拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展_Journal of Epilepsy

Authors：

渠蕊 ^1,2 ,  陈旭勤 ¹ , 戴园园 ²

1. ;
2. ;

Corresponding author：

陈旭勤, Email: xuqinlili@163.com

Keywords：

拉考沙胺; 吡仑帕奈; 单药治疗; 癫痫

DOI：

10.7507/2096-0247.20210057

Video：

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抗癫痫发作药物（Antiseizure medications，ASMs）在癫痫患者的治疗中起着重要的作用，因为大多数患者需要长期的抗惊厥治疗。由于高达 30% 的患者对药物治疗不耐受，因此需要选择新的治疗。单药治疗是新诊断癫痫治疗的金标准，如果第一次治疗不成功，可以选择第二次单药治疗。拉考沙胺（Lacosamide，LCM）和吡仑帕奈（Perampanel，PER）是第三代新型 ASMs，最新被批准用于局灶性癫痫的单药治疗。PER 对 α-氨基-3-羟基-5-甲基 4-异恶唑丙酸（AMPA）受体具有独特的和选择性的作用模式。LCM 通过选择性地增强电压门控钠通道的慢失活来发挥作用。文章对拉考沙胺和吡仑帕奈的作用机制、药物代谢动力学，以及作为单药治疗在癫痫患者中的有效性及安全性等方面作一综述，以期为临床医师提供用药参考，利于癫痫的个体化治疗。

Citation： 渠蕊, 陈旭勤, 戴园园. 拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展. Journal of Epilepsy, 2021, 7(4): 350-354. doi: 10.7507/2096-0247.20210057 Copy

