Levetiracetam – clinical position Review article
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Published:
Sep 30, 2014
Keywords:
epilepsy, levetiracetam, monotherapy, adjunctive therapy
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Abstract
Approximately 30% of patients with epilepsy do not experience satisfactory seizure control with antiepileptic drug monotherapy and often require polytherapy. Levetiracetam (LEV, [S]-α-ethyl-2-oxo-1-pyrrolidine acetamide) is a novel antiepileptic drug that is indicated for clinical use as adjunctive therapy to treat patients with intractable partia-onset seizures with or without secondary generalization. The drug appears to have a broad spectrum of activity in that it is effective against juvenile myoclonic epilepsy; tonic-clonic, absence and myoclonic epilepsy, photosensitive epilepsy, as well as atypical absence or atonic seizures. Furthermore, increasing evidence suggests significant efficacy in children aged 10 years and younger with partial onset seizures and in those with myoclonic seizures. Levetiracetam is so efficacious as monotherapy that patients with refractory partial epilepsy can be successfully converted to monotherapy. Additionally, levetiracetam has been successfully used as a first-line drug to treat newly diagnosed patients with epilepsy.
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References
1. Lynch BA, Lambeng N, Nocka K et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 2004; 101: 9861-9866.
2. Wright C, Downing J, Mungall D et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol 2013 Dec 4; 4:192.
3. Carreno M. Levetiracetam. Drugs Today (Barc) 2007; 43(11): 769-794.
4. Bialer M. Clinical pharmacology of parental use of antiepileptic drugs. Epilepsia 2007; 48 (suppl. 8): 46-48.
5. Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia 2001; 42:1255-1260.
6. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2004; 45(5): 410-423.
7. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of new onset epilepsy. Raport of the Therapeutics and Technology Assessment Subcommittee, Quality Standarts Subcommittee of American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62: 1252-1260.
8. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of refractory epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standarts Subcommittee of American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62: 1261-1273.
9. Cereghino JJ, Biton V, Abou-Khalil B et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 2000; 55: 236-242.
10. Brodie et al: Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68; 402-408.
11. Sirven JI, Drazkowski JF. Levetiracetam. [W]: The treatment of epilepsy – Principles & Practice, Wyllie E. Lippincott Williams & Wilkins 2006.
12. Luszczki JJ, Andres MM, Czuczwar P et al. Pharmacodynamic and pharmacokinetic charakterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis. Epilepsia 2006; 47(1): 10-20.
13. Luszczki JJ, Andres MM, Czuczwar P et al. Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice. Eur Neuropsychopharmacol 2005; 15(6): 609-616.
14. Taubol E, Gregoraszczuk EL, Tworzydo A et al. Comparison of reproductive effects of levetiracetam and valproate studies in prepubertal porcine ovarian follicular cells. Epilepsia 2006; 47(9): 1580-1583.
15. Patsalos PN, Froscher W, Pisani F, van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia 2002; 43: 365-385.
16. Coupez R, Nicolas JM, Browne TR. Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Epilepsia 2003; 44(2): 171-178.
17. Bauer J. Encephalopathy induced by levetiracetam added to valproate. Acta Neurol Scand 2007; 12: 123-130.
18. Livoti P, Falla M, Pro S et al. Effect of Levetiracetam on EEGs: an Inspective and Quantative Stusy in Patient with Epilepsy. Materiały zjazdowe 2005.
19. Patel DK, Andriola MR, Bhachawat RK et al. Efficacy of Levetiracetam to normalize EEG in patient with primary generalized epilepsy. Materiały zjazdowe 2006.
20. Tilz C, Stefan H, Hopfengaertner R et al. Influenze of Levetiracetam on ictal and postictal EEG in patients with partial seizures. Eur J Neurol 2006; 13: 1352-1358.
21. Grupa badawcza EURAP. Opanowanie i leczenie napadów padaczkowych w czasie ciąży. Obserwacje pochodzące z rejestru EURAP dotyczącego kobiet w ciąży chorych na padaczkę. Neurology 2006; 66: 354-360.
22. Boylan LS, Flint LA, Labovitz DL et al. Depression but not seizure frequency predicts quality of life treatment-resistant epilepsy. Neurology 2004; 62(2): 258-261.
23. Bird JM, Joseph ZA. Levetiracetam in clinical use – a prospective observational study. Seizure 2003; 12: 613-616.
24. Krishnamoorthy ES, Trimble MR. Forced normalisation: clinical and therapeutic relevance. Epilepsia 1999; 40 (suppl. 10): 57-64.
