Serum Lipids and Thyroid Functions in Young Epileptic Patients Undergoing Monotherapy with Valproate or Levetiracetam

Öz

The negative side effects of classic antiepileptics, such as Valproate (VPA), often cause patients to discontinue their use. While the negative effects of VPA on lipid profile and thyroid functions have been well published, data regarding the side effects of new antiepileptics, such as levetiracetam (LEV), are not as conclusive. In this study, we investigated the effects of a well-known antiepileptic, VPA, and a new antiepileptic, LEV, on serum lipid levels and thyroid functions in young epileptic patients. Our study included 79 epileptic patients aged between 18-40 years who were undergoing VPA (n=42) or LEV (n=37) monotherapy for at least two years and 58 healthy subjects. Patients with hypertension, diabetes mellitus, thyroid dysfunction, smoking or alcohol addiction, and those who were being treated with any other drugs were excluded from the study. Fasting total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels were measured for each patient and thyroid function tests were performed. The three groups were compared in terms of these aforementioned parameters. There were no statistical differences in the total cholesterol, LDL-cholesterol, HDL-cholesterol and free-T3 levels between the three groups. The triglyceride levels of the VPA group were significantly higher than those of the LEV and control groups (p=0.0001). While the free-T4 levels of the VPA group were significantly lower than those of the LEV and control groups (p=0.020), TSH levels were higher. The free-T4 and TSH levels did not differ significantly between the LEV and control groups. This study revealed that while the long term use of VPA negatively affected serum triglyceride levels and thyroid functions, LEV did not have any negative effects on these parameters.

Anahtar Kelimeler

• Antiepileptic treatment, valproate, levetiracetam, triglycerides, thyroid function tests

Serum Lipids and Thyroid Functions in Young Epileptic Patients Undergoing Monotherapy with Valproate or Levetiracetam

Öz

Valproat (VPA) gibi klasik antiepileptikler, kimi zaman ilaç değiştirmeyi gerektirecek yan etki profiline sahiplerdir. VPA' nın lipit profili ve tiroit fonksiyonları üzerine olumsuz etkileri iyi araştırılmıştır, levetirasetam (LEV) gibi yeni antiepileptiklerin etkileri ile ilgili çelişkili yayınlar vardır. Bu çalışmada VPA gibi iyi bilinen bir antiepileptikle yeni kuşak antiepileptiklerden LEV' in serum lipit profili ve tiroit fonksiyon testleri üzerine olan etkilerini genç hastalar üzerinde araştırdık. En az iki yıldır VPA (n=42) veya LEV (n=37) monoterapisi alan, 18-40 yaşlar arasında 79 epileptik hasta ve 58 sağlıklı birey çalışmaya alındı. Hipertansiyon, diyabet, tiroit fonksiyon bozukluğu olanlar, başka bir ilaç alan, sigara, alkol kullananlar çalışmaya dahil edilmediler. Hastaların açlık totalkolesterol, LDL-kolesterol, HDL-kolesterol, trigliserit düzeyleri ve tiroit fonksiyon testleri ölçüldü. Gruplar tanımlanan parametreler açısından karşılaştırıldılar. VPA, LEV ve kontrol grupları arasında total-kolesterol, LDL-kolesterol, HDL-kolesterol, serbestT3 değerleri açısından anlamlı bir fark olmamasına rağmen, trigliserit, tiroit-stimulan hormon (TSH) ve serbest-T4 değerleri açısından anlamlı fark vardı. VPA grubunun trigliserit düzeyleri LEV grubundan ve kontrol grubundan (p=0.0001) anlamlı şekilde yüksekti, LEV grubu ile kontrol grubu arasında anlamlı fark yoktu. VPA grubunun serbest-T4 değerleri LEV grubundan ve kontrol grubundan (p=0.020) anlamlı şekilde düşük, TSH değerleri ise anlamlı şekilde yüksekti. LEV ve kontrol grubu arasında serbestT4 ve TSH açısından anlamlı fark saptanmadı. Bu çalışmada uzun dönem kullanımda VPA' nın serum trigliserit düzeyleri tiroit fonksiyonları açısından olumsuz etkisi gözlenmiş, LEV' in ise bu parametrelere olumsuz etkisinin olmadığı sonucuna ulaşılmıştır

Anahtar Kelimeler

• Antiepileptik tedavi, valproat, levetirasetam, trigliserit, tiroit fonksiyon testleri

Kaynakça

1. Chuang YC, Chuang HY, Lin TK, et al. Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. Epilepsia 2012;53(1):120-8.
2. Yilmaz E, Doşan Y, Gürgöze MK, Güngör S. Serum lipid changes during anticonvulsive treatment serum lipids in epileptic children. Acta Neurol Belg 2001;101(4):217-20
3. Lopinto-Khoury C, Mintzer S. Antiepileptic drugs and markers of vascular risk. Curr Treat Options Neurol 2010;12(4):300-8.
4. Hamed SA, Hamed EA, Hamdy R, Nabeshima T. Vascular risk factors and oxidative stress as independent predic- tors of asymptomatic atherosclerosis in adult patients with epilepsy Epilepsy Res 2007;74(2-3): 183-92
5. Pylvänen V, Pakarinen A, Knip M, Isojärvi J. Insulin-related metabolic changes during treatment with valproate in pa- tients with epilepsy Epilepsy Behav 2006;8(3):643-8.
6. Mintzer S, Skidmore CT, Abidin CJ, et al. Effects of anti- epileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol 2009;65(4):448-56.
7. Belcastro V, D'Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013;107(1-2)
8. Kullo IJ, Ballantyne CM. Conditional risk factors for ath- erosclerosis. Mayo Clin Proc 2005;80(2):219-30.