1.	Baulac M, De Boer H, Elger C, et al. Epilepsy priorities in Europe: a report of the ILAE‐IBE epilepsy advocacy Europe task force. Epilepsia, 2015, 56(11): 1687-1695.
2.	Vossler DG, Weingarten M, Gidal BE, et al. Summary of antiepileptic drugs available in the United States of America. Epilepsy Curr, 2018, 18(4_suppl): 1-26.
3.	Brodie MJ, Barry SJE, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
4.	Tsai JJ, Wu T, Leung H, et al. Perampanel, an AMPA receptor antagonist: from clinical research to practice in clinical settings. Acta Neurol Scand, 2018, 137(4): 378-391.
5.	Johannessen Landmark C, Johannessen SI, Patsalos PN. Therapeutic drug monitoring of antiepileptic drugs: Current status and future prospects. Expert Opin Drug Metab Toxicol, 2020, 16(3): 227-238.
6.	Singh KP, Verma N. Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs. Pharmacol Rep, 2019, 71(3): 491-502.
7.	Santulli L, Coppola A, Balestrini S, et al. The challenges of treating epilepsy with 25 antiepileptic drugs. Pharmacol Res, 2016, 107: 211-219.
8.	Gschwind MA, Seeck M. Modern management of seizures and epilepsy. Swiss Med Wkly, 2016, 146: w14310.
9.	Brigo F. Lacosamide monotherapy for newly diagnosed epilepsy. Lancet Neurol, 2017, 16(1): 20-22.
10.	Mintzer S, French JA, Perucca E, et al. Is a separate monotherapy indication warranted for antiepileptic drugs? Lancet Neurol, 2015, 14(12): 1229-1240.
11.	Holtkamp D, Opitz T, Niespodziany I, et al. Activity of the anticonvulsant lacosamide in experimental and human epilepsy via selective effects on slow Na+ channel inactivation. Epilepsia, 2017, 58(1): 27-41.
12.	Wang X, Yu Y, Ma R, et al. Lacosamide modulates collapsin response mediator protein 2 and inhibits mossy fiber sprouting after kainic acid-induced status epilepticus. Neuroreport, 2018, 29(16): 1384-1390.
13.	凡振玉, 王天成. 拉考沙胺在老年癫痫患者中的应用进展. 癫痫杂志, 2021, 7(02): 147-151.
14.	Fukuyama K, Ueda Y, Okada M. Effects of Carbamazepine, Lacosamide and Zonisamide on Gliotransmitter Release Associated with Activated Astroglial Hemichannels. Pharmaceuticals, 2020, 13(6): 117.
15.	Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet, 2015, 54(9): 901-914.
16.	Hoy SM. Lacosamide: a review in focal-onset seizures in patients with epilepsy. CNS Drugs, 2018, 32(5): 473-484.
17.	Rosenow F, Brandt C, Bozorg A, et al. Lacosamide in patients with epilepsy of cerebrovascular etiology. Acta Neurol Scand, 2020, 141(6): 473-482.
18.	Liguori C, Izzi F, Manfredi N, et al. Lacosamide may improve cognition in patients with focal epilepsy: EpiTrack to compare cognitive side effects of lacosamide and carbamazepine. Epilepsy Behav Case Rep, 2018, 10: 35-37.
19.	Meschede C, Witt JA, Rademacher M, et al. Evaluating the longer-term cognitive effects of adjunctive perampanel compared to lacosamide in a naturalistic outpatient setting. Seizure, 2018, 58: 141-146.
20.	Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurol Scand, 2004, 110(4): 207-220.
21.	Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2017, 76: 24-31.
22.	Mintzer S, Dimova S, Zhang Y, et al. Effects of lacosamide and carbamazepine on lipids in a randomized trial. Epilepsia, 2020, 61(12): 2696-2704.
23.	Matsudaira T, Terada T, Araki Y, et al. HyperCKemia associated with lacosamide therapy in an elderly patient with focal onset epilepsy. Seizure-Eur J Epilep, 2018, 63: 14-16.
24.	Gupta SS, Patti R, Lindsay D, et al. Lacosamide: Associated Hyponatremia. Am J Ther, 2018, 25(6): e729-e730.
25.	Simko J, Fekete S, Malakova J, et al. The effect of lacosamide on bone tissue in orchidectomised male albino Wistar rats. Biomed Pap, 2015, 159(3): 394-399.
