癫痫患者更换抗癫痫药物后的预后分析:一项配对的前瞻性研究_Journal of Epilepsy

Authors：

JonMarc Finamore , MichaelR Sperling , ZhanTingting , 张颖颖 , 熊维希 , 慕洁

Corresponding author：

Keywords：

抗癫痫药物; 癫痫发作复发; 癫痫发作缓解

DOI：

10.7507/2096-0247.20170067

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一系列单队列研究已对癫痫患者更换抗癫痫药物(AEDs)预后进行了分析。研究以对照研究方式第一次探究了这个问题，针对服用所有类型的AEDs的控制不佳和癫痫无发作的癫痫患者，通过配对前瞻性研究方法对这些结果作进一步补充。研究回顾9个月内所有的门诊患者以确定单药治疗局灶性癫痫患者。并将更换AEDs的患者作为病例组，维持原来单药治疗方案作为对照组。分别针对发作现状(前6个月内是否有癫痫发作)、目前AEDs和控制不佳的AEDs数量对病例组和对照组进行配对，并在6个月后评估结果。病例组中癫痫无发作患者(n=12) 在6个月随访期间癫痫发作复发率为16.7%，对照组为2.8%(n=36，P=0.11)。病例组中控制不佳癫痫患者(n=27) 在6个月随访期癫痫发作缓解率为37%，对照组为55.6%(n=27，P=0.18)。控制不佳癫痫患者中治疗失败的药物在2种或2种以上的患者更不容易在6个月内达到病情缓解(P=0.057)。AEDs的药理机制和改变AEDs剂量均对癫痫预后无影响。研究进一步对癫痫无发作患者进行评估，更换药物的患者比维持原药物治疗患者癫痫发作的复发风险高14%。与维持原来药物方案相比，更换AEDs对控制不佳癫痫患者来说并不可能更易获得缓解，说明癫痫缓解是疾病的自发性改变，而非药物作用。

Citation： JonMarc Finamore, MichaelR Sperling, ZhanTingting, 张颖颖, 熊维希, 慕洁. 癫痫患者更换抗癫痫药物后的预后分析:一项配对的前瞻性研究. Journal of Epilepsy, 2017, 3(5): 423-429. doi: 10.7507/2096-0247.20170067 Copy

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2.	Kwan P, Brodie MJ, Kalviainen R, et al. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial.Lancet Neurol, 2011, 10(8): 881-890.
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5.	Callaghan BC, Anand K, Hesdorffer D, et al. Likelihood of seizure remission in an adult population with refractory epilepsy.Ann Neurol, 2007, 62(9): 382-389.
6.	Kwan P, Brodie MJ.Early identification of refractory epilepsy.N Engl J Med, 2000, 342(10): 314-319.
7.	Luciano AL, Shorvon SD.Results of treatment changes in patients with apparently drug-resistant chronic epilepsy.Ann Neurol, 2007, 62(2): 375-381.
8.	Schiller Y, Najjar Y.Quantifying the response to antiepileptic drugs: effect of past treatment history.Neurology, 2008, 70(1): 54-65.
9.	Mintzer S.Metabolic consequences of antiepileptic drugs.Curr Opin Neurol, 2010, 23(7): 164-169.
10.	Wang SP, Mintzer S, Skidmore CT, et al. Seizure recurrence and remission after switching antiepileptic drugs.Epilepsia, 2013, 54(6): 187-193.
11.	Goldenholz DM, Moss R, Scott J, et al. Confusing placebo effect with natural history in epilepsy: a big data approach.Ann Neurol, 2015, 78(3): 329-336.
12.	Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy.Neurology, 2012, 78(10): 1548-1554.
13.	Gilliam F.Optimizing health outcomes in active epilepsy.Neurology, 2002, 58(6): 9-20.
14.	Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed A novel assessment technique.JAMA, 1989, 261(11): 3273-3277.
15.	Harden CL, Meador KJ, Pennell PB, et al. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): Ⅱ.Teratogenesis and perinatal outcomes.Epilepsia, 2009, 50(8): 1237-1246.
16.	Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein.Ann Neurol, 2009, 65(6): 448-456.
17.	Chuang YC, Chuang HY, Lin TK, et al. Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis.Epilepsia, 2012, 53(2): 120-128.
18.	Morrell MJ, Hayes FJ, Sluss PM, et al. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine.Ann Neurol, 2008, 64(4): 200-211.
19.	Kwan P, Brodie MJ.Effectiveness of first antiepileptic drug.Epilepsia, 2001, 42(9): 1255-1260.

1. Brodie MJ, Chadwick DW, Anhut H, et al. Gabapentin versus lamotrigine monotherapy: a double-blind comparison in newly diagnosed epilepsy.Epilepsia, 2002, 43(5): 993-1000.
2. Kwan P, Brodie MJ, Kalviainen R, et al. Efficacy and safety of pregabalin versus lamotrigine in patients with newly diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group trial.Lancet Neurol, 2011, 10(8): 881-890.
3. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial.Lancet, 2007, 369(11): 1000-1015.
4. Baulac M, Brodie MJ, Patten A, et al. Efficacy and tolerability of zonisamide versus controlled-release carbamazepine for newly diagnosed partial epilepsy: a phase 3, randomised, double-blind, non-inferiority trial.Lancet Neurol, 2012, 11(6): 579-588.
5. Callaghan BC, Anand K, Hesdorffer D, et al. Likelihood of seizure remission in an adult population with refractory epilepsy.Ann Neurol, 2007, 62(9): 382-389.
6. Kwan P, Brodie MJ.Early identification of refractory epilepsy.N Engl J Med, 2000, 342(10): 314-319.
7. Luciano AL, Shorvon SD.Results of treatment changes in patients with apparently drug-resistant chronic epilepsy.Ann Neurol, 2007, 62(2): 375-381.
8. Schiller Y, Najjar Y.Quantifying the response to antiepileptic drugs: effect of past treatment history.Neurology, 2008, 70(1): 54-65.
9. Mintzer S.Metabolic consequences of antiepileptic drugs.Curr Opin Neurol, 2010, 23(7): 164-169.
10. Wang SP, Mintzer S, Skidmore CT, et al. Seizure recurrence and remission after switching antiepileptic drugs.Epilepsia, 2013, 54(6): 187-193.
11. Goldenholz DM, Moss R, Scott J, et al. Confusing placebo effect with natural history in epilepsy: a big data approach.Ann Neurol, 2015, 78(3): 329-336.
12. Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy.Neurology, 2012, 78(10): 1548-1554.
13. Gilliam F.Optimizing health outcomes in active epilepsy.Neurology, 2002, 58(6): 9-20.
14. Cramer JA, Mattson RH, Prevey ML, et al. How often is medication taken as prescribed A novel assessment technique.JAMA, 1989, 261(11): 3273-3277.
15. Harden CL, Meador KJ, Pennell PB, et al. Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): Ⅱ.Teratogenesis and perinatal outcomes.Epilepsia, 2009, 50(8): 1237-1246.
16. Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein.Ann Neurol, 2009, 65(6): 448-456.
17. Chuang YC, Chuang HY, Lin TK, et al. Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis.Epilepsia, 2012, 53(2): 120-128.
18. Morrell MJ, Hayes FJ, Sluss PM, et al. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine.Ann Neurol, 2008, 64(4): 200-211.
19. Kwan P, Brodie MJ.Effectiveness of first antiepileptic drug.Epilepsia, 2001, 42(9): 1255-1260.

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