Effect of valproic acid coadministred with lamotrigine on epileptic patients' ammonia_Journal of Epilepsy

Authors：

LI Yinchao ¹ , CHEN Shuda ¹ , LIN Wanron ¹ , ZHAO Yiran ¹ , CHEN Aohan ¹ ,  ZHOU Liemin ^1,2

1. Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China;
2. Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510030, China;

Corresponding?author：

ZHOU Liemin, Email: lmzhou56@163.com

Keywords：

Epilepsy; Valproic acid; Lamotrigine; Blood ammonia

DOI：

10.7507/2096-0247.20200065

Video：

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Objective To investigate the effect of valproic acid (VPA) coadministred with lamotrigine (LTG) on epileptic patients' ammonia and evaluate the influencing factors of elevated blood ammonia in epileptic patients.Methods A retrospective analysis of clinical data from 146 patients with epilepsy (including newly diagnosed epilepsy patients) who were admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University from May 2018 to April 2020 was performed. The patients were divided into no antiepileptic drug group (group A), VPA group only (group B) and VPA combined LTG group (group C), and the concentration of the blood ammonia of the patients were analyzed.Result The average ammonia levels in groups A, B and C were (18.14±1.19), (25.89±0.87) and (36.60±4.34) μmol/L, and the incidence of blood ammonia higher than normal were 2.77%, 8.89% and 20.0%, respectively.The difference between group B and group A and group C were statistically significant (P<0.05), the difference between group C and group A was statistically significant (P<0.05).Conclusion Patients with epilepsy who use VPA were at increased risk of blood ammonia and LTG can increase ammonia in epileptic patients who were treated with VPA. So when VPA was combined with LTG, more attention should be paid to ammonia of patient to avoid adverse reactions.

Citation： LI Yinchao, CHEN Shuda, LIN Wanron, ZHAO Yiran, CHEN Aohan, ZHOU Liemin. Effect of valproic acid coadministred with lamotrigine on epileptic patients' ammonia. Journal of Epilepsy, 2020, 6(5): 407-409. doi: 10.7507/2096-0247.20200065 Copy

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7.	Aires CC, van Cruchten A, Ijlst L, <italic>et al</italic>. New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA. J Hepatol, 2011, 55(2): 426-434.
8.	Nakajima Y, Ito T, Maeda Y, <italic>et al</italic>. Evaluation of valproate effects on acylcarnitine in epileptic children by LC-MS/MS. Brain Dev, 2011, 33(10): 816-823.
9.	Chicharro AV, de Marinis AJ, Kanner AM. The measurement of ammonia blood levels in patients taking valproic acid: looking for problems where they do not exist? Epilepsy & behavior, 2007, 11(3): 361-366.
10.	Yamamoto Y, Takahashi Y, Suzuki E, <italic>et al</italic>. Risk factors for hyperammonemia associated with valproic acid therapy in adult epilepsy patients. Epilepsy Res, 2012, 101(3): 202-209.
11.	Fan CC, Huang MC, Liu HC. Lamotrigine might potentiate valproic acid-induced hyperammonemic encephalopathy. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(7): 1747-1748.
12.	林劍明. 丙戊酸誘發癲癇患兒高氨血癥的相關因素分析. 中國婦幼健康研究, 2018, 29(6): 741-743.

1. Lichter-Konecki U. Profiling of astrocyte properties in the hyperammonaemic brain: shedding new light on the pathophysiology of the brain damage in hyperammonaemia. J Inherit Metab Dis, 2008, 31(4): 492-502.
2. Lewis C, Deshpande A, Tesar GE, <italic>et al</italic>. Valproate-induced hyperammonemic encephalopathy: a brief review. Curr Med Res Opin, 2012, 28(6): 1039-1042.
3. Murphy JV, Marquardt K. Asymptomatic hyperammonemia in patients receiving valproic acid. Arch Neurol, 1982, 39(9): 591-592.
4. Kim JM, Ryu WS, Hwang YH, <italic>et al</italic>. Aggravation of ataxia due to acetazolamide induced hyperammonaemia in episodic ataxia. J Neurol Neurosurg Psychiatry, 2007, 78(7): 771-772.
5. Adams EN, Marks A, Lizer MH. Carbamazepine-induced hyperammonemia. Am J Health Syst Pharm, 2009, 66(16): 1468-1470.
6. Labib PL, Wing S, Bhowmik A. Transient hyperammonaemia in a patient with confusion: challenges with the differential diagnosis. BMJ Case Rep, 2011, 9: pii: bcr0320113961.
7. Aires CC, van Cruchten A, Ijlst L, <italic>et al</italic>. New insights on the mechanisms of valproate-induced hyperammonemia: inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA. J Hepatol, 2011, 55(2): 426-434.
8. Nakajima Y, Ito T, Maeda Y, <italic>et al</italic>. Evaluation of valproate effects on acylcarnitine in epileptic children by LC-MS/MS. Brain Dev, 2011, 33(10): 816-823.
9. Chicharro AV, de Marinis AJ, Kanner AM. The measurement of ammonia blood levels in patients taking valproic acid: looking for problems where they do not exist? Epilepsy & behavior, 2007, 11(3): 361-366.
10. Yamamoto Y, Takahashi Y, Suzuki E, <italic>et al</italic>. Risk factors for hyperammonemia associated with valproic acid therapy in adult epilepsy patients. Epilepsy Res, 2012, 101(3): 202-209.
11. Fan CC, Huang MC, Liu HC. Lamotrigine might potentiate valproic acid-induced hyperammonemic encephalopathy. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(7): 1747-1748.
12. 林劍明. 丙戊酸誘發癲癇患兒高氨血癥的相關因素分析. 中國婦幼健康研究, 2018, 29(6): 741-743.

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