26.	Corbellini ÁB, Torre PP, Hristova VN, et al. Cardioembolic acute cerebral micro‐infarcts in the context of atrial fibrillation after low‐dose intravenous infusion of lacosamide. Epileptic Disord, 2020, 22(1): 83-89.
27.	Lachuer C, Corny J, Bézie Y, et al. Complete atrioventricular block in an elderly patient treated with low-dose lacosamide. Cardiovasc Toxicol, 2018, 18(6): 579-582.
28.	Ng PC, Schimmel J, Wang GS. Lacosamide overdose: a case of QRS prolongation and seizure. J Emerg Med, 2019, 56(6): 652-656.
29.	Berei TJ, Lillyblad MP, Almquist AK. Lacosamide-induced recurrent ventricular tachycardia in the acute care setting. J Pharm Pract, 2018, 31(2): 222-226.
30.	Potschka H, Trinka E. Perampanel: Does it have broad‐spectrum potential? Epilepsia, 2019, 60: 22-36.
31.	Yamamoto Y, Shiratani Y, Asai S, et al. Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy. Seizure, 2020, 83: 181-186.
32.	Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: a novel noncompetitive AMPA receptor antagonist. Epilepsia, 2015, 56(1): 12-27.
33.	Steinhoff BJ, Ben‐Menachem E, Ryvlin P, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia, 2013, 54(8): 1481-1489.
34.	Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
35.	Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(8): 1252-1263.
36.	Meador KJ, Yang H, Piña‐Garza JE, et al. Cognitive effects of adjunctive perampanel for partial‐onset seizures: a randomized trial. Epilepsia, 2016, 57(2): 243-251.
37.	褚思嘉, 汤继宏. 第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展. 癫痫杂志, 2021, 7(01): 58-61.
38.	Wechsler RT, Li G, French J, et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical‐controlled, multicenter, double‐blind study. Epilepsia, 2014, 55(7): 1088-1098.
39.	Lattanzi S, Cagnetti C, Foschi N, et al. Lacosamide monotherapy for partial onset seizures. Seizure, 2015, 27: 71-74.
40.	Giráldez BG, Toledano R, García-Morales I, et al. Long-term efficacy and safety of lacosamide monotherapy in the treatment of partial-onset seizures: a multicenter evaluation. Seizure, 2015, 29: 119-122.
41.	Baulac M, Rosenow F, Toledo M, et al. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol, 2017, 16(1): 43-54.
42.	Kwan P, Mintzer S, Laurenza A, et al. Evaluation of perampanel as monotherapy for focal seizures: experience from open-label extension studies. Epilepsy Behav Case Rep, 2018, 9: 1-5.
43.	Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal‐onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open‐label Study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
44.	Maloney E, McGinty RN, Costello DJ. Real world experience with lacosamide monotherapy-a single center 1-year follow-up study. Epilepsy Res, 2018, 142: 16-19.
45.	Zawar I, Franic L, Knight EP. Response to lacosamide monotherapy in a patient with medically refractory Jeavons syndrome: a case report and review of the literature. Epileptic Disord, 2020, 22(5): 643-647.
46.	Zhao T, Li H, Ma L, et al. Safety, efficacy, and tolerability of lacosamide for the treatment of epilepsy in pediatric patients in Uygur, China. Epilepsy Behav, 2021, 117: 107814.
47.	Dirani M, Nasreddine W, Abdulla F, et al. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy Behav Case Rep, 2014, 2: 164-166.
48.	Toledano Delgado R, García‐Morales I, Parejo‐Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic‐clonic seizures: Experience from a national multicenter registry. Epilepsia, 2020, 61(6): 1109-1119.
49.	Gil-Nagel A, Burd S, Toledo M, et al. A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy. Seizure, 2018, 54: 61-66.
50.	Jaramillo JA, María JCE, Úbeda JMG, et al. Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON). Epilepsy Behav, 2020, 102: 106655.
51.	Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.

