Use of valproate and carbamazepine in the therapy of epilepsy (guidelines for the practitioner)

The paper gives comparative data on the efficacy and tolerability of valproic acid (VA, valproate) and carbamazepine (CBZ) for different types of epilepsy and seizures in different age and clinical groups. The results of studies suggest that despite a more than 50-year history of their effective use, the extended-release formulations of VA and CBZ remain the drugs of first choice for many types of epilepsy.

CBZ is effective for focal epilepsy and isolated generalized tonic-clonic seizures. However, its use is substantially limited by properties, such as cytochrome P450 induction and autoinduction, high drug-drug interactions, the aggravation of absences, negative myoclonus, myoclonic and atonic seizures, an effect on the profile of steroid sex hormones, elevated concentrations of atherogenic lipids and cholesterol, myocardial conduction disorders, and hyponatremia.

Due to the multiple mechanism of action, VA is prescribed for almost all types of epilepsy and seizures in patients of different ages. VA should not be used (if the clinical situation allows) in women of childbearing age, in some infantile epileptic encephalopathy, inherited metabolic diseases, and chromosomal abnormalities. Effectiveness against different types of seizures and epilepsy, good tolerability, minimal aggravation risk, high retention rate of monotherapy, the presence of a variety of dosage forms, and favorable pharmacokinetic and pharmacodynamic profiles still make VA essential in many clinical situations.

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59. Meador KJ, MD, Baker GA, et al. Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs. N Engl J Med. 2009 Apr 16;360(16):1597-605. doi: 10.1056/NEJMoa0803531.

60. Dmitrenko DV, Shnaider NA, Strotskaya IG, et al. Mechanisms of valproate-induced teratogenesis. Nevrologiya, neiropsikhi-atriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1S):89—96. (In Russ.). doi: 10.14412/2074-2711-2017-1S-89-96

61. Karlov VA, Zhidkova IA, Serkina AV, Kozho-karu AB. Intellectual, psychomotor and speech development of children born by epileptic mothers. Zhurnal nevrologii ipsikhiatrii im. S.S. Korsakova. Epilepsiya. 2010;(3):25-30. (In Russ.).

62. Vlasov PN, Petrukhin VA, Karlov VA, et al. Antiepileptic Drug Therapy During Pregnancy In Moscow Region: Comparing of 1998 and 2013 years. Epilepsia. 2014;55(Suppl. 2):130. doi: 10.1111/epi.12675

63. Anisimova DV, Magzhanov RV, Vlasov PN, et al. Analysis of hormone-dependent pathology in female patients with juvenile myoclonic epilepsy. Nevrologiya, neiropsikhia-triya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1S):32-8. (In Russ.). doi: 10.14412/2074-2711-2017-1S-32-38

64. Goldberg-Stern H, Yaacobi E, Phillip M, de Vries L. Endocrine effects of valproic acid therapy in girls with epilepsy: A prospective study. Eur JPaediatr Neurol. 2014 Nov;18(6): 759-65. doi: 10.1016/j.ejpn.2014.07.004. Epub 2014 Jul 29.

65. Lind LK, Komen J, Wettermark B, et al. Valproic acid utilization among girls and women in Stockholm: Impact of regulatory restrictions. Epilepsia Open. 2018 Jun 13;3(3):357-363. doi: 10.1002/epi4.12228.eCollection2018 Sep.

66. Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Lancet Neurol. 2012 Sep;11(9): 803-13. doi: 10.1016/S1474-4422(12)70103-5. Epub 2012 Jul 16.

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68. Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: An expert consensus statement from the Task Force on Therapeutic Strategies of the ILAE Commission on Neuropsychobiology. Epilepsia. 2013 Jan;54(1):199-203. doi: 10.1111/j.1528-1167.2012.03688.x. Epub 2012 Sep 20.

69. Bruun E, Virta LJ, Ka lvia inen R, Kera nen T. Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy. Epilepsy Behav. 2017 Aug; 73:71-76. doi: 10.1016/j.yebeh.2017.05.022. Epub 2017 Jun 14.

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71. Makinen J, Rainesalo S, Raitanen J, et al. Discontinuation of carbamazepine due to concerns of longterm consequences of enzyme induction. Epilepsia Open. 2018 Jun 8;3(3): 340-347. doi: 10.1002/epi4.12227.eCollection2018 Sep.

72. Bano S, Zuberi NA, Alam SM. Correlation between Hyperhomocysteinemia and Common Carotid Artery Intima media Thickness in Carbamazepine treated Epileptic patients using Ultrasonography. Pak J Med Sci. 2017 Sep-Oct; 33(5):1205-1209. doi:10.12669/pjms.335.12982.

73. Bardai A, Blom MT, Van Noord C, et al. Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications. Heart. 2015 Jan;101(1):17-22. doi: 10.1136/heartjnl-2014-305664. Epub 2014 Jul 16.

74. Ruiz-Gimernez J, Sanchez-Alvarez JC, Canadillas-Hidalgo F, Serrano-Castro PJ. Antiepileptic treatment in patients with epilepsy and other comorbidities. Seizure. 2010 Sep;19(7): 375-82. doi: 10.1016/j.seizure.2010.05.008. Epub 2010 Jun 15.

75. Hollingworth SA, Eadie MJ. Antiepileptic drugs in Australia: 2002-2007. PharmacoepidemiolDrug Saf. 2010 Jan;19(1): 82-9. doi: 10.1002/pds.1871.