25. Majkowski J. Psychoza schizofrenopodobna z wymuszoną normalizacją EEG u chorej z odogniskową padaczką w przebiegu leczenia LEV. Epileptologia 2005; 13: 57-69.
26. Motamedi M, Ngyyen DK, Zaatren M et al. Levetiracetam efficacy in refractory partial-onset seizures, especially after failed epilepsy surgery. Epilepsia 2003; 44: 211-214.
27. Martien KM. Levetiracetam utility in autistic children limited by behavioural side effects. Epilepsia 2003; 44(9): 238.
28. Nakken KO, Eriksson AS, Loussius R, Johanessen SI. A paradoxal effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
29. Gustafson MC, Ritter FJ, Frost MD et al. Behavioral and emotional effects of levetiracetam in children with intractable epilepsy. Epilepsia 2002; 43(7): 58-59.
30. Kaufman KR: Monotherapy treatment of bipolar disorder with levetiracetam. Epilepsy Behav 2004; 5: 1017-1020.
31. Weintraub D, Buchsbaum R, Resor SR Jr, Hirsch LJ. Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav 2007; 10(1): 105-110.
32. Bilo L, Meo R, Fulvia de Leva M. Levetiracetam in idiopathic generalized epilepsy and porphyria cutanea tarda. Clin Drug Investig 2006; 26: 357-359.
33. Paul F, Meencke HJ. Levetiracetam in focal epilepsy and hepatic porphyria: a case report. Epilepsia 2004; 45(5): 559-560.
34. Zaatreh MM. Levetiracetam in porphyric status epilepticus: a case report. Clin Neuropharmacol 2005; 28(5): 243-244.
35. Oulis P, Karapoulios E, Masdrakis VG et al. Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome. World J Biol Psychiatry 2008; 9(1): 76-77.
36. Awaad Y, Michon AM, Minarik S et al. Use of levetiracetam to treat tics in children and adolescents with Tourette syndrome. Mov Disord 2005; 20(6): 714-718.
37. Smith-Hicks CL, Bridges DD, Paynter NP et al. A double blind randomized placebo control trial of levetiracetam in Tourette syndrome. Mov Disord 2007; 22(12): 1764-1770.
38. Deleu D. Levetiracetam in the treatment of idiopathic hemifacial spasm. Neurology 2004; 62(11): 2134-2135.
39. Yardimci N, Karatas M, Kilinc M et al. Levetiracetam in Meige’s syndrome. Acta Neurol Scand 2006 ; 114(1): 63-66.
40. Hawker K, Frohman E, Racke M. Levetiracetam for phasic spasticity in multiple sclerosis. Arch Neurol 2003 Dec; 60(12): 1772-1774.
2. Wright C, Downing J, Mungall D et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol 2013 Dec 4; 4:192.
3. Carreno M. Levetiracetam. Drugs Today (Barc) 2007; 43(11): 769-794.
4. Bialer M. Clinical pharmacology of parental use of antiepileptic drugs. Epilepsia 2007; 48 (suppl. 8): 46-48.
5. Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia 2001; 42:1255-1260.
6. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2004; 45(5): 410-423.
7. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of new onset epilepsy. Raport of the Therapeutics and Technology Assessment Subcommittee, Quality Standarts Subcommittee of American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62: 1252-1260.
8. French JA, Kanner AM, Bautista J et al. Efficacy and tolerability of the new antiepileptic drugs. [W]: Treatment of refractory epilepsy. Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standarts Subcommittee of American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62: 1261-1273.
9. Cereghino JJ, Biton V, Abou-Khalil B et al. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 2000; 55: 236-242.
10. Brodie et al: Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology 2007; 68; 402-408.
11. Sirven JI, Drazkowski JF. Levetiracetam. [W]: The treatment of epilepsy – Principles & Practice, Wyllie E. Lippincott Williams & Wilkins 2006.
12. Luszczki JJ, Andres MM, Czuczwar P et al. Pharmacodynamic and pharmacokinetic charakterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis. Epilepsia 2006; 47(1): 10-20.
13. Luszczki JJ, Andres MM, Czuczwar P et al. Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice. Eur Neuropsychopharmacol 2005; 15(6): 609-616.
14. Taubol E, Gregoraszczuk EL, Tworzydo A et al. Comparison of reproductive effects of levetiracetam and valproate studies in prepubertal porcine ovarian follicular cells. Epilepsia 2006; 47(9): 1580-1583.
