The application of valproic acid in epilepsy and comorbidities as a broad-spectrum anti-seizure medication_Journal of Epilepsy

Authors：

ZHANG Enhui , ZHANG Hesheng , CHEN Yujie , OU Zhujing , ZHOU Dong ,  WU Xintong

Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

WU Xintong, Email: 36853839@qq.com

Keywords：

Valproic acid; Epilepsy; Comorbidities; Combination therapy; Adverse reactions

DOI：

10.7507/2096-0247.202306009

Video：

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Valproic acid can reduce the frequency of seizures through various mechanisms and is widely used in clinical practice as a monotherapy or adjunctive treatment for various types of epilepsy and epileptic syndromes. In addition, valproic acid has significant therapeutic effects on comorbidities associated with epilepsy, such as migraines and psychiatric disorders. It can also be effective in terminating status epilepticus and is commonly used as a broad-spectrum antieseizure medication in clinical settings. However, valproic acid has side effects such as teratogenicity, infertility, and menstrual disorders. Additionally, when used in combination with other drugs, the interactions between medications should be carefully considered. Therefore, in clinical practice, it is necessary to strictly adhere to the indications and dosage regimens for the use of valproic acid. This article provides a comprehensive review of the use of valproic acid in different types of seizures, epileptic syndromes, comorbidities associated with epilepsy, post-craniotomy cases, status epilepticus, and special populations. It also summarizes the combination therapy of valproic acid with other drugs, providing a basis for the rational use of valproic acid and individualized drug treatment selection for epilepsy patients.

Citation： ZHANG Enhui, ZHANG Hesheng, CHEN Yujie, OU Zhujing, ZHOU Dong, WU Xintong. The application of valproic acid in epilepsy and comorbidities as a broad-spectrum anti-seizure medication. Journal of Epilepsy, 2023, 9(5): 393-399. doi: 10.7507/2096-0247.202306009 Copy

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22.	Wu M, Hao N, Yan B, et al. Status epilepticus in pregnant women with epilepsy after valproate adjustment: A case series. Seizure, 2016, 43: 39-41.
23.	Tomson T, Marson A, Boon P, et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia, 2015, 56(7): 1006-1019.
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27.	Chen WB, Gao R, Su YY, et al. Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study. Eur J Neurol, 2011, 18(12): 1391-1396.
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30.	Al-Quteimat O, Laila A. Valproate Interaction With Carbapenems: Review and Recommendations. Hosp Pharm, 2020, 55(3): 181-187.
31.	Albanji M, Alshehri S, Eljaaly K. The effect of erythromycin and clarithromycin versus azithromycin on serum valproate concentration. Saudi Pharm J, 2022, 30(4): 337-339.
32.	Zhou C, Sui Y, Zhao W, et al. The critical interaction between valproate sodium and warfarin: case report and review. BMC Pharmacol Toxicol, 2018, 19(1): 60.

