Source: https://www.epilepsia.su/jour/article/view/410
Timestamp: 2019-04-19 02:59:34+00:00

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Aim – to elucidate the role of antiepileptic pharmacotherapy in pathomorphosis of focal epilepsy in adult patients.
Materials and methods. We examined 91 patients with focal epilepsy (main group, G); among them, 37 (41%) men (M) and 54 (59%) women (W). At the time of the first visit, 82 (90%) of them [33 (89%) M and 49 (91%) W] were under antiepileptic therapy. The age of patients ranged from 18 to 78 years (average 37.5 years). The debut of epilepsy was observed at the ages from 4 to 71 years. The duration of the disease ranged from 1 to 52 years, with the average of 16.1 years. All patients were then followed up for 1 to 2.5 years. Clinical and neurological examinations were conducted in all patients; laboratory and instrumental diagnostic tests were used if indicated. The medical history of patients was analyzed from the onset of epilepsy; if needed, new therapies were prescribed or the existing therapies were modified. The therapeutic efficacy was assessed using the data from the daily-seizures diary. The differences between the groups were tested for their significance using the Chi-square test or the exact Fisher test if there were less than five observations in the group.
Results. Only 47 (52%) patients of group G [21 (57%) M and 26 (48%) W] received an antiepileptic therapy from the debut of the disease; the therapy was then adjusted in 41 (45%) cases [19 (51%) M and 22 (41%) W (р>0.05)]. Of the 82 patients receiving therapy at the time of examination, 37 (45%) received the basic, 20 (24%) – the updated, and 24 (29%) – a combination of the basic and updated AED; in about 2% of cases, a combination with the 1st generation drugs was prescribed. Monotherapy was used in 45 (55%), and polytherapy – in 37 (45%) patients. Of the 19 patients taking KBZ as the starting monotherapy, 10 (52%) received the drug in the non-prolonged form, twice a day. Relapse after long-term remission (12 months or more) in 80% of cases was associated with changes in the AED regimen. Side effects were observed in 43 (52%) patients under the treatment [15 (45%) M and 28 (57%) W]. Among those, who underwent MRI examination, structural epileptogenic changes were detected in 37 (54%) patients [21 (72%) M and 16 (40%) W (p<0.05)]. Comorbidity and the associated co-therapy were detected in 88% M and 90% W who were >50 years old.
Conclusion. Antiepileptic pharmacotherapy is a leading factor that induces evolutionary changes in the clinical and neurophysiological picture of epilepsy. With a timely and rational approach, the use of AED allows for creating favorable development of pathomorphosis of the disease. Full patients awareness of the AED therapeutic regimens and the associated risks may increases the compliance, reduce the risk of decompensation and improve the prognosis of epilepsy.
1. Brodie M. J. Pharmacological Treatment of Drug-Resistant Epilepsy in Adults: a Practical Guide. Curr Neurol Neurosci Rep. 2016 Sep; 16 (9): 82. DOI: 10.1007/s11910-016-0678-x.
2. Rudakova I. G. RMZh (in Russian). 2014; 22 (16): 1147-1150.
3. Mar’enko L. B. Zhurnal nevrologii i psihiatrii im. S. S. Korsakova. (in Russian). 2014; 114 (4): 18-22.
4. Kalinin V. A. Modeling the pathogenesis of epilepsy in different age groups based on the results of visual evoked potentials of the brain on the reversed chess pattern. Problems of equipment and technologies of telecommunications. Proceedings of the XIV International scientific and technical conference [Modelirovanie patogeneza epilepsii v razlichnyh vozrastnyh gruppah po rezul’tatam zritel’nyh vyzvannyh potencialov golovnogo mozga na obrashhenniy shahmatniy pattern/Problemy tekhniki i tekhnologiy telekommunikaciy. Materialy XIV Mezhdunarodnoy nauchno- tekhnicheskoy konferencii (in Russian)]. Samara. 2013; 562-565.
5. Tovaralieva G. F. Epilepsy disease and approaches to its treatment. In the collection: the Intellectual potential of the XXI century. Materials of the International (correspondence) scientific-practical conference. Scientific (non- periodic) electronic publication. Under the General editorship of A. I. Vostretsov [Zabolevanie epilepsiey i podhody k ee lecheniyu. V sbornike: Intellektual’niy potencial XXI veka. Materialy Mezhdunarodnoy (zaochnoy) nauchno-prakticheskoy konferencii. Nauchnoe (neperiodicheskoe) elektronnoe izdanie. Pod obshhey redakciey A. I. Vostrecova (in Russian)]. 2016; 175-182.