1. Baulac M, De Boer H, Elger C, et al. Epilepsy priorities in Europe: a report of the ILAE‐IBE epilepsy advocacy Europe task force. Epilepsia, 2015, 56(11): 1687-1695.
2. Vossler DG, Weingarten M, Gidal BE, et al. Summary of antiepileptic drugs available in the United States of America. Epilepsy Curr, 2018, 18(4_suppl): 1-26.
3. Brodie MJ, Barry SJE, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology, 2012, 78(20): 1548-1554.
4. Tsai JJ, Wu T, Leung H, et al. Perampanel, an AMPA receptor antagonist: from clinical research to practice in clinical settings. Acta Neurol Scand, 2018, 137(4): 378-391.
5. Johannessen Landmark C, Johannessen SI, Patsalos PN. Therapeutic drug monitoring of antiepileptic drugs: Current status and future prospects. Expert Opin Drug Metab Toxicol, 2020, 16(3): 227-238.
6. Singh KP, Verma N. Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs. Pharmacol Rep, 2019, 71(3): 491-502.
7. Santulli L, Coppola A, Balestrini S, et al. The challenges of treating epilepsy with 25 antiepileptic drugs. Pharmacol Res, 2016, 107: 211-219.
8. Gschwind MA, Seeck M. Modern management of seizures and epilepsy. Swiss Med Wkly, 2016, 146: w14310.
9. Brigo F. Lacosamide monotherapy for newly diagnosed epilepsy. Lancet Neurol, 2017, 16(1): 20-22.
10. Mintzer S, French JA, Perucca E, et al. Is a separate monotherapy indication warranted for antiepileptic drugs? Lancet Neurol, 2015, 14(12): 1229-1240.
11. Holtkamp D, Opitz T, Niespodziany I, et al. Activity of the anticonvulsant lacosamide in experimental and human epilepsy via selective effects on slow Na+ channel inactivation. Epilepsia, 2017, 58(1): 27-41.
12. Wang X, Yu Y, Ma R, et al. Lacosamide modulates collapsin response mediator protein 2 and inhibits mossy fiber sprouting after kainic acid-induced status epilepticus. Neuroreport, 2018, 29(16): 1384-1390.
13. 凡振玉, 王天成. 拉考沙胺在老年癫痫患者中的应用进展. 癫痫杂志, 2021, 7(02): 147-151.
14. Fukuyama K, Ueda Y, Okada M. Effects of Carbamazepine, Lacosamide and Zonisamide on Gliotransmitter Release Associated with Activated Astroglial Hemichannels. Pharmaceuticals, 2020, 13(6): 117.
15. Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet, 2015, 54(9): 901-914.
16. Hoy SM. Lacosamide: a review in focal-onset seizures in patients with epilepsy. CNS Drugs, 2018, 32(5): 473-484.
17. Rosenow F, Brandt C, Bozorg A, et al. Lacosamide in patients with epilepsy of cerebrovascular etiology. Acta Neurol Scand, 2020, 141(6): 473-482.
18. Liguori C, Izzi F, Manfredi N, et al. Lacosamide may improve cognition in patients with focal epilepsy: EpiTrack to compare cognitive side effects of lacosamide and carbamazepine. Epilepsy Behav Case Rep, 2018, 10: 35-37.
19. Meschede C, Witt JA, Rademacher M, et al. Evaluating the longer-term cognitive effects of adjunctive perampanel compared to lacosamide in a naturalistic outpatient setting. Seizure, 2018, 58: 141-146.
20. Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of epilepsy. Acta Neurol Scand, 2004, 110(4): 207-220.
21. Chen B, Choi H, Hirsch LJ, et al. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav, 2017, 76: 24-31.
22. Mintzer S, Dimova S, Zhang Y, et al. Effects of lacosamide and carbamazepine on lipids in a randomized trial. Epilepsia, 2020, 61(12): 2696-2704.
23. Matsudaira T, Terada T, Araki Y, et al. HyperCKemia associated with lacosamide therapy in an elderly patient with focal onset epilepsy. Seizure-Eur J Epilep, 2018, 63: 14-16.
24. Gupta SS, Patti R, Lindsay D, et al. Lacosamide: Associated Hyponatremia. Am J Ther, 2018, 25(6): e729-e730.
25. Simko J, Fekete S, Malakova J, et al. The effect of lacosamide on bone tissue in orchidectomised male albino Wistar rats. Biomed Pap, 2015, 159(3): 394-399.
26. Corbellini ÁB, Torre PP, Hristova VN, et al. Cardioembolic acute cerebral micro‐infarcts in the context of atrial fibrillation after low‐dose intravenous infusion of lacosamide. Epileptic Disord, 2020, 22(1): 83-89.
27. Lachuer C, Corny J, Bézie Y, et al. Complete atrioventricular block in an elderly patient treated with low-dose lacosamide. Cardiovasc Toxicol, 2018, 18(6): 579-582.
28. Ng PC, Schimmel J, Wang GS. Lacosamide overdose: a case of QRS prolongation and seizure. J Emerg Med, 2019, 56(6): 652-656.