15. Patsalos PN, Froscher W, Pisani F, van Rijn CM. The importance of drug interactions in epilepsy therapy. Epilepsia 2002; 43: 365-385.
16. Coupez R, Nicolas JM, Browne TR. Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Epilepsia 2003; 44(2): 171-178.
17. Bauer J. Encephalopathy induced by levetiracetam added to valproate. Acta Neurol Scand 2007; 12: 123-130.
18. Livoti P, Falla M, Pro S et al. Effect of Levetiracetam on EEGs: an Inspective and Quantative Stusy in Patient with Epilepsy. Materiały zjazdowe 2005.
19. Patel DK, Andriola MR, Bhachawat RK et al. Efficacy of Levetiracetam to normalize EEG in patient with primary generalized epilepsy. Materiały zjazdowe 2006.
20. Tilz C, Stefan H, Hopfengaertner R et al. Influenze of Levetiracetam on ictal and postictal EEG in patients with partial seizures. Eur J Neurol 2006; 13: 1352-1358.
21. Grupa badawcza EURAP. Opanowanie i leczenie napadów padaczkowych w czasie ciąży. Obserwacje pochodzące z rejestru EURAP dotyczącego kobiet w ciąży chorych na padaczkę. Neurology 2006; 66: 354-360.
22. Boylan LS, Flint LA, Labovitz DL et al. Depression but not seizure frequency predicts quality of life treatment-resistant epilepsy. Neurology 2004; 62(2): 258-261.
23. Bird JM, Joseph ZA. Levetiracetam in clinical use – a prospective observational study. Seizure 2003; 12: 613-616.
24. Krishnamoorthy ES, Trimble MR. Forced normalisation: clinical and therapeutic relevance. Epilepsia 1999; 40 (suppl. 10): 57-64.
25. Majkowski J. Psychoza schizofrenopodobna z wymuszoną normalizacją EEG u chorej z odogniskową padaczką w przebiegu leczenia LEV. Epileptologia 2005; 13: 57-69.
26. Motamedi M, Ngyyen DK, Zaatren M et al. Levetiracetam efficacy in refractory partial-onset seizures, especially after failed epilepsy surgery. Epilepsia 2003; 44: 211-214.
27. Martien KM. Levetiracetam utility in autistic children limited by behavioural side effects. Epilepsia 2003; 44(9): 238.
28. Nakken KO, Eriksson AS, Loussius R, Johanessen SI. A paradoxal effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
29. Gustafson MC, Ritter FJ, Frost MD et al. Behavioral and emotional effects of levetiracetam in children with intractable epilepsy. Epilepsia 2002; 43(7): 58-59.
30. Kaufman KR: Monotherapy treatment of bipolar disorder with levetiracetam. Epilepsy Behav 2004; 5: 1017-1020.
31. Weintraub D, Buchsbaum R, Resor SR Jr, Hirsch LJ. Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav 2007; 10(1): 105-110.
32. Bilo L, Meo R, Fulvia de Leva M. Levetiracetam in idiopathic generalized epilepsy and porphyria cutanea tarda. Clin Drug Investig 2006; 26: 357-359.
33. Paul F, Meencke HJ. Levetiracetam in focal epilepsy and hepatic porphyria: a case report. Epilepsia 2004; 45(5): 559-560.
34. Zaatreh MM. Levetiracetam in porphyric status epilepticus: a case report. Clin Neuropharmacol 2005; 28(5): 243-244.
35. Oulis P, Karapoulios E, Masdrakis VG et al. Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome. World J Biol Psychiatry 2008; 9(1): 76-77.
36. Awaad Y, Michon AM, Minarik S et al. Use of levetiracetam to treat tics in children and adolescents with Tourette syndrome. Mov Disord 2005; 20(6): 714-718.
37. Smith-Hicks CL, Bridges DD, Paynter NP et al. A double blind randomized placebo control trial of levetiracetam in Tourette syndrome. Mov Disord 2007; 22(12): 1764-1770.
38. Deleu D. Levetiracetam in the treatment of idiopathic hemifacial spasm. Neurology 2004; 62(11): 2134-2135.
39. Yardimci N, Karatas M, Kilinc M et al. Levetiracetam in Meige’s syndrome. Acta Neurol Scand 2006 ; 114(1): 63-66.
40. Hawker K, Frohman E, Racke M. Levetiracetam for phasic spasticity in multiple sclerosis. Arch Neurol 2003 Dec; 60(12): 1772-1774.