9. Carmena R, Duriez P, Fruchart JC. Atherogenic lipopro- tein particles in atherosclerosis. Circulation 2004;109(23 Suppl 1):III2-7
10. Mohanraj R, Norrie J, Stephen LJ, Kelly K, Hitiris N, Brodie MJ. Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study. Lancet Neurol 2006;5(6):481-7
11. Cockerell OC, Johnson AL, Sander JW, Hart YM, Goodridge DM, Shorvon SD. Mortality from epilepsy: re- sults from a prospective population-based study. Lancet 1994;344(8927):918-21
12. Kim DW, Lee SY, Shon YM, Kim JH. Effects of new anti- epileptic drugs on circulatory markers for vascular risk in patients with newly diagnosed epilepsy. Epilepsia 2013;54(10):e146-9.
13. Ozdemir O, Yakut A, Dinleyici EC, Aydogdu SD, Yarar C, Colak O. Serum asymmetric dimethylarginine (ADMA), homocysteine, vitamin B(12), folate levels, and lipid pro- files in epileptic children treated with valproic acid. Eur J Pediatr 2011;170(7):873-7
14. Meltzer HY, Bonaccorso S, Bobo WV, Chen Y, Jayathilake K. A 12-month randomized, open-label study of the meta- bolic effects of olanzapine and risperidone in psychotic patients: influence of valproic acid augmentation. J Clin Psychiatry 2011;72(12):1602-10.
15. Pylvänen V, Knip M, Pakarinen A, Kotila M, Turkka J, Isojärvi JI. Serum insulin and leptin levels in valproate- associated obesity. Epilepsia 2002;43(5):514-7.
16. Voudris KA, Attilakos A, Katsarou E, et al. Early and per- sistent increase in serum lipoprotein (a) concentrations in epileptic children treated with carbamazepine and sodium valproate monotherapy. Epilepsy Res 2006;70(2- 3):211-7
17. Sonmez FM, Demir E, Orem A, et al. Effect of antiepi- leptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.
18. Isojärvi JI, Taubİll E, Pakarinen AJ, et al. Altered ovar- ian function and cardiovascular risk factors in valproate- treated women. Am J Med 2001;111(4):290-6.
19. Sozuer DT, Atakil D, Dogu O, Baybas S, Arpaci B. Serum lipids in epileptic children treated with carbamazepine and valproate. Eur J Pediatr 1997;156(7):565-7.
20. Erdemir A, Cullu N, Yiş U, Demircioğlu F, Kir M, Cakmakçi H, Unal N, Dirik E. Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treat- ed with valproic acid. Brain Dev 2009;31(10):713-6
21. Verrotti A, D'Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev 2011;12(5):e32-43
22. Elmslie JL, Porter RJ, Joyce PR, Hunt PJ, Shand BI, Scott RS. Comparison of insulin resistance, metabolic syndrome and adiponectin in overweight bipolar patients taking sodium valproate and controls. Aust N Z J Psychiatry 2009;43(1):53-60
23. Verrotti A, Manco R, Agostinelli S, Coppola G, Chiarelli F. The metabolic syndrome in overweight epileptic patients treated with valproic acid Epilepsia 2010;51(2):268-73.
24. Celik C, Abali R, Tasdemir N, Guzel S, Yuksel A, Aksu E, Yılmaz M. Is subclinical hypothyroidism contributing dys- lipidemia and insulin resistance in women with polycystic ovary syndrome? Gynecol Endocrinol 2012;28(8):615-8
25. Hernández-Mijares A, Jover A, Bellod L, Bañuls C, Solá E, Veses S, Víctor VM, Rocha M. Relation between lipo- protein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism. Clin Endocrinol (Oxf) 2013;78(5):777-82
26. Pearce EN. Hypothyroidism and dyslipidemia: modern con- cepts and approaches. Curr Cardiol Rep. 2004;6(6):451-6.
27. Lai EC, Yang YH, Lin SJ, Hsieh CY. Use of antiepileptic drugs and risk of hypothyroidism. Pharmacoepidemiol Drug Saf 2013;22(10):1071-9
28. Yılmaz U, Yılmaz TS, Akıncı G, Korkmaz HA, Tekgül H. The effect of antiepileptic drugs on thyroid function in children. Seizure 2014;23(1):29-35
29. Kim SH, Chung HR, Kim SH, Kim H, Lim BC, Chae JH, Kim KJ, Hwang YS, Hwang H. Subclinical hypothyroidism dur- ing valproic acid therapy in children and adolescents with epilepsy. Neuropediatrics 2012;43(3):135-9.