Efficacy of low to moderate doses of levetiracetam as initial monotherapy in adult patients with partial epilepsy_West China Medical Journal

Authors：

GUO Jianan , TIAN Linyu , LIU Wenyu , CHEN Jiani ,  ZHOU Dong

Departments of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

ZHOU Dong, Email: zhoudong66@yahoo.de

Keywords：

Levetiracetam; Partial epilepsy; Initial therapy; Seizure-free

DOI：

10.7507/1002-0179.201612181

Video：

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Objective To explore the efficacy of low to moderate doses of levetiracetam in adult patients with newly diagnosed partial epilepsy and possible predictors for poor treatment response. Methods We retrospectively analyzed the clinical data of patients treated in West China Hospital from March 2011 to December 2015 whose clinical data were input into the Epilepsy database. Patients with newly diagnosed partial epilepsy and whose initial anti-epileptic drug was levetiracetam were screened out for this study. Their clinical data, especially responses to the treatment of levetiracetam were reviewed. Results Ninety-six patients were included in this study. Seventy-one of them achieved seizure-free for a complete year after initial treatment of levetiracetam. Forty-eight patients (50.0%) achieved seizure-free with levetiracetam monotherapy; 23 patients (24.0%) achieved seizure-free for one year with levetiracetam combination therapy. Sixty-nine (97.2%) of the 71 patients achieved seizure-free with low to moderate doses of levetiracetam (500 to 1 500 mg/day), with or without combination of other antiepileptic drugs. High baseline seizure frequency before initial therapy was an independent predictor of poor levetiracetam response in this multivariate logistic regression mode (P=0.019). Conclusions Low to moderate levetiracetam is both effective and well tolerated in newly diagnosed partial epilepsy patients. High baseline seizure frequency before initial therapy is an independent predictor of poor levetiracetam response.

Citation： GUO Jianan, TIAN Linyu, LIU Wenyu, CHEN Jiani, ZHOU Dong. Efficacy of low to moderate doses of levetiracetam as initial monotherapy in adult patients with partial epilepsy. West China Medical Journal, 2017, 32(5): 643-648. doi: 10.7507/1002-0179.201612181 Copy

1.	Glauser T, Ben-Menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54(3): 551-563.
2.	Brodie MJ, Perucca E, Ryvlin P, et al. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology, 2007, 68(6): 402-408.
3.	Wright C, Downing J, Mungall D, et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol, 2013, 4(4): 192.
4.	Bodalia PN, Grosso AM, Sofat R, et al. Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials. Br J Clin Pharmacol, 2013, 76(5): 649-667.
5.	Pohlmann-Eden B, Marson AG, Noack-Rink M, et al. Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study. BMC Neurol, 2016, 16(1): 149.
6.	Snoeck E, Stockis A. Dose-response population analysis of levetiracetam add-on treatment in refractory epileptic patients with partial onset seizures. Epilepsy Res, 2007, 73(3): 284-291.
7.	Fang Y, Wu X, Xu L, et al. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. J Clin Neurosci, 2014, 21(1): 55-62.
8.	Tsai JJ, Yen DJ, Hsih MS, et al. Efficacy and safety of levetiracetam (up to 2000 mg/day) in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study. Epilepsia, 2006, 47(1): 72-81.
9.	Zou XM, Chen JN, An DM, et al. Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy. Seizure, 2015, 29(8): 81-85.
10.	Shih JJ, Whitlock JB, Chimato N, et al. Epilepsy treatment in adults and adolescents: expert opinion, 2016. Epilepsy Behav, 2017. (2017-02-22)[2017-04-18]. doi: 10.1016/j.yebeh.2016.11.018.
11.	Scott LJ. Lacosamide: a review in focal seizures in patients with epilepsy. Drugs, 2015, 75(18): 2143-2154.
12.	Perucca E, Dulac O, Shorvon S, et al. Harnessing the clinical potential of antiepileptic drug therapy: dosage optimisation. CNS Drugs, 2001, 15(8): 609-621.
13.	Brodie M, Barry SJ, Bamagous G, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
14.	Brodie MJ, Barry SJ, Bamagous GA. Effect of dosage failed of first antiepileptic drug on subsequent outcome. Epilepsia, 2013, 54(1): 194-198.
15.	Beghi E, Gatti G, Tonini C, et al. Adjunctive therapyversus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res, 2003, 57(1): 1-13.
16.	Perucca E. Overtreatment in epilepsy: adverse Consequences and mechanisms. Epilepsy Res, 2002, 52(1): 25-33.
17.	Ceylan M, Yalcin A, Bayraktutan OF, et al. Effects of levetiracetam monotherapy on sperm parameters and sex hormones: data from newly diagnosed patients with epilepsy. Seizure, 2016, 41: 70-74. doi: 10.1016/j.seizure.2016.06.001.
18.	Stephen LJ, Kelly K, Parker P, et al. Levetiracetam monotherapy--outcomes from an epilepsy clinic. Seizure, 2011, 20(7): 554-557.
19.	Kang BS, Moon HJ, Kim YS, et al. The long-term efficacy and safety of levetiracetam in a tertiary epilepsy centre. Epileptic Disord, 2013, 15(3): 302-310.
20.	Xiao Z, Li JM, Wang XF, et al. Efficacy and safety of levetiracetam (3, 000 mg/day) as an adjunctive therapy in Chinese patients with refractory partial seizures. Eur Neurol, 2009, 61(4): 233-239.
21.	Beran RG, Berkovic SF, Black AB, et al. Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory partial-onset seizures: a multicenter, open-label single-arm study. Epilepsy Res, 2005, 63(1): 1-9.
22.	Bhoi SK, Kalita J, Misra UK. Skin rash following levetiracetam. Seizure, 2016, 37: 45-47. doi: 10.1016/j.seizure.2016.02.014.
23.	Shahbaz N, Younus SM, Khan SA, et al. Levetiracetam induced increase in creatine phosphokinase levels. J Coll Physicians Surg Pak, 2017, 27(3): S63-s64.
24.	Alkhotani A, Mclachlan RS. Levetiracetam induced angioedema in a patient with previous anticonvulsant hypersensitivity reaction to phenytoin and lamotrigine. Seizure, 2012, 21(5): 407-408.
25.	Aikiä M, Kälviäinen R, Mervaala E, et al. Predictors of seizure outcome in newly diagnosed partial epilepsy: memory performance as a prognostic factor. Epilepsy Res, 1999, 37(2): 159-167.

