Risks of seizure recurrence from antiepileptic drug withdrawal among seizure-free patients for more than three years_Journal of Epilepsy

Authors：

 QINJiaming ¹ , NIGuanzhong ¹ , FANGZiyan ² , CHENShuda ³ , CAIXiaodong ⁴ ,  ZHOULiemin ¹

1. Department of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510000, China;
2. Department of Neurology, Guangzhou brain hospital, Guangzhou 510000, China;
3. Department of Neurology, Guangzhou No.1 People's Hospital, Guangzhou 510000, China;
4. Department of Neurology, Epilepsy Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China;

Corresponding author：

ZHOULiemin, Email: lmzhou56@163.com

Keywords：

Epilepsy; Withdrawal; Relapse; Hippocampal sclerosis

DOI：

10.7507/2096-0247.20160036

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Objective To determine the outcome of antiepileptic drugs (AEDs) withdrawal in patients who had been seizure-free for more than two years. Methods Patients with epilepsy who had been seizure-free for at least two years and decided to stop AEDs therapy gradually were checked on every two months for seizure relapse. The inclusion criteria were:①diagnosis of epilepsy, defined as at least two unprovoked seizures at least 24 hours apart; ②patients remained seizure-free for at least 24 consecutive months during AEDs therapy; ③patients expressed a desire to discontinue AEDs therapy gradually and agreed to return for regular follow-ups; and④electroencephalogram (EEG) showed no epileptic discharge. The time to a seizure relapse and predictive factors were analyzed by survival methods, including sex; age at seizure onset; number of episodes; seizure-free period before AEDs withdrawal; duration of follow-up after AEDs withdrawal; AEDs tapering off period (taper period); results from brain MRI; EEG before seizure-free; EEG before drug withdrawal; seizure type (classified as generalized, partial, or multiple types based on history); the number of AEDs administered for long-term seizure control. A log-rank test was used for univariate analysis, and a Cox proportional hazard model was used for multivariate analysis. Results Sixty-eight patients (39 male, 29 female) were admithed. The relapsed rate was 23.5%. Univariate analysis and multivariate Cox regression analysis indicated that multiple AEDs, hippocampal sclerosis and withdrawal time were significantly correlated with seizure recurrence and those were significant independent predictive factors, with hazard ratio were 0.861, 2.223 and 2.137 respectively. Conclusions The relapsed rate in our study was similar to other studies. Distinguishing variables, such as multiple AEDs, hippocampal sclerosis and withdrawal time, need to be considered when decide to withdraw. Therefore, our recommendation is that after two years of being seizure-free, patients could consider withdrawal unless they are hippocampal sclerosis patients.

Citation： QINJiaming, NIGuanzhong, FANGZiyan, CHENShuda, CAIXiaodong, ZHOULiemin. Risks of seizure recurrence from antiepileptic drug withdrawal among seizure-free patients for more than three years. Journal of Epilepsy, 2016, 2(3): 193-198. doi: 10.7507/2096-0247.20160036 Copy

1.	Kaindl AM. Antiepileptic drugs and the developing brain. Cell Mol Life Sci, 2006, 63(4):399-413.
2.	Hessen E. Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing:results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia, 2006, 47(12):2038-2045.
3.	Loring DW, Medor KJ. Cognitive side effects of antiepileptic drugs in children. Neurology, 2004, 62(6):872-877.
4.	Shih JJ, Ochoa JG. A systematic review of antiepileptic drug initiation and withdrawal. Neurologist, 2009, 15(3):122-131.
5.	Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs:a meta-analysis. Neurology, 1994, 44(4):601-608.
6.	Verrotti A, Trotta D, Salladini C, et al. Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy. Ann Med, 2003, 35(3):207-215.
7.	Aktekin B. Withdrawal of antiepileptic drugs in adult patients free of seizures for 4 years:a prospective study. Epilepsy Behav, 2006, 8(3):616-619.
8.	Specchio LM, Tramacere L, La Neve A, et al. Discontinuing antiepileptic drugs in patients who are seizure free on. J Neurol Neurosurg Psychiatry, 2002, 72(1):22-25.
9.	Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients?. CNS Drugs, 2004, 18(4):201-212.
10.	Ohta H. Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic localization-related epilepsies. Brain and Development, 2004, 26(1):19-25.
11.	No authors listed. Practice parameter:guideline for discontinuing antiepileptic drugs in. Neurology, 1996, 47(2):600-602.
12.	No authors listed. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet, 1991, 337(8751):1175-1180.
13.	Cardoso TA, Coan AC, Kobayashi E, et al. Hippocampal abnormalities and seizure recurrence after antiepileptic drug. Neurology, 2006, 67(1):134-136.
14.	Strozzi I, Nolan SJ, Sperling MR, et al. Early versus late antiepileptic drug withdrawal for people with epilepsy in. Cochrane Database Syst Rev, 2015, 11(2):CD001902.
15.	Beghi E. Withdrawal of antiepileptic drugs:guidelines of the Italian League Against Epilepsy. Epilepsia, 2013, 54(Suppl 7):2-12.
16.	Berg AT, Shinnar S, Levy SR, et al. Two-year remission and subsequent relapse in children with newly diagnosed. Epilepsia, 2001, 42(12):1553-1562.
17.	Afshari D, Moradian N. Evaluating the rate of recurrence of epilepsy after therapy discontinuation in 2-year seizure-free epileptic patients. Int J Neurosci, 2012, 122(10):598-601.
18.	Incecik F, Herguner OM, Altunbasak SF, et al. Risk of recurrence after discontinuation of antiepileptic drug therapy in. J Pediatr Neurosci, 2014, 9(2):100-104.
19.	Li W. Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China. J Clin Neurosci, 2014, 21(6):997-1001.
20.	Pavlovic M, Jovic N, Pekmezovic T. Withdrawal of antiepileptic drugs in young patients with cryptogenic focal epilepsies. Seizure, 2012, 21(6):431-436.
21.	Su L. Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy. J Clin Neurosci, 2013, 20(6):790-794.
22.	Altunbaşak S, Artar O, Burgut RS, et al. Relapse risk analysis after drug withdrawal in epileptic children with. Seizure, 1999, 8(7):384-389.
23.	Cendes F. Epilepsies associated with hippocampal sclerosis. Acta Neuropathol, 2014, 128(1):21-37.
24.	潘光强, 易兴阳, 余昌明, 等.视频脑电图监测在抗癫痫药物治疗撤药中的意义.浙江医学, 2001, 23(9):565-566.
25.	Armijo JA, Adin J. Pharmacological basis for withdrawal of antiepileptic drugs. Rev Neurol, 2000, 30(4):336-350.

