Eslami, Mohammad Hassan

Rahimdel, Abolghasem

Zeinali, Ahmad

English

eCommons@AKU

Pakistan Journal ofNeurological Sciences (PJNS)Volume 2 | Issue 2 Article 37-2007A Randomized Controlled Study OfmagnesiumSulfate Versusdihydroergotamine in TheManagement Ofacute Migraine AttacksAbolghasem RahimdelShahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranMohammad Hassan EslamiShahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranAhmad ZeinaliShahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranFollow this and additional works at: https://ecommons.aku.edu/pjnsPart of the Neurology CommonsRecommended CitationRahimdel, Abolghasem; Eslami, Mohammad Hassan; and Zeinali, Ahmad (2007) "A Randomized Controlled Study OfmagnesiumSulfate Versusdihydroergotamine in The Management Ofacute Migraine Attacks," Pakistan Journal of Neurological Sciences (PJNS): Vol.2 : Iss. 2 , Article 3.Available at: https://ecommons.aku.edu/pjns/vol2/iss2/3Headache attacks are one of  the most commoncomplaints presenting to the emergency room,1 w i t hwomen twice as likely to present with migraine headachesas compared to men.2 Dihydroergotamine (DHE) iscommonly used for pain relief during acute migraine, butthis drug has limiting side effects, such as nausea andvomiting.3 Research for drugs or components that relievepain during a severe attack without side effects is ongoing.Magnesium deficiency has been postulated to play a rolein migraine pathophysiology,4 and it is  hypothesized thatmagnesium sulfate can provide relief from headachescaused by migraine. In this study, the therapeutic effectsof magnesium sulfate in acute migraine were comparedwith the beneficial effects of DHE.METHODSThe study was conducted in the emergency department ofShahid Sadoughi Hospital (Yazd, Iran) between March andNovember 2006. A sample of 120 patients (60 in eachgroup) presenting with headache due to migraine wereincluded. The study protocol was reviewed and approvedby the University's Ethics Committee and informed consentwas obtained from all patients. Age of less than 15 years,allergic reaction to magnesium sulfate, abnormal findingsin physical examination, blood calcium level less than 8.3mg/dl, and presence of cardiac or renal problems were theexclusion criteria for the study. Patients randomly receivedeither 1g magnesium sulfate in 100 ml normal salinesolution or DHE (standard treatment of acute migraine).Patients and the treating physician were blinded to thetreatment type used for  each pat ient, wi th theidentification code assigned to each case kept confidentialuntil after the primary analysis. Patients evaluated theirpain on the visual analogue scale (VAS) with endpoints ofnone and greatest pain.0-10 The patients were requestedto evaluate their pain on the VAS again at 30, 60 and 90minutes after receiving the intervention. Statisticalanalysis employed t-test and chi-square test, with thelevel of significance set at 95%.RESULTSOf 120 patients enrolled in the study, 80 (66.7%) werefemale and 40 (33.3%) male. Classic migraine waspresent in 47 patients (39.2%), while 73 patientsV O L .  2 ( 2 )   A P R  -  J U N  2 0 0 7P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  92O R I G I N A L  A R T I C L EA RANDOMIZED CONTROLLED STUDY OFMAGNESIUM SULFATE VERSUSDIHYDROERGOTAMINE IN THE MANAGEMENT OFACUTE MIGRAINE ATTACKSAbolghasem Rahimdel, Mohammad Hassan Eslami and Ahmad ZeinaliShahid Sadoughi University of Medical Sciences and Health Services, Yazd, IranCorrespondence to: Dr Rahimdel, Neurology Ward, Shahid Sadoughi Hospital, Bou Ali Avenue, Safaieh, P.O. Box 734, Yazd, Iran. Tel: +98 351 454 45, Fax: +98 351 454 46. Email: rahimdel30142@yahoo.com   ABSTRACTIntroduction: There is a hypothesis that magnesium sulphate can provide relief from headaches caused by migraine. In thisstudy, we have compared the effects of magnesium sulfate and dihydroergotamine (DHE) in the management of severemigraine headaches. M e t h o d s : The study includes 120 patients who presented to our hospital's emergency room withheadache due to migraine. They randomly received either 100 ml normal saline solution with 1g of magnesium sulfate ordihydroergotamine mesylate, which is standard acute migraine treatment. Patients evaluated their pain on the visual analoguescale (VAS) at 30, 60 and 90 minutes after the intervention. Results: Thirty minutes after intervention, mean VAS was 6 ±1.29 in the magnesium sulfate group and 5.85 ± 1.02 in the DHE group. Sixty minutes after intervention, it was 4.08 ± 1.67(magnesium sulfate) and 4.62 ± 1.21 (DHE). While at 90 minutes it was 2.48 ± 1.61 (magnesium sulfate) and 3.48 ± 1.26(DHE). Pain score comparisons were statistically significant at 60 and 90 minutes, although not at 30 minutes. The two groupswere similar in terms of gender distribution and migraine subtype. Conclusion: Treatment with 1g of magnesium sulfate in100 ml normal saline solution provides significant pain relief in migraine without any serious side effects.Pak J Neurol Sci 2007; 2(2):92-95V O L .  