The effect of gender differences on the use of valproic acid for migraine prophylaxis

Year 2021, Volume: 4 Issue: 4, 408 - 411, 15.07.2021

Nermin Tepe

https://doi.org/10.32322/jhsm.903329

Abstract

Aim: The efficacy of the drugs used for migraine prophylaxis remains unclear. At our headache polyclinic, when we observed the difference in prophylactic response especially in valproic acid (VA) treatment between genders, the response of male was found to be better than that of females so we wanted to document this difference by collecting data retrospectively
Material and Method: 46 chronic migraine without aura patients with VA who were enrolled in our headache outpatient clinic between 2015 - 2018 were included in the study (29 male, 17 female). In these patients, after VA the frequency of montly attacks between sexes, changes in VAS (Visual analogue scale) scores, single VA prophylaxis and the addition of a second prophylaxis drug were evaluated.
Results: None of the men needed an additional second drug while 11 of 17 women needed the addition of a second drug. There was no gender difference in monthly attack frequency before treatment, whereas monthly attack frequency after treatment with VA was found to be significantly lower in men ( before treatment; female 20,9±11,3 male 17,7±11,5, p>0.05) (after treatment; male 1,2±5,5 female 12,0±12,2, p<0,05). There was no difference between sexes in the pre-treatment VAS scores, but the VAS score was significantly lower in men after treatment with VA (before treatment; female 7,8±0,8 male 8,1±1,2, p>0.05)(after treatment; female 4,4±2,8 male 2,3±2,8, p<0,05). 75,9% of men had no post-treatment migraine attacks, while this rate was 5,9% in women (p<0,05). The dose range of VA treatment wasn't found to be different between genders.
Conclusion: Better response of men with migraine to valproic acid treatment is important in clinical practice, and the reason for this situation may be clarified with further studies

Keywords

Migraine, Valproic Acid, Visual analogue scale

Supporting Institution

-

Project Number

-

Thanks

For critical review support thanks to Dr. Gülseren Büyükşerbetçi

References

• Bolay H, Moskowitz MA. The neurobiology of migraine and transformation of headache therapy. In ‘Neuroscience, Molecular Medicine and the Therapeutic Transformation of Neurology’ 2004; 107- 23.
• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders (ICHD), 3rd edition. Cephalalgia 2018; 38:1-211.
• Parikh SK, Silberstein SD. Preventive Treatment for Episodic Migraine. Neurol Clin 2019; 37: 753-70.
• Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. For the Depakote ER Migraine Study Group. Neurology 2003; 58: 1652-9.
• Klapper JA. Divalproex sodium in migraine prophylaxis: a dose-controlled study.  Cephalalgia 1997;17: 103-8.
• Linde M, Mulleners WM, Chronicle EP, McCrory DC. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013; CD010611.
• Tatyana S, Jae-Young C, Rema R, et alreventive pharmacologic treatments for episodic migraine in adults. J Gen Intern Med 2013; 28: 1225-37.
• Bertilson L. Pharmacogenomics: drugs and the pharmaceutical science, in Historical Aspects of Pharmacogenetics 2001; 1–9.
• Saygi S, Alehan F, Atac FB, Erol I, Verdi H, Erdem R. Multidrug resistance 1 (MDR1) 3435C/T genotyping in childhood drug-resistant epilepsy. Brain Dev 2014; 36: 137-42.
• Ozgon GO, Bebek N, Gul G, Cine N. Association of MDR1 (C3435T) polymorphism and resistance to carbamazepine in epileptic patients from Turkey. Eur Neurol 2008; 59: 67–70.
• Li M, Tan J, Yang X, et al. The ABCB1-C3435T polymorphism likely acts as a risk factor for resistance to antiepileptic drugs. Epilepsy Res 2014; 108: 1052–67.
• Atasayar G, Eryilmaz IE, Karli N, et al. Association of MDR1, CYP2D6, and CYP2C19 gene polymorphisms with prophylactic migraine treatment response. J Neurol Sci 2016; 366:149-54.
• Christensen AF, Esserlind AL, Werge T, Hreinn S, Stefa´nsson K, Olesen J. The influence of genetic constitution on migraine drug responses. Cephalalgia 2016; 36: 624–39.
• Tfelt-Hansen P, Nybye A, Pavbro A, Tfelt-Hansen J. Pharmacokinetic variability of drugs used for prophylactic treatment of migraine. CNS Drug 2017; 31: 389- 403.
• Smith RL, Haslemo T, Refsum H, Molden E. Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid—a large-scale study based on naturalistic therapeutic drug monitoring data. Eur J Clin Pharmacol 2016; 72: 1099–104.
• Perucca E, Grimaldi R, Gatti G, Pirracchio S, Crema F, Frigo GM. Pharmacokinetics of valproic acid in the elderly. Br J Clin Pharmacol 1984; 17: 665–69.
• Ibarra M, Vazquez M, Fagiolino P, Derendorf H. Sex-related differences on valproic acid pharmacokinetics after oral single dose. J Pharmacokinet Pharmacodyn 2013; 40: 479–86.