Abstract
Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache. In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500 mg and the control group received valproate sodium 400 mg two tablets each day (every 12 h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide–valproate) and 32 patients were in group 2 (valproate–magnesium oxide). The mean number of migraine attacks and days per month was 1.72 ± 1.18 and 2.09 ± 1.70, with a mean duration of 15.50 ± 21.80 h in magnesium group and 1.27 ± 1.27 and 2.22 ± 1.96, with a mean duration 13.38 ± 14.10 in valproate group. This study has shown that 500 mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.
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References
Martin VT, Behbehani MM (2001) Towards a rational understanding of migraine trigger factors. Med Clin N Am 85:911–941
Lipton RB, Liberman JN, Kolodner KB, igal ME, Dowson A, Stewart WF (2003) Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia 23:441–450
Stewart WF, Shechter A, Rasmussen BK (1994) Migraine prevalence. A review of population-based studies. Neurology 44 (6 Suppl 4):S17–S23
Shahbeigi S, Fereshtehnejad SM, Mohammadi N et al (2013) Epidemiology of headaches in Tehran urban area: a population based cross-sectional study in district 8, year 2010. Neurol Sci 34:1157–1166
Shaygannejad V, Janghorbani M, Ghorbani A, Ashtary F, Zakizade N, Nasr V. Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study. Headache 2006;46:642–648
Karimi N, Tavakoli M, Yazdani Charati J, Shamsizade M (2017) Single-dose intravenous sodium valproate (Depakine) versus dexamethasone for the treatment of acute migraine headache: a doubleblind randomized clinical trial. Clin Exp Emerg Med 4 (2):1–8
Rybicka M, Baranowska-Bosiacka I, Żyluk B, Nowacki P, Chlubek D (2012) The role of magnesium in migraine pathogenesis. Potential use of magnesium compounds in prevention and treatment of migraine headaches. J Elementol 17:345–356
Welch KM, Ramadan NM (1995) Mitochondria, magnesium and migraine. J Nneurol Sci 134:9–14
Schoenen J, Sianard -Gainko J, Lenaerts M (1991) Blood magnesium levels in migraine. Cephalalgia 11:97–99
Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G (1991) Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 31:298–301 24
Baudouin-Legros M, Dard B, Guichency P (1986) Hyperreactivity of platelets from spontaneously hypertensive rats. Role of external magnesium. Hypertension 8:694–699
Altura BT, Altura BM (1989) Withdrawal of magnesium causes vasospasm while elevated magnesium produced relaxation of tone in cerebral arteries. Neurosci Lett 20:323–327
Weglicki WB, Phillips TM (1992) Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. Am J Physiol 263:R734–R737
Choi H, Parmar N (2014) The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. Eur J Emerg Med 21:2–9
Peikert A, Wilimzig C, Köhne-Volland F (1996) Prophylaxis of migraine with oral magnesium: results from a prospective, multicenter, placebo-controlled and double-blind randomized study. Cephalalgia 16:257–263
Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, Taner Z, Soycal D, G’bell H, Fischer M (1996) Magnesium in the prophylaxis of migraine—a double-blind, placebo-controlled study. Cephalalgia 16:436–440
Koseoglu E, Talashoglu A, Gonul AS, Kula M (2008) The effects of magnesium prophylaxis in migraine without aura. Magnes Res 21:101–108
Maizels M, Blumenfeld A, Burchette R (2004) A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a randomized trial. Headache 44:885–890
Zhou Y, Gao L (1998) Flunarizine combined with magnesium polarization liquid on treating refractory migraine. Clin Focus 13:664
Hu CS, Zhou LB (2011) Observation of clinical effects of magnesium valproate combined with venlafaxine HCl in 54 individuals with migraine. China Mod Med 18:62
Bian X, Zhu Y, Xia J, Ai HJ, Guo QY, Lu LB, Zhang QW (2013) Clinical observation om potassium magnesium asparate oral soluation combined with flinarizine capsule for migraine prophylaxis. J Comm Med 11:6–7
Tang XY, Lin WZ, Zheng XM, Liu CS (1998) Observation of effects of nimodipine and magnesium sulfate combination for treating migraine. J Qiqihar Med Coll 19:5–6
Alghadeer SM (2016) The efficacy of different oral magnesium supplements for migraine prevention: a literature review. Indones J Pharm 27 (3):174–182
Chiu HY, Yeh TH, Huang YC, Chen PY (2016) Effects of intravenous and oral magnesium on reducing migraine: a meta-analysis of randomized controlled trials. Pain Physician 19:E97–E112
Pringsheim T, Davenport W, Mackie G et al (2012) Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci 39:S1–S59
Teigen L, Boes ChJ (2015) An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine. Cephalalgia 35 (10):912–922
Hering R, Kuritzky A (1992) Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 12:81–84
International Headache Society Committee on Clinical Trials in Migraine (2012) Guidelines for controlled trials of drugs in migraine. Third edition. A guide for investigators. Cephalalgia 32 (1):6–38
Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edn (beta version). Cephalalgia 2013; 33:629–808
Bayliss MS, Dewey JE, Dunlap I, Batenhorst AS, Cady R, Diamond ML, Sheftell F (2003 Dec) A study of the feasibility of Internet administration of a computerized health survey: the headache impact test (HIT). Qual Life Res 12 (8):953–961
Stewart WF, Lipton RB, Kolodner K (2003) Migraine disability assessment (MIDAS) score: relation to headache frequency, pain intensity, and headache symptoms. Headache 43 (3):258–265
Ghorbani A, Chitsaz A (2011) Comparison of validity and reliability of the migraine disability assessment (MIDAS) versus headache impact test (HIT) in an Iranian population. Iran J Neurol 10:39–42
Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ (2003) Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 43 (6):601–610
Tarighat Esfanjani A, Mahdavi R, Ebrahimi Mameghani M, Talebi M, Nikniaz Z, Safaiyan A (2012) The effects of magnesium, l-carnitine, and concurrent magnesium-l-carnitine supplementation in migraine prophylaxis. Biol Trace Elem Res 150 (1–3):42–48
Gaul C, Diener H-C, Danesch U (2015) Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J Headache Pain 16 (1):32
Demirkaya S, Dora B, Topcuoglu MA, Vural O, U HU (2001) A comparative study of magnesium, flunarizine and amitriptyline in the prophylaxis of migraine. J Headache Pain 1 (2000):179–186
Mauskop A, Altura BT, Altura BM (2002) Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual migraine. Headache 42:242–248
Abraham GE, Lubran MM (1981) Serum and red cell magnesium levels in patients with premenstrual tension. Am J Clin Nutr 34 (11):2364–2366
Acknowledgements
The authors wish to thank all the patients who participated in this study and Alimohammady pharmacy due to providing drugs and the Research Vice-Chancellor of Maznadaran University of Medical Sciences for their financial supports and also Clinical Research Development Unit of Bou Ali Sina Hospital to approve this proposal.
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Karimi, N., Razian, A. & Heidari, M. The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study. Acta Neurol Belg 121, 167–173 (2021). https://doi.org/10.1007/s13760-019-01101-x
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DOI: https://doi.org/10.1007/s13760-019-01101-x