2 ( 2 )   A P R  -  J U N  2 0 0 7P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  93(60.8%) had common pattern migraine. Mean serummagnesium level before intervention was 1.99 ± 0.81mg/dl, while mean serum calcium level before interventionwas 9.10 ± 0.83 mg/dl.       Tables 1 and 2 summarize the VAS results. At 30 minutesafter intervention, mean VAS was 6 ± 1.29 in themagnesium group and 5.85 ± 1.02 in the DHE group,which changed to 4.08 ± 1.67 (magnesium group) and4.62 ± 1.21 (DHE group) at 60 minutes, and 2.48 ±1.61 (magnesium group) versus 3.48 ± 1.26 (DHEgroup) at 90 minutes (p < 0.01) . A significant reductionin pain intensity at 60 and 90 minutes after treatment,compared with baseline, was seen in both groups (at 60min, p = 0.047; at 90 min, p < 0.01). Mean VAS ofpatients in the magnesium group was significantly lowerthan the ergotamine group. This reduction in pain intensitywas not different between the groups at 30 minutes afterintervention (p = 0.48; figures 1 and 2) Patients were also divided into two groups according totheir baseline magnesium level (above or below 1.5).There were significant differences between mean VASscore at 60 and 90 minutes after intervention among thetwo groups (p = 0.004 for 60 min; p < 0.01 for 90 min).At 30 minutes, however, the scores in both groups weresimilar (Table 3). VAS scores also did not differ accordingto gender (Table 2) or migraine type. DISCUSSIONIncreasing evidence supports a role for both systemic andbrain magnesium deficiency in patients with migraine,especially migraine localized to the occipital lobes.Magnesium normally maintains a strongly coupled state ofmitochondrial oxidative phosphorylation. It also plays arole in gating the N-methyl-D-aspartate (NMDA) subtypeof glutamate receptors. Magnesium deficiency causesFigure 1: Mean and confidence interval of VAS inboth group of study at 60 min after interventionFigure 2: Mean and confidence interval of VAS inboth group of study at 90 min after interventionTable 1: Comparison between mean and standard deviation of VAS at 0.5, 1and 1.5 hours after intervention in both study groupsVASGroup of study 0.5 hours after 1 hour after 1.5 hour afterintervention intervention interventionNumber 60 60 60Mean 6 4.08 2.48S.D 1.29 1.67 1.61Number 60 60 60Mean 5.85 4.62 3.48S.D 1.02 1.21 1.26Number 120 120 120Mean 5.93 4.35 2.98S.D 1.16 1.47 1.52(P-value = 0.48 for 0.5 hour, P-value = 0.047 for 1 hour, P-value = 00.0 for 1.5 hours after trial) MagnesiumSulfateDihydroer-gotamineTotalTable 2: Comparison between mean and standard deviation of VAS at 0.5, 1and 1.5 hours after intervention in both sex groupsVASGroup of study 0.5 hours after 1 hour after 1.5 hour afterintervention intervention interventionNumber 40 40 40Mean 5.97 4.55 3.10S.D 1.33 1.57 1.52Number 80 80 80Mean 5.90 4.25 2.93S.D 1.07 1.43 1.53Number 120 120 120Mean 5.92 4.35 2.98S.D 1.16 1.48 1.52(P-value = 0.74 for 0.5 hour, P-value = 0.29 for 1 hour, P-value = 0.56 for 1.5 hours aftertrial)MaleFemaleTotalMagnesiumMagnesiumErgotamineErgotamineinstability of neuronal polarization because of a loss ofionic homeostasis, leading to neuronal hyperexciitabilityand a lower threshold for spontaneous depolarization.5Migra ine pathophysiology remains incomplete lyunderstood. Evidence suggests that vascular componentsplay a basic role in the pathophysiology of migraine. Ourstudy has shown magnesium administ rat ion as atreatment strategy for migraine. The results of our studyshow that 100 ml normal saline solution with 1 g ofmagnesium sulfate provided significant pain relief inmigraine headache attacks presenting to the ER.  It isimportant to note that these effects were most noticeableat 60 and 90 minutes and were not appreciated at 30minutes after intervention. Mauskop and Altura havereported that around 50% of migraineurs had low levels ofmagnesium during migraine attacks. Magnesium infusioncauses rapid and continuous relief during migraineattacks.4,6Other studies have compared the efficacy of magnesiumsulfate with other drugs or placebo in migraine. Mauskopet al note that magnesium therapy in patients with lowbaseline levels of serum magnesium had decreasing paineffects.6,7 On the other hand, Ginder and co-workers havereported in their study that serum levels of magnesiumsulfate had no relationship with the response of migrainepatients to magnesium infusion.8 Barkley and colleaguesconfirmed the sensitivity of spontaneous neural dischargesto magnesium in migraine patients who had low levels