Gender characteristics of therapy for genetic generalized epilepsy in adults

Valproate is generally the drug of choice in genetic generalized epilepsy (GGE). But its therapy was changed after the appearance of the 2015 International League against Epilepsy (ILAE) recommendations to limit the dose of valproates in women.
Objective: to assess the spectrum of antiepileptic drugs (AEDs) and to evaluate the efficiency of therapy in adults with GGE, in terms of the gender characteristics of the latter and the ILAE recommendations.
Patients and methods. A retrospective open-label observational study was conducted. A cohort of patients was formed according to their visits to physicians in 2013 to 2017. Two patient groups were identified. Group 1 included 80 patients (35 males, 45 females); their mean age was 27.1±3.6 years; they were followed in 2013–2014. Group 2 consisted of 137 patients (53 males, 84 females); their mean age was 29.4±4.6 years; they visited their physicians in 2015–2017. The spectrum of AEDs that were used in monotherapy or polytherapy was assessed. The efficiency of therapy was determined by the onset of remission.
Results and discussion. The patients of the two groups were matched for the spectrum of GGE syndromes. Most patients received valproates; more than 35% took levetiracetam; lamotrigine was used slightly less often. In Group 2, females used polytherapy more frequently than males (p=0.03). The percentage of achievement of clinical and encephalographic remission (CER) was higher in Group 2 (p=0.05); there was no significant difference in this indicator between men and women in the two groups. In Group 2, among those achieving CER, the percentage of
patients receiving monotherapy decreased and that of those having polytherapy increased (p=0.02). The spectrum of AEDs used to achieve CEP
remained unchanged in both groups; however, there was a significant difference in the drug dosing regimens.
Conclusion. Current therapy for GGE is successful and leads to remission in most patients. After 2015, dual therapy for GGE is used significantly
more often in women than in men (p<0.05). The combination of valproate with levetiracetam or lamotrigine predominates.

genetic generalized epilepsy, monotherapy, polytherapy, gender characteristics

1. Yacubian EM, de Araujo Filho GM. Management issues for patients with idiopathic generalized epilepsies. Epileptology. 2013 Mar; 1(1):1-10.

2. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010 Apr; 51(4):676-85. doi: 10.1111/j.1528-1167.2010.02522.x. Epub 2010 Feb 26.

3. French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015 Sep 15;85(11):950-7.

4. Tomson T, Marson A, Boon P, et al. Valproate in the treatment of epilepsy in women and girls. Pre-Publication Summary of Recommendations from a joint Task Force of ILAE-Commission on European Affairs and European Academy of Neurology (EAN). 2015. https://www.eaneurology.org/fileadmin/_migrated/content_uploads/ValproateCommentILAE-0315.pdf

5. Gesche J, Khanevski M, Solberg C, et al. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies. Epilepsia. 2017 Apr;58(4):e64-e69. doi: 10.1111/epi.13702. Epub 2017 Feb 23.

6. Mukhin KYu, Petrukhin AS. Idiopaticheskie formy epilepsii: sistematika, diagnostika, terapiya [Idiopathic forms of epilepsy: systematics, diagnostics, therapy]. Moscow: Art-Biznes-Tsentr; 2000. 19 p.

7. Karlov VA, Gekht AB, Guzeva VI, et al. Algorithms of mono - and polytherapy in clinical epileptology. Part 1. General principles for selection of pharmacotherapy. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2016;116(6):109-14. (In Russ.)

8. Callaghan B, Schlesinger M, Rodemer W, et al. Remission and relapse in a drug-resistant epilepsy population followed prospectively. Epilepsia. 2011 Mar;52(3):619-26. doi: 10.1111/j.1528-1167.2010.02929.x. Epub 2011 Jan 26.

9. Vlasov PN. Use of valproates in women of childbearing age and pregnant women with epilepsy. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2015;7(1S): 4-9. (In Russ.). doi: 10.14412/2074-2711-2015-1S-4-9

10. Benbadis SR. Practical management issues for idiopathic generalized epilepsies. Epilepsia. 2005;46 Suppl 9:125-32.

11. Nevitt SJ, Sudell M, Weston J, et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2017 Dec 15;12:CD011412. doi: 10.1002/14651858.CD011412.pub3.