6. Avakyan G. N., Blinov D. V., Lebedeva A. V., Burd S. G., Avakyan G. G. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian)]. 2017; 9 (1): 6-25. DOI: 10.17749/2077-8333.2017.9.1.006-025.
7. Bjørk M. H., Veiby G., Reiter S. C., Berle J. O., Daltveit A. K., Spigset O., Engelsen B. A., Gilhus N. E. Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective populationbased cohort study on frequency, risk factors, medication, and prognosis. Epilepsia. 2015 Jan; 56 (1): 28- 39. DOI: 10.1111/epi.12884. Epub 2014 Dec 19. PMID: 25524160.
8. Tilz C. Epilepsy in the elderly. Special clinical features and treatment strategies. Internist (Berl). 2014 Jul; 55 (7): 782-8. doi : 10.1007/s00108-014- 3467-0. PMID: 24969607.
9. Karlov V. A. Epilepsy in children and adult women and men: A guide for doctors [Epilepsiya u detey i vzroslyh zhenshhin i muzhchin: Rukovodstvo dlya vrachey (in Russian)]. Moscow. 2010; 720 s.
10. Oishi M. Differential diagnosis of epilepsy. Nihon Rinsho. 2014 May; 72 (5): 839-44. Review. Japanese. PMID: 24912284.
11. Boutros N. N., Gjini K., Moran J., Chugani H., Bowyer S. Panic versus epilepsy: a challenging differential diagnosis. Clin EEG Neurosci. 2013 Oct; 44 (4): 313-8. DOI: 10.1177/1550059413478163. Epub 2013 Apr 12. PMID: 23585641.
13. Zenkov L. R. Epilepsy: diagnosis and treatment. Guide for doctors [Epilepsiya: diagnoz i lechenie. Rukovodstvo dlya vrachey (in Russian)]. Moscow. 2012.
14. Avakyan G. N. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian)]. 2014; 6 (4): 46-49.
15. Muhin K. Yu., Pylaeva O. A., Gluhova L. Yu., Mironov M. B., Bobylova M. Yu. Russkiy zhurnal detskoy nevrologii (in Russian). 2014; 4: 30-49.
16. Di Bonaventura C., Labate A., Maschio M., Meletti S., Russo E. AMPA receptors and Perampanel behind selected epilepsies: current evidence and future perspectives.
17. Expert Opin Pharmacother. 2017 Oct 12. DOI: 10.1080/14656566.2017.1392509. [Epub ahead of print] PMID: 29023170.
18. Vlasov P. N. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian)]. 2015; 7 (4): 40-49.
19. Abou-Khalil BW. Antiepileptic Drugs. Continuum (Minneap Minn). 2016 Feb; 22 (1 Epilepsy): 132-56. DOI: 10.1212/CON.0000000000000289. Review. PMID: 26844734.
20. Burd S. G. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian)]. 2013; 5 (2): 50-51.
21. Freitas-Lima P., Alexandre V. Jr., Pereira L. R., Feletti F., Perucca E., Sakamoto A. C. Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy. Epilepsy Res. 2011 Mar; 94 (1-2): 117-20. DOI: 10.1016/j.eplepsyres.2011.01.007. Epub 2011 Feb 1. PMID: 21282041.
22. Anderson G. D., Saneto R. P. Modified-Release Formulations of Second-Generation Antiepileptic Drugs: Pharmacokinetic and Clinical Aspects. CNS Drugs. 2015 Aug; 29 (8): 669-81. DOI: 10.1007/s40263-015-0268-5. Review. PMID: 26369919.
23. Avakyan G. N., Burd S. G. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian)]. 2012; 4 (2): 67-71.
24. Lalic M., Cvejic J., Popovic J., Bozic K., Golocorbin-Kon S., Al-Salami H., Mikov M. Lamotrigine and valproate pharmacokinetics interactions in epileptic patients. Eur J Drug Metab Pharmacokinet. 2009 Apr-Jun; 34 (2): 93-9. PMID: 19645218.
25. Eadie M. J. Treating epilepsy in pregnant women. Expert Opin Pharmacother. 2014 Apr; 15 (6): 841-50. DOI: 10.1517/14656566.2014.896902. Epub 2014 Mar 10. Review. PMID: 24611535.
