Name: Angelika Dabu
Evidence-Based Medicine Mini-CAT
Clinical Question:
28 y/o female presents c/o menstrual migraines without aura that have worsened over the last few months. The patient admits to taking Advil but states the migraines have become more severe and are no longer relieved by ibuprofen.
Would the administration of magnesium be more effective in relieving her migraines?
PICO Question:
P: Women with menstrual migraine, women of reproductive age, otherwise healthy women
I: Administration of magnesium, oral and IV
C: No intervention
O: Decreased severity of menstrual migraines, decreased frequency of menstrual migraines, adverse reactions or effects, no change in severity or frequency in menstrual migraines
Search Strategy:
PICO Search Terms
| P | I | C | O |
| Menstrual migraine | Magnesium | No intervention | Decreased severity |
| Women with migraines | Oral magnesium | Decreased frequency | |
| Young women | IV magnesium | No change or effect | |
| Efficacy | |||
| Prophylaxis | |||
| Relief |
PubMed: 109
GoogleScholar: 242
Cochrane Library: 8
Articles Chosen for Inclusion:
Selected articles: Within the past five years
Menstrual Migraine and Treatment Options: Review
Objective. A review of treatment options for menstrual migraine.
Background. Migraine affects 30 million people in the US. A subset of female migraineurs have migraines that are mainly associated with menstruation. Menstrual migraine (MM) is divided into pure MM and menstrually related migraine. Pure MM attacks occur only with menstruation and have a prevalence of 1%. Menstrually related migraine has a prevalence of 6-7%, and occurs both during menstruation as well as during the rest of the cycle. MM is usually without aura and is more severe, longer lasting, and more resistant to treatment due to the effects of ovarian hormones, specifically estrogen. MM treatment is divided into acute, short-term prophylaxis, and daily prevention. The best-studied acute treatments are triptans. For short-term prophylaxis, triptans, non-triptans, or combinations are used. Some preventive medications may be used daily to prevent MM. Many anti-epileptic medications used in migraine prevention can affect the efficacy of oral contraceptives and hormonal treatments, so caution is indicated when these are used.
Methods. PubMed, Scopus, Cochrane, and Embase were searched for MM and treatments.
Results. Many randomized, placebo-controlled, prospective studies have evaluated the efficacy of sumatriptan, rizatriptan, naratriptan, zolmitriptan, and almotriptan in MM. Reviewing numerous studies with statistically significant results, rizatriptan has the best overall evidence for acute treatment of MM, ranging from pain-free responses of 33-73% at 2 hours. Sumatriptan and rizatriptan have shown similar efficacies of 61-63% in terms of 2 hour pain freedom. Rizatriptan showed sustained pain relief between 2 and 24 hours with an efficacy of 63% and sustained pain freedom for MM between 2 and 24 hours with an efficacy of 32%. For short-term prevention of MM, there were four randomized controlled trials for frovatriptan taken twice daily, one trial for zolmitriptan taken three times daily, and two studies for naratriptan taken twice daily, all of which showed statistically significant results. Among studies
on non-triptans for short-term prevention of MM, magnesium, estrogen, naproxen sodium, and dihydroergotamine all had statistically significant results. Many antiepileptic medications taken for prevention of MM can cause enzyme induction affecting oral contraceptives (OCs) and hormonal treatments to different degrees. Topiramate has the least effect on OCs at doses below 200 mg/day.
Lamotrigine noticeably decreases oral contraceptive levels; however, the evidence for it as a preventive medication is not strong.
Conclusion. MM can be very difficult to treat. For acute treatments, rizatriptan has the best overall evidence. For short-term prevention, frovatriptan, zolmitriptan, or naratriptan, as well as magnesium, estrogen, naproxen sodium, or dihydroergotamine may be useful.
Key words: menstrual migraine, menstrually related migraine, prophylaxis, hormones, estrogen
Magnesium in the gynecological practice: a literature review.
Abstract. A growing amount of evidence suggests that magnesium deficiency may play an important role in several clinical conditions concerning women health such as premenstrual syndrome, dysmenorrhea, and postmenopausal symptoms. A number of studies highlighted a positive correlation between magnesium administration and relief or prevention of these symptoms, thus suggesting that magnesium supplementation may represent a viable treatment for these conditions. Despite this amount of evidence describing the efficacy of magnesium, few and un-systematize data are available about the pharmacological mechanism of this ion for these conditions. Herein, we review and systematize the available evidence about the use of oral magnesium supplementation in several gynecological conditions and discuss the pharmacological mechanisms that characterize these interventions. The picture that emerges indicates that magnesium supplementation is effective in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine and in the prevention of climacteric symptoms.
Key words: magnesium, dysmenorrhea, menopause, premenstrual symptoms
The efficacy of different oral magnesium supplements for migraine prevention: a literature review.