1. Glauser T, Ben-Menachem E, Bourgeois B, et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia, 2013, 54(3): 551-563.
2. Brodie MJ, Perucca E, Ryvlin P, et al. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology, 2007, 68(6): 402-408.
3. Wright C, Downing J, Mungall D, et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol, 2013, 4(4): 192.
4. Bodalia PN, Grosso AM, Sofat R, et al. Comparative efficacy and tolerability of anti-epileptic drugs for refractory focal epilepsy: systematic review and network meta-analysis reveals the need for long term comparator trials. Br J Clin Pharmacol, 2013, 76(5): 649-667.
5. Pohlmann-Eden B, Marson AG, Noack-Rink M, et al. Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study. BMC Neurol, 2016, 16(1): 149.
6. Snoeck E, Stockis A. Dose-response population analysis of levetiracetam add-on treatment in refractory epileptic patients with partial onset seizures. Epilepsy Res, 2007, 73(3): 284-291.
7. Fang Y, Wu X, Xu L, et al. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types. J Clin Neurosci, 2014, 21(1): 55-62.
8. Tsai JJ, Yen DJ, Hsih MS, et al. Efficacy and safety of levetiracetam (up to 2000 mg/day) in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study. Epilepsia, 2006, 47(1): 72-81.
9. Zou XM, Chen JN, An DM, et al. Efficacy of low to moderate doses of oxcarbazepine in adult patients with newly diagnosed partial epilepsy. Seizure, 2015, 29(8): 81-85.
10. Shih JJ, Whitlock JB, Chimato N, et al. Epilepsy treatment in adults and adolescents: expert opinion, 2016. Epilepsy Behav, 2017. (2017-02-22)[2017-04-18]. doi: 10.1016/j.yebeh.2016.11.018.
11. Scott LJ. Lacosamide: a review in focal seizures in patients with epilepsy. Drugs, 2015, 75(18): 2143-2154.
12. Perucca E, Dulac O, Shorvon S, et al. Harnessing the clinical potential of antiepileptic drug therapy: dosage optimisation. CNS Drugs, 2001, 15(8): 609-621.
13. Brodie M, Barry SJ, Bamagous G, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
14. Brodie MJ, Barry SJ, Bamagous GA. Effect of dosage failed of first antiepileptic drug on subsequent outcome. Epilepsia, 2013, 54(1): 194-198.
15. Beghi E, Gatti G, Tonini C, et al. Adjunctive therapyversus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomised, pragmatic controlled trial. Epilepsy Res, 2003, 57(1): 1-13.
16. Perucca E. Overtreatment in epilepsy: adverse Consequences and mechanisms. Epilepsy Res, 2002, 52(1): 25-33.
17. Ceylan M, Yalcin A, Bayraktutan OF, et al. Effects of levetiracetam monotherapy on sperm parameters and sex hormones: data from newly diagnosed patients with epilepsy. Seizure, 2016, 41: 70-74. doi: 10.1016/j.seizure.2016.06.001.
18. Stephen LJ, Kelly K, Parker P, et al. Levetiracetam monotherapy--outcomes from an epilepsy clinic. Seizure, 2011, 20(7): 554-557.
19. Kang BS, Moon HJ, Kim YS, et al. The long-term efficacy and safety of levetiracetam in a tertiary epilepsy centre. Epileptic Disord, 2013, 15(3): 302-310.
20. Xiao Z, Li JM, Wang XF, et al. Efficacy and safety of levetiracetam (3, 000 mg/day) as an adjunctive therapy in Chinese patients with refractory partial seizures. Eur Neurol, 2009, 61(4): 233-239.
21. Beran RG, Berkovic SF, Black AB, et al. Efficacy and safety of levetiracetam 1000-3000 mg/day in patients with refractory partial-onset seizures: a multicenter, open-label single-arm study. Epilepsy Res, 2005, 63(1): 1-9.
22. Bhoi SK, Kalita J, Misra UK. Skin rash following levetiracetam. Seizure, 2016, 37: 45-47. doi: 10.1016/j.seizure.2016.02.014.
23. Shahbaz N, Younus SM, Khan SA, et al. Levetiracetam induced increase in creatine phosphokinase levels. J Coll Physicians Surg Pak, 2017, 27(3): S63-s64.
24. Alkhotani A, Mclachlan RS. Levetiracetam induced angioedema in a patient with previous anticonvulsant hypersensitivity reaction to phenytoin and lamotrigine. Seizure, 2012, 21(5): 407-408.
25. Aikiä M, Kälviäinen R, Mervaala E, et al. Predictors of seizure outcome in newly diagnosed partial epilepsy: memory performance as a prognostic factor. Epilepsy Res, 1999, 37(2): 159-167.

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Efficacy of low to moderate doses of levetiracetam as initial monotherapy in adult patients with partial epilepsy

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