Treiman DM, et al. Flunarizine for treatment of partial seizures of a concentration-controlled trial. Neurology, 1994, 44(10): 1830-1836.
9. Sarreveld E, de Beukelaar F, Wilson AF, et al. Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy. Can J Neurol Sci, 1989, 16: 187-190.
10. 吴逊, 沈鼎烈. 难治性癫痫. 中华神经科杂志, 1998, 31(1): 4.
11. Jadad AR. Moore A, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary. Control Clin Trials, 1996, 17: 1-12.
12. 李保敏, 于臻, 张冬青, 等. 多药耐药基因在小儿难治性癫痫外周血中的表达及氟桂利嗪对其表达的逆转作用. 山东大学学报(医学版), 2009, 47(4): 30-32, 37.
13. 庞学民, 姚伟明, 林旭. 西比灵治疗癫痫的临床研究[J].河南实用神经疾病杂志, 2000, 3(3): 5-7.
14. 林忠荣, 陈利广, 张爱娇. 西比灵辅助治疗癫痫28例. 福建医药杂志, 2003: 25(3): 89-90.
15. 周胜华, 周辉飞, 冯耀耀. 氟桂利嗪添加治疗难治性癫痫的临床研究. 全科医学临床与教育, 2008, 6(3): 183-184, 187.
16. 徐修森, 金红, 胡小红, 等. 盐酸氟桂嗪附加抗痫药治疗难治性癫痫58例. 人民军医, 1994, (9): 42-43.
17. 王学峰, 晏勇, 吕洋. 氟桂利嗪抗癫痫及逆转难治性癫痫病人多药耐受基因的表达. 中国新药与临床杂志, 2001, 20(05): 363-365.
18. 王清峰, 孙顺昌, 胡新建, 等. 西比灵辅助治疗癫痫的疗效及其对脑脊液钙含量的影响. 临床神经病学杂志, 2002, 15(5): 305-306.
19. Pledger GW, Treiman DM. Design of an individualized fixed-dose clinical trial to test the antiepileptic efficacy of a plasma flunarizine concentration. Control Clin Trials, 1991, 12(6): 768-79.
20. Cerghino JJ. Flunarizine. In: Engel J, Pedley TA, eds. Epilepsy: a comprehensive textbook. Philadelpia: Lippincott-Raven, 1997, 1515-1519.
21. Treiman D, Pledger G, DeGiorgio I, et al. A rising plasma concentration tolerability study of flunarizine in comedicated epileptic patients. Epilepsia, 1993, 34: 944-953.
22. 马仁飞, 周本秀, 扬毅, 等. 盐酸氟桂利嗪剂量递增法治疗难治性癫痫部分性发作的疗效观察. 中华神经科杂志, 2001, 34(1): 32-35.

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Effectiveness and Safety of Flunarizine for Refractory Epilepsy: A Meta-Analysis

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