26. Rudakova I. G. Modern strategy and tactics of treatment of epilepsy in adults. Textbook [Sovremennaya strategiya i taktika lecheniya epilepsii u vzroslyh. Uchebnoe posobie (in Russian)]. Moscow. 2013.
27. Davidson L., Derry C. Seizure classification key to epilepsy management. Practitioner. 2015 Sep; 259 (1785): 13-9, 2. Review. PMID: 26591652.
28. Broun T., Holms G. Epilepsy. Clinical guideline [Epilepsiya. Klinicheskoe rukovodstvo (in Russian)]. Moscow. 2014.
29. Lawn N., Chan J., Lee J., Dunne J. Is the first seizure epilepsy--and when? Epilepsia. 2015 Sep; 56 (9): 1425-31. DOI: 10.1111/epi.13093. Epub 2015 Jul 27. PMID: 26222507.
31. various forms of epilepsy. PhD diss. [Paradoksal’nye effekty antiepilepticheskih preparatov pri lechenii razlichnyh form epilepsii. Diss. …kand. med. nauk (in Russian)]. Moscow. 2011.
32. Karpova V. I., Pylaeva O. A., Muhin K. Yu., Petruhin A. C. Russkiy zhurnal detskoy nevrologii (in Russian). 2011; 6 (3): 36-46.
33. Abou-Khalil B. Selecting Rational Drug Combinations in Epilepsy. CNS Drugs. 2017 Oct 3. DOI: 10.1007/s40263-017-0471-7. [Epub ahead of print] PMID: 28975553.
34. Kotov A. S., Tolstova N. V. Klinicheskaya nevrologiya (in Russian). 2010; 1: 17-21.
35. Pasternak E., Alyautdin R., Asetskaya I., Lepakhin V., Romanov B., Merculov V. Safety and efficacy of valproic acid preparations. Int J Risk Saf Med. 2015; 27 Suppl 1: 31-2. DOI: 10.3233/JRS-150679. PMID: 26639699.
36. Berg M., Welty T. E., Gidal B. E., Diaz F. J., Prebill R., Szaflarski J. P., Dworetzky B. A., Pollard J. R., Elder E. J. Jr., Jiang W., Jiang X., Switzer R. D., Privitera M. D. Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy: The EQUIGEN Randomized Clinical Trial. JAMA Neurol. 2017 Aug 1; 74 (8): 919-926. DOI: 10.1001/jamaneurol.2017.0497. PMID: 28654954.
37. Gagne J. J., Kesselheim A. S., Choudhry N. K., Polinski J. M., Hutchins D., Matlin O. S., Brennan T. A., Avorn J., Shrank W. H. Comparative effectiveness of generic versus brand-name antiepileptic medications. Epilepsy Behav. 2015 Nov; 52 (Pt A): 14-8. DOI: 10.1016/j.yebeh.2015.08.014. Epub 2015 Sep 19. PMID: 26386779.
38. Groth A., Wilke T., Borghs S., Gille P., Joeres L. Real life pharmaceutical treatment patterns for adult patients with focal epilepsy in Germany: a longitudinal and cross-sectional analysis of recently approved anti-epileptic drugs. Ger Med Sci.
39. 2017 Jun 12; 15: Doc09. DOI: 10.3205/000250. eCollection 2017. PMID: 28638313.
40. Kotov A. S. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2014; 6 (3): 58.
41. Kotov A. S. Zhurnal nevrologii i psihiatrii im. C. C. Korsakova (in Russian). 2010; 110 (11): 46-48.
42. Smithson W. H., Hukins D., Buelow J. M., Allgar V., Dickson J. Adherence to medicines and self-management of epilepsy: a community-based study. Epilepsy Behav. 2013 Jan; 26 (1): 109-13. DOI: 10.1016/j.yebeh.2012.10.021. Epub 2012 Dec 14. PMID: 23246201.
43. López González F. J., Rodríguez Osorio X., Gil-Nagel Rein A., Carreño Martínez M., Serratosa Fernández J., Villanueva Haba V., Donaire Pedraza A. J., Mercadé Cerdá J. M. Drug-resistant epilepsy: definition and treatment alternatives. Neurologia. 2015 Sep; 30 (7): 439-46. DOI: 10.1016/j.nrl.2014.04.012. Epub 2014 Jun 26. English, Spanish. PMID: 24975343.
44. Medel-Matus J. S., Reynolds A., Shin D., Sankar R., Mazarati A. Regulation of kindling epileptogenesis by hippocampal Toll-like receptors 2. Epilepsia. 2017 Jun 20. DOI: 10.1111/epi.13826.