1. 中国抗癫痫协会. 临床诊疗指南: 癫痫病分册. 人民卫生出版社, 2023.
2. Beghi E. Addressing the burden of epilepsy: many unmet needs. Pharmacol Res, 2016, 107: 79-84.
3. Ma XP, Li YP, Yang R, et al. Challenges of patients with epilepsy and measures for improving epilepsy care in western China: a qualitative study. Epilepsy Res, 2021, 178: 106788.
4. Wang WZ, Wu JZ, Wang DS, et al. The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study. Neurology, 2003, 60(9): 1544-1545.
5. Peterson GM, Naunton M. Valproate: a simple chemical with so much to offer. J Clin Pharm Ther, 2005, 30(5): 417-421.
6. Tomson T, Battino D, Perucca E. Valproic acid after five decades of use in epilepsy: time to reconsider the indications of a time-honoured drug. Lancet Neurol, 2016, 15(2): 210-218.
7. Singh D, Gupta S, Verma I, et al. Hidden pharmacological activities of valproic acid: a new insight. Biomed Pharmacother, 2021, 142: 112021.
8. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med, 2000, 342(5): 314-319.
9. Nickels K, Kossoff EH, Eschbach K, et al. Epilepsy with myoclonic-atonic seizures (Doose syndrome): clarification of diagnosis and treatment options through a large retrospective multicenter cohort. Epilepsia, 2021, 62(1): 120-127.
10. Kanner AM, Bicchi MM. Antiseizure medications for adults with epilepsy: a review. JAMA, 2022, 327(13): 1269-1281.
11. Keezer MR, Sisodiya SM, Sander JW. Comorbidities of epilepsy: current concepts and future perspectives. Lancet Neurol, 2016, 15(1): 106-115.
12. Stevenson SB. Epilepsy and migraine headache: is there a connection? J Pediatr Health Care, 2006, 20(3): 167-171.
13. Haut SR, Bigal ME, Lipton RB. Chronic disorders with episodic manifestations: focus on epilepsy and migraine. Lancet Neurol, 2006, 5(2): 148-157.
14. 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.
15. Villanueva V, Artal J, Cabeza-Alvarez CI, et al. Proposed recommendations for the management of depression in adults with epilepsy: an expert consensus. Neurol Ther, 2023, 12(2): 479-503.
16. Munger Clary HM. Anxiety and epilepsy: what neurologists and epileptologists should know. Curr Neurol Neurosci Rep, 2014, 14(5): 445.
17. Kanemura H, Sano F, Tando T, et al. EEG improvements with antiepileptic drug treatment can show a high correlation with behavioral recovery in children with ADHD. Epilepsy Behav, 2013, 27(3): 443-448.
18. Schubert R. Attention deficit disorder and epilepsy. Pediatr Neurol, 2005, 32(1): 1-10.
19. Han SA, Yang EJ, Song MK, et al. Effects of lamotrigine on attention-deficit hyperactivity disorder in pediatric epilepsy patients. Korean J Pediatr, 2017, 60(6): 189-195.
20. Gul A, Mehreen S. Effectiveness of Lacosamide on everyday cognitive deficits, psychiatric symptoms and resilience in patients with epilepsy. J Pak Med Assoc, 2020, 70(9): 1611-1615.
21. Liang S, Fan X, Chen F, et al. Chinese guideline on the application of anti-seizure medications in the perioperative period of supratentorial craniocerebral surgery. Ther Adv Neurol Disord, 2022, 15: 17562864221114357.
22. Wu M, Hao N, Yan B, et al. Status epilepticus in pregnant women with epilepsy after valproate adjustment: A case series. Seizure, 2016, 43: 39-41.
23. Tomson T, Marson A, Boon P, et al. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia, 2015, 56(7): 1006-1019.
24. 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, 101(1): 17-22.
25. Yang CY, Dao RL, Lee TJ, et al. Severe cutaneous adverse reactions to antiepileptic drugs in Asians. Neurology, 2011, 77(23): 2025-2033.
26. Shukla S, Rastogi S, Abdi SAH, et al. Severe cutaneous adverse reactions in Asians: Trends observed in culprit anti-seizure medicines using VigiBase(R). Seizure, 2021, 91: 332-338.
27. Chen WB, Gao R, Su YY, et al. Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study. Eur J Neurol, 2011, 18(12): 1391-1396.
28. Lee SA, Lee JK, Heo K. Coma probably induced by lorazepam-valproate interaction. Seizure, 2002, 11(2): 124-125.
29. Morris RG, Black AB, Lam E, et al. Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? Ther Drug Monit, 2000, 22(6): 656-660.
30. Al-Quteimat O, Laila A. Valproate Interaction With Carbapenems: Review and Recommendations. Hosp Pharm, 2020, 55(3): 181-187.
31. Albanji M, Alshehri S, Eljaaly K. The effect of erythromycin and clarithromycin versus azithromycin on serum valproate concentration. Saudi Pharm J, 2022, 30(4): 337-339.
32. Zhou C, Sui Y, Zhao W, et al. The critical interaction between valproate sodium and warfarin: case report and review. BMC Pharmacol Toxicol, 2018, 19(1): 60.

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