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A 14-year-old girl is seen in an outpatient clinic with a new diagnosis of migraine without aura. She is having at least one episode every week and it is affecting her time in school. Her father has read online that regular high-dose magnesium supplements may be helpful to reduce frequency of migraine. This is not included in local or national guidance, so you decide to research the evidence for benefit.
Structured clinical question
In adolescents (10–18 years) with migraine, with or without aura (population), is the use of high-dose magnesium supplementation (intervention) helpful in reducing the frequency and severity of episodes (outcome)?
MEDLINE via PubMed for primary and secondary sources up to October 2020 using the search terms ‘(magnesium) AND (migraine) AND (adolescent OR teenage OR young OR paediatric)’. Sixty-four results were found, many of which only included an adult population (>18 years of age). Nine papers were considered in detail, and four included (table 1).1
The International Headache Society (IHS) defines migraine as ‘a recurrent headache that occurs with or without aura and lasts for 2–48 hours.’ It is a typical presentation in young people and is in the top five most prevalent long-term conditions in children.2 The onset of migraine tends to last between 15 and 30 min, occurring unilaterally. Exacerbated by physical exercise, its accompanying features include phonophobia, photophobia, vomiting and nausea.2 Patients often describe the headache as moderate to severe in intensity with pulsating features.2
Migraine affects up to 10% of those aged 5–15 years old and up to 28% of those aged 15–19 years old.3 Migraine in children and young people tends to last for shorter periods than in adults and is more likely to present with symptoms such as nausea, vomiting and abdominal pain.3 Paediatric patients with migraine (with or without aura) have been shown to have lower magnesium levels in their saliva, plasma and brain which has been linked to hyperexcitability through the glutaminergic pathway.4 5 There have been studies looking into the effects of magnesium supplementation in adolescents, but these have been variable both in their nature and in their results.
Wang et al in 20036 carried out a double-blind, randomised, placebo-controlled trial, with 118 participants of normal weight presenting with at least weekly moderate-to-severe headache associated with anorexia, nausea, vomiting, photophobia, phonophobia, a pulsatile or throbbing quality, relief with sleep and no fever or evidence of infection. They compared 9 mg/kg of magnesium oxide capsules with placebo for 12–26 weeks. There was a significant decrease in the severity of headache in those treated with magnesium oxide when compared with placebo (p=0.0029) but there was no clear evidence of magnesium being more effective than the placebo in reducing the frequency of headaches over time (p=0.086). Magnesium produced more diarrhoea and/or soft stools (19% vs 7%, p=0.04).6 A further trial was carried out by Gallelli et al 7 who undertook a single-blind, non-randomised, parallel group study of 160 children aged 5–16 years with migraine without aura, diagnosed according to International Classification of Headache Disorders criteria (IHS)8 at least four times per month. Results were reviewed every month for 18 months, comparing paracetamol (15 mg/kg), ibuprofen (10 mg/kg) and magnesium (400 mg/daily) as an adjunct to either. Both paracetamol and ibuprofen induced a significant decrease in pain intensity (p<0.01), with magnesium pretreatment inducing a significant additional decrease in pain intensity (p<0.01) and reduced headache frequency (p<0.01).7 It should be noted that there were no adverse drug reactions in either the paracetamol or ibuprofen groups when in association with magnesium. This could be due to a combination of reasons such as the short time period medication was given over, the safety of the drugs or the absence of additional medications.7
Lower quality cohort studies have also indicated benefits of the use of magnesium. Kovacevic et al 9 carried out a prospective cohort study of 34 young people aged 7–17 years old with migraine diagnosed according to IHS criteria who were treated with oral magnesium oxide or glycinate (4–6 mg/kg per day) for 6 months. They showed an improvement in psychosocial (p≤0.001) and physical well-being scores (p≤0.01) and the anxiety (p=0.004) and depressive (p=0.001) symptoms, along with frequency of migraine episodes reported (p≤0.01). Moscano et al 10 undertook a prospective observational multicentre study of 91 patients using a combination treatment, Partena (a combination of magnesium, coenzyme Q10, vitamin B2, feverfew, parthenolides and Andrographis paniculata), over a 16-week period with a follow-up at week 20 and week 32. Participants, under the care of a paediatrician, had migraine with or without aura or tension-type headache, diagnosed according to IHS criteria, and a headache frequency of at least four times a month for 3 months. Results showed a reduction in frequency of headaches (p<0.01) as well as a lower intensity of pain (p<0.001) in patients with or without aura. The effect was also seen to be maintained after the 16-week period.10 Two low-quality retrospective observational studies by Gertsch et al 11 and Esposito et al 12 reported benefits from other magnesium supplements in the frequency of migraines and pain intensity.
There is some evidence that magnesium may increase the efficacy of other drugs commonly used in migraine, such as paracetamol and ibuprofen, without affecting the toxicity.7 13 However, studies vary in type and dosage and there is a lack of high-quality trials with clear outcomes. Overall, magnesium oxide is a cheaper, safer and generally better tolerated drug than other prescription medications for migraine.6 11 14 Most studies failed to measure plasma magnesium in patients before magnesium administration and, therefore, it was unclear if patients who responded had deficiencies prior to treatment.14 While the administration of magnesium does show positive outcomes compared with placebo, the main role appears to be as an adjuvant therapy that has fewer side effects than the more commonly used migraine preventative therapies.6 12 This is an important consideration, especially in paediatric patients. Further randomised trials are needed to understand the clinical impact of supplementary magnesium, the optimum treatment regimens and the populations in which it may be effective.9–11 Exploring the impact on function and quality of life, taking into account the benefit of improvements to the well-being of patients as well as on the impact on families will be important to assess.
Clinical bottom line
Supplementary magnesium in paediatric patients with migraine disorder may reduce headache frequency and severity (Grade D).
The optimal dosage, duration and route of administration are unclear (Grade D). However, doses of up to 9 mg/kg of magnesium oxide daily, trialled as an adjunctive treatment alongside simple analgesia for 3–6 months, appear well tolerated.
Patient consent for publication
Contributors LE conceived the idea for the topic. JA carried out the literature search and critical analysis and wrote the initial manuscript. Both authors approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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