29. Berei TJ, Lillyblad MP, Almquist AK. Lacosamide-induced recurrent ventricular tachycardia in the acute care setting. J Pharm Pract, 2018, 31(2): 222-226.
30. Potschka H, Trinka E. Perampanel: Does it have broad‐spectrum potential? Epilepsia, 2019, 60: 22-36.
31. Yamamoto Y, Shiratani Y, Asai S, et al. Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy. Seizure, 2020, 83: 181-186.
32. Patsalos PN. The clinical pharmacology profile of the new antiepileptic drug perampanel: a novel noncompetitive AMPA receptor antagonist. Epilepsia, 2015, 56(1): 12-27.
33. Steinhoff BJ, Ben‐Menachem E, Ryvlin P, et al. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia, 2013, 54(8): 1481-1489.
34. Brodie MJ, Stephen LJ. Prospective audit with adjunctive perampanel: preliminary observations in focal epilepsy. Epilepsy Behav, 2016, 54: 100-103.
35. Ettinger AB, LoPresti A, Yang H, et al. Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel. Epilepsia, 2015, 56(8): 1252-1263.
36. Meador KJ, Yang H, Piña‐Garza JE, et al. Cognitive effects of adjunctive perampanel for partial‐onset seizures: a randomized trial. Epilepsia, 2016, 57(2): 243-251.
37. 褚思嘉, 汤继宏. 第三代新型抗癫痫药吡仑帕奈在癫痫治疗中的研究进展. 癫痫杂志, 2021, 7(01): 58-61.
38. Wechsler RT, Li G, French J, et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: results from a historical‐controlled, multicenter, double‐blind study. Epilepsia, 2014, 55(7): 1088-1098.
39. Lattanzi S, Cagnetti C, Foschi N, et al. Lacosamide monotherapy for partial onset seizures. Seizure, 2015, 27: 71-74.
40. Giráldez BG, Toledano R, García-Morales I, et al. Long-term efficacy and safety of lacosamide monotherapy in the treatment of partial-onset seizures: a multicenter evaluation. Seizure, 2015, 29: 119-122.
41. Baulac M, Rosenow F, Toledo M, et al. Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled-release carbamazepine in patients with newly diagnosed epilepsy: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Neurol, 2017, 16(1): 43-54.
42. Kwan P, Mintzer S, Laurenza A, et al. Evaluation of perampanel as monotherapy for focal seizures: experience from open-label extension studies. Epilepsy Behav Case Rep, 2018, 9: 1-5.
43. Yamamoto T, Lim SC, Ninomiya H, et al. Efficacy and safety of perampanel monotherapy in patients with focal‐onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open‐label Study 342 (FREEDOM Study). Epilepsia Open, 2020, 5(2): 274-284.
44. Maloney E, McGinty RN, Costello DJ. Real world experience with lacosamide monotherapy-a single center 1-year follow-up study. Epilepsy Res, 2018, 142: 16-19.
45. Zawar I, Franic L, Knight EP. Response to lacosamide monotherapy in a patient with medically refractory Jeavons syndrome: a case report and review of the literature. Epileptic Disord, 2020, 22(5): 643-647.
46. Zhao T, Li H, Ma L, et al. Safety, efficacy, and tolerability of lacosamide for the treatment of epilepsy in pediatric patients in Uygur, China. Epilepsy Behav, 2021, 117: 107814.
47. Dirani M, Nasreddine W, Abdulla F, et al. Seizure control and improvement of neurological dysfunction in Lafora disease with perampanel. Epilepsy Behav Case Rep, 2014, 2: 164-166.
48. Toledano Delgado R, García‐Morales I, Parejo‐Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic‐clonic seizures: Experience from a national multicenter registry. Epilepsia, 2020, 61(6): 1109-1119.
49. Gil-Nagel A, Burd S, Toledo M, et al. A retrospective, multicentre study of perampanel given as monotherapy in routine clinical care in people with epilepsy. Seizure, 2018, 54: 61-66.
50. Jaramillo JA, María JCE, Úbeda JMG, et al. Effectiveness and safety of perampanel as early add-on treatment in patients with epilepsy and focal seizures in the routine clinical practice: Spain prospective study (PERADON). Epilepsy Behav, 2020, 102: 106655.
51. Villanueva V, Montoya J, Castillo A, et al. Perampanel in routine clinical use in idiopathic generalized epilepsy: The 12‐month GENERAL study. Epilepsia, 2018, 59(9): 1740-1752.

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拉考沙胺和吡仑帕奈单药治疗癫痫的研究进展

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