12. Coppola G, Auricchio G, Federico R, et al. Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label, randomized, parallel-group study. Epilepsia. 2004 Sep; 45(9):1049-53.

13. Vlasov PN. Use of valproate and carbamazepine in the therapy of epilepsy (guidelines for the practitioner). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10 (4): 129-38. (In Russ.)]. doi: 10.14412/2074-2711-2018-4-129-138

14. Guerrini R, Dravet C, Genton P, et al. Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 1998 May;39(5): 508-12.

15. Crespel A, Genton P, Berramdane M, et al. Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies. Neurology. 2005 Sep 13;65(5):762-4.

16. Karlov VA, Andreeva OV. The use of injection depakin in the treatment of epileptic status. Russkii meditsinskii zhurnal. 2001;20(9):889-93. (In Russ.).

17. Covanis A. Childhood absence epilepsy. In: Panayiotopoulos CP, editor. Atlas of epilepsies. London: Springer-Verlag; 2010. P. 1013-23.

18. Shorvon SD. Oxford Textbook of Epilepsy and Epileptic Seizures. Oxford University Press; 2010.

19. Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000 Oct;9(7):464-8.

20. Cavitt J, Privitera M. Levetiracetam induces a rapid and sustained reduction of generalized spike-wave and clinical absence. Arch Neurol. 2004 Oct;61(10):1604-7.

21. Deckers CL, Hekster YA, Keyser A, et al. Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia. 2001 Nov;42(11):1387-94.

22. Yacubian EM, de Araujo Filho GM. Management issues for patients with idiopathic generalized epilepsies. Epileptology. 2013 Mar; 1(1):1-10.

23. Millul A, Iudice A, Adami M, et al. Alternative monotherapy or add-on therapy in patients with epilepsy whose seizures do not respond to the first monotherapy: an Italian multicenter prospective observational study. Epilepsy Behav. 2013 Sep;28(3):494-500. doi: 10.1016/j.yebeh.2013.05.038. Epub 2013 Jul 26.

24. French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015 Sep 15;85(11):950-7.

25. Gesche J, Khanevski M, Solberg C, et al. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies. Epilepsia. 2017 Apr;58(4):e64-e69. doi: 10.1111/epi.13702. Epub 2017 Feb 23.

26. Karlov VA, Gekht AB, Guzeva VI, et al. Algorithms of mono - and polytherapy in clinical epileptology. Part 1. General principles for selection of pharmacotherapy. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2016;116(6):109-14. (In Russ.)

27. Vlasov PN. Use of valproates in women of childbearing age and pregnant women with epilepsy. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2015;7(1S): 4-9. (In Russ.). doi: 10.14412/2074-2711-2015-1S-4-9

28. Nevitt SJ, Sudell M, Weston J, et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2017 Dec 15;12:CD011412. doi: 10.1002/14651858.CD011412.pub3.

29. Vlasov PN. Use of valproate and carbamazepine in the therapy of epilepsy (guidelines for the practitioner). Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2018;10 (4): 129-38. (In Russ.)]. doi: 10.14412/2074-2711-2018-4-129-138

30. Karlov VA, Andreeva OV. The use of injection depakin in the treatment of epileptic status. Russkii meditsinskii zhurnal. 2001;20(9):889-93. (In Russ.).

31. Shorvon SD. Oxford Textbook of Epilepsy and Epileptic Seizures. Oxford University Press; 2010.

32. Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure. 2000 Oct;9(7):464-8.

33. Deckers CL, Hekster YA, Keyser A, et al. Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia. 2001 Nov;42(11):1387-94.

34. Millul A, Iudice A, Adami M, et al. Alternative monotherapy or add-on therapy in patients with epilepsy whose seizures do not respond to the first monotherapy: an Italian multicenter prospective observational study. Epilepsy Behav. 2013 Sep;28(3):494-500. doi: 10.1016/j.yebeh.2013.05.038. Epub 2013 Jul 26.