45. Rudakova I. G., Belova Yu. A., Kotov A. S. Farmakorezistentnaya epilepsiya poddaetsya lecheniyu. Vestnik epileptologii (in Russian). 2013; 1: 3-7.
46. Rudakova I. G. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2014; 6 (4): 62-66.
47. Badalyan O. L. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions. (in Russian). 2011; 3 (4): 50-51.
48. Kotov A. S. Nevrologiya i psihiatriya (in Russian). 2014; 32-36.
49. Sørensen A. T., Kokaia M. Novel approaches to epilepsy treatment. Epilepsia. 2013 Jan; 54 (1): 1-10. DOI: 10.1111/epi.12000. Epub 2012 Oct 25. Review. PMID: 23106744.
50. Kovaleva I. Yu. Epilepsiya i paroksizmal’nye sostoyaniya / Epilepsy and paroxysmal conditions (in Russian). 2017; 9 (1): 51-61. DOI: 10.17749/2077-8333.2017.9.1.051-061.
51. Gaitatzis A., Sander J. W. The long-term safety of antiepileptic drugs. CNS Drugs. 2013 Jun; 27 (6): 435-55. DOI: 10.1007/s40263-013-0063-0. Review. PMID: 23673774.
52. Thomson C. Monitoring side effects of antiepileptic drugs. Vet Rec. 2014 Sep 13; 175 (10): 245-6. DOI: 10.1136/vr.g5438. No abstract available. Erratum in: Vet Rec. 2014 Sep 27; 175 (12): 301. PMID: 25217601.
53. Bjørk M. H., Veiby G., Reiter S. C., Berle J.Ø, Daltveit A. K., Spigset O., Engelsen B. A., Gilhus N. E. Depression and anxiety in women with epilepsy during pregnancy and after delivery: a prospective populationbased cohort study on frequency, risk factors, medication, and prognosis. Epilepsia. 2015 Jan; 56 (1): 28- 39. DOI: 10.1111/epi.12884. Epub 2014 Dec 19. PMID: 25524160.
54. Kotov A. S. Annaly klinicheskoy i eksperimental’noy nevrologii (in Russian). 2010; 4 (3): 10-13.
55. Dmitrenko D. V., Shnayder N. A., Govorina Yu. B., Murav’eva A. V. Nevrologiya, neyropsihiatriya, psihosomatika (in Russian). 2015; 7 (3): 15-20.
57. recommendation. Epilepsy Behav. 2015 Mar; 44: 151-4. DOI: 10.1016/j.yebeh. 2014. 12.039. Epub 2015 Feb 20. PMID: 25705826.
58. Hao N., Jiang H., Wu M., Pan T., Yan B., Liu J., Mu J., Liu W., Li J., O\’Brien T.J., Chen Z., Vajda F., Zhou D. Breastfeeding initiation, duration and exclusivity in mothers with epilepsy from South West China. Epilepsy Res. 2017 Sep; 135: 168- 175. DOI: 10.1016/j.eplepsyres.2017.06.015. Epub 2017 Jun 30. PMID: 28709079.
59. Sveinsson O., Tomson T. Epilepsy and menopause: potential implications for pharmacotherapy. Drugs Aging. 2014 Sep; 31 (9): 671-5. DOI: 10.1007/s40266-014-0201-5. Review. PMID: 25079452.
60. Dussault P. M., Lazzari A. A. Epilepsy and osteoporosis risk. Curr Opin Endocrinol Diabetes Obes. 2017 Dec; 24 (6): 395-401. DOI: 10.1097/MED.0000000000000366. PMID: 28857845.
61. Petty S. J., Wilding H., Wark J. D. Osteoporosis Associated with Epilepsy and the Use of Anti-Epileptics-a Review. Curr Osteoporos Rep. 2016 Apr; 14 (2): 54-65. DOI: 10.1007/s11914-016-0302-7. Review. PMID: 26879819.
62. Kotov A. S., Rudakova I. G. Zh Nevrol Psikhiatr Im S. S. Korsakova (in Russian).2011; 111 (7): 4-7. PMID: 21947064.
63. Bruun E., Virta L. J., Kälviäinen R., Keränen T. Choice of the first anti- epileptic drug in elderly patients with newly diagnosed epilepsy: A Finnish retrospective study. Seizure. 2015 Sep; 31: 27-32. DOI: 10.1016/j.seizure.2015.06.016. Epub 2015 Jul 4. PMID: 26362374.

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