ofintracellular magnesium.9Thompson has outlined that therapeutic effects of drugscome from three components: a direct drug effect,reflecting the natural course of the disease with or withouta placebo effect; the reputation of the treating physicianor the establishment he represents; and the culture andexpectation of patients.1 0 In chronic diseases such asmigraine, prior treatment history may influence patients'expectation of the pain relief properties of drugs. Theroute of administration of a drug can also influence therelief response, possibly as an augmentation of theplacebo effect.Bigal and colleagues have reported that magnesiumsulfate can reduce all symptoms in migraine with orwithout aura.1 1 Other investigators have reported that adisturbance in magnesium ion homeostasis in the brainunderlies the pathogenesis of migraine disease.1 2L iterature repor ts  indicate that 1 g int ravenousmagnesium sulfate is an efficient, safe, and well tolerateddrug for the treatment of migraine attacks. It is possiblethat magnes ium sulfate may be used in a broaderspectrum of patients other than those in the acute attackphase.13Our results are subject to certain limitations. We enrolledall patients presenting with migraine headache regardlessof a prior history of migraine or any co-morbid conditions.We also did not ask about symptoms associated withmigraine (such as photophobia or nausea) and reliedexclusively on pain relief as the sole outcome measure.The study did not conduct follow-up assessments beyond90 minutes, and the long-term beneficial of magnesiumbeyond this durat ion,  i f any, are unknown. Forconfirmation of our results, the effect of magnesiumsulfate in acute migraine should be examined in large-scale studies.REFERENCES1. Schull M. Headache and facial pain. In: Tintinalli JE,Kelen GD, Stapczynski JS, eds. Emergency medicine: a comprehensive study guide. 5th ed. New York: McGraw-Hill, 2000:1422-30.2. Lipton RB, Stewart WF, Scher AI. Epidemiology of migraine. In: Diener HC, editor. Drug treatment of migraine and other headaches. Basel: Karger, 2000:2-15. 3. Tfelt-Hansen P, Saxena PR, Dalöf C, Pascual J, Lainez M, Henry P et al.  Ergotamine in the acute treatment of migraine: a review and European Consensus. Brain 2000; 123: 9-18.4. Alutra BM. Calcium antagonist properties of magnesium: implication for anti-migraine action. Magnesium 1985; 4: 169 -1755. Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds.) Neurology in Clinical Practice;2004:20786. Mauskop A, Altura BT, Cracco RQ, Altura BM. V O L .  2 ( 2 )   A P R  -  J U N  2 0 0 7P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  94Table 2: Comparison between mean and standard deviation of VAS at 0.5, 1and 1.5 hours after intervention according to magnesium level of patientsbefore interventionVASGroup of study 0.5 hours after 1 hour after 1.5 hour afterintervention intervention interventionNumber 21 21 21Mean 5.71 3.52 1.57S.D 1.15 1.40 1.08Number 99 99 99Mean 5.70 4.53 3.28S.D 1.16 1.44 1.44Number 120 120 120Mean 5.93 4.35 2.98S.D 1.16 1.48 1.52(P-value = 0.36 for 0.5 hour, P-value = 0.004 for 1 hour, P-value = 0.00 for 1.5 hours aftertrial)Magnesiumless than 1.5mg/dlMagnesiummore than1.5 mg/dlTotalIntravenous magnesium sulfate rapidly alleviates headaches of various  types. Headache 1996; 36:154-60. 7. Mauskop A, Altura BT, Cracco RQ, Altura BM. Intravenous magnesium sulfate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study. Clin Sci 1995; 89: 633-6.8. Ginder S, Oatman B, Pollack M. A prospective studyof I.V. magnesium and I.V. prochlorperazine in the treatment of headaches. J Emerg Med 2000; 18: 311-5.9. Noseworthly JH, Lucchinetti C, Rodriguves M, Weinshemker BG. MS. N Engl J Med 2000; 343: 938-952 10. Thompson WG. Placebos: a review of the placebo response. Am J Gastroenterol 2000; 95: 1637-4311. Bigal ME, Bordini CA, Tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura: a randomized, double-blind, placebo-controlled study. Cephalalgia 2002; 22(5): 345-5312. Boska MD, Welch KM, Barker PB, Nelson JA, Schultz L.. Contrasts in cortical magnesium, phospholipid and energy metabolism between migraine syndromes. Neurology 2002; 58(8): 1227-3313. Demirkaya S, Vural O, Dora B, Topcuoglu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache2001; 41(2): 171-7V O L .  2 ( 2 )   A P R  -  J U N  2 0 0 7P A K I S T A N  J O U R N A L  O F  N E U R O L O G I C A L  S C I E N C E S  95

A Randomized Controlled Study Ofmagnesium Sulfate Versusdihydroergotamine in The Management Ofacute Migraine Attacks

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A Randomized Controlled Study Ofmagnesium Sulfate Versusdihydroergotamine in The Management Ofacute Migraine Attacks

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