1. Kaindl AM. Antiepileptic drugs and the developing brain. Cell Mol Life Sci, 2006, 63(4):399-413.
2. Hessen E. Influence of major antiepileptic drugs on attention, reaction time, and speed of information processing:results from a randomized, double-blind, placebo-controlled withdrawal study of seizure-free epilepsy patients receiving monotherapy. Epilepsia, 2006, 47(12):2038-2045.
3. Loring DW, Medor KJ. Cognitive side effects of antiepileptic drugs in children. Neurology, 2004, 62(6):872-877.
4. Shih JJ, Ochoa JG. A systematic review of antiepileptic drug initiation and withdrawal. Neurologist, 2009, 15(3):122-131.
5. Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs:a meta-analysis. Neurology, 1994, 44(4):601-608.
6. Verrotti A, Trotta D, Salladini C, et al. Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy. Ann Med, 2003, 35(3):207-215.
7. Aktekin B. Withdrawal of antiepileptic drugs in adult patients free of seizures for 4 years:a prospective study. Epilepsy Behav, 2006, 8(3):616-619.
8. Specchio LM, Tramacere L, La Neve A, et al. Discontinuing antiepileptic drugs in patients who are seizure free on. J Neurol Neurosurg Psychiatry, 2002, 72(1):22-25.
9. Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients?. CNS Drugs, 2004, 18(4):201-212.
10. Ohta H. Prognosis after withdrawal of antiepileptic drugs in childhood-onset cryptogenic localization-related epilepsies. Brain and Development, 2004, 26(1):19-25.
11. No authors listed. Practice parameter:guideline for discontinuing antiepileptic drugs in. Neurology, 1996, 47(2):600-602.
12. No authors listed. Randomised study of antiepileptic drug withdrawal in patients in remission. Lancet, 1991, 337(8751):1175-1180.
13. Cardoso TA, Coan AC, Kobayashi E, et al. Hippocampal abnormalities and seizure recurrence after antiepileptic drug. Neurology, 2006, 67(1):134-136.
14. Strozzi I, Nolan SJ, Sperling MR, et al. Early versus late antiepileptic drug withdrawal for people with epilepsy in. Cochrane Database Syst Rev, 2015, 11(2):CD001902.
15. Beghi E. Withdrawal of antiepileptic drugs:guidelines of the Italian League Against Epilepsy. Epilepsia, 2013, 54(Suppl 7):2-12.
16. Berg AT, Shinnar S, Levy SR, et al. Two-year remission and subsequent relapse in children with newly diagnosed. Epilepsia, 2001, 42(12):1553-1562.
17. Afshari D, Moradian N. Evaluating the rate of recurrence of epilepsy after therapy discontinuation in 2-year seizure-free epileptic patients. Int J Neurosci, 2012, 122(10):598-601.
18. Incecik F, Herguner OM, Altunbasak SF, et al. Risk of recurrence after discontinuation of antiepileptic drug therapy in. J Pediatr Neurosci, 2014, 9(2):100-104.
19. Li W. Prospective study on the withdrawal and reinstitution of antiepileptic drugs among seizure-free patients in west China. J Clin Neurosci, 2014, 21(6):997-1001.
20. Pavlovic M, Jovic N, Pekmezovic T. Withdrawal of antiepileptic drugs in young patients with cryptogenic focal epilepsies. Seizure, 2012, 21(6):431-436.
21. Su L. Predictors for relapse after antiepileptic drug withdrawal in seizure-free patients with epilepsy. J Clin Neurosci, 2013, 20(6):790-794.
22. Altunbaşak S, Artar O, Burgut RS, et al. Relapse risk analysis after drug withdrawal in epileptic children with. Seizure, 1999, 8(7):384-389.
23. Cendes F. Epilepsies associated with hippocampal sclerosis. Acta Neuropathol, 2014, 128(1):21-37.
24. 潘光强, 易兴阳, 余昌明, 等.视频脑电图监测在抗癫痫药物治疗撤药中的意义.浙江医学, 2001, 23(9):565-566.
25. Armijo JA, Adin J. Pharmacological basis for withdrawal of antiepileptic drugs. Rev Neurol, 2000, 30(4):336-350.

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Risks of seizure recurrence from antiepileptic drug withdrawal among seizure-free patients for more than three years

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