ABSTRACT
No study was conducted to evaluate the efficacy of particular oral magnesium supplement over another in preventing migraine. Different magnesium supplements have different oral absorption and bioavailability. The objective was to identify the efficacy of different oral magnesium supplements in migraine prophylaxis. A literature review using MEDLINE, Scopus, Cochrane library, and EMBASE was conducted during the period from November 1, 2015 until December 30, 2015. Magnesium citrate was used as single oral migraine prophylactic supplement in most of the published trials. Migraine attack frequency and intensity were significantly lower in magnesium citrate group compared to placebo with 41.6-64% and 43-59% reduction in migraine attack frequency and severity frequently. Magnesium oxide was used in combination with magnesium citrate in 2 randomized clinical trials (RCTs), and used alone in one RCT in adults and children. No different in migraine frequency or severity between Mg-oxide and placebo in RCT conducted in children while Only Mg-oxide containing groups showed significant reduction in migraine days when compared to control (p<0.006) in RCT conducted in adults. Magnesium chloride had never introduced as migraine prophylactic agent in clinical trials. Magnesium citrate seems to be the preferred oral magnesium supplement for migraine prevention; however, further studies comparing the efficacy of different oral magnesium supplements are needed.
Key words: magnesium, migraine, prophylaxis, efficacy, oral supplements
The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study
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 inal 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.
Keywords: Migraine headache · Magnesium oxide · Valproate sodium · Clinical trial · Crossover
Summary of the Evidence:
| Author (Date) | Levelof Evidence | Sample/Setting(# of subjects/ studies, cohort definition etc. ) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Maasumi, Kasra, Tepper, Stewart J., and Kriegler, Jennifer S. (2016) | Narrative Review | Evidence-based randomized placebo-controlled, prospective studies from PubMed, Embase, Google Scholar, Cochrane and Scopus with dates ranging from 1970 to 2016 | Efficacy of acute treatment and short-term prevention with triptans and non-triptans | Rizatriptan was found to be the most effective agent as acute treatment for menstrual migraine while frovatriptan produced the most benefit in terms of short-term prophylactic treatment.For short-term prevention with non-triptans, estrogen and naproxen were found to be beneficial.Magnesium was found to be beneficial but to a lesser degree. | Some studies are old dating back to 1970. Studies had different definitions of menstrual migraine with some having further divided menstrual migraine into menstrually related migraines and pure menstrual migraines.For acute treatment options, studies were inconsistent in terms of primary outcome measures. Some involved 2 hour pain relief while others involved 2 hour pain free, 2- to 24- hours pain relief or 2- to 24-hour pain free. |
| Parazzini, Fabio, Di Martino, Mirella, and Pellegrino, Paolo (2017) | Literature/Systematic Review | Placebo-controlled studies and parallel trials | The efficacy and role of oral magnesium in a gynecological setting with respect to premenstrual syndrome, dysmenorrhea, and postmenopausal disorders. | The administration of oral magnesium is efficacious in the prevention of dysmenorrhea, premenstrual syndrome, and menstrual migraine. More specifically, oral magnesium was found to have a 41.6% reduction in the frequency of migraine attacks compared to a 15.8% reduction in the placebo group. | Emotional and physical stressors, which were discussed as important aspects of migraine onset, were not explored. Conflict of interest: Dr Pellegrino is currently undergoing an internship at Sanofi; Dr Parazzini received a grant from Sanofi for public speaking. |
| Alghadeer, Sultan M. (2016) | Literature Review | Randomized clinical trials published between 1985 and 2015 found using MEDLINE, Scopus, Cochrane library and EMBASE with the quality of the trials assessed using Jadad scores ranging from 0 to 5, high quality scores being 3-5 points and low quality scores being 0-2 points. | The efficacy of various oral magnesium supplements in migraine prophylaxis in terms of frequency and intensity | In a study that compared magnesium pyrrolidone carboxylic acid to a placebo with respect to menstrual migraines, magnesium pyrrolidone carboxylic acid showed reductions in intensity and duration of migraines. In a study that compared magnesium citrate to a placebo, the frequency and intensity of migraine attacks were much lower in the magnesium citrate group.In a study that compared magnesium oxide to a placebo as prophylaxis, the frequency of migraine was much lower in the magnesium group. | Different dosages of magnesium were used among the RCTs.One of the RCTs was conducted in a pediatric population between 3-17 years old.Only one study focuses specifically on menstrual migraines as opposed to migraines on a general scale. Findings may be questionable as many of the studies are old and use different outcome measures to evaluate migraine frequency and severity. |
| Karimi, Narges, Razian, Azadeh, and Heidari, Mohammad. (2019) | Randomized, Controlled, Double-blind Crossover Study | Single-center, randomized, controlled, crossover trial that is double-blind, 24-week, 2-sequence, 2-period, 2-treatment conducted in Iran. Participants were between 18-65 years old. | The efficacy of magnesium oxide versus the efficacy of sodium valproate in migraine prophylaxis. | No significant difference was found between magnesium oxide and sodium valproate as both lead to significant decreases in the number, duration and intensity of migraine after treatment. | The study was not specific to menstrual migraines and included participants well over reproductive age.The study also lacked a placebo control. |
Conclusion(s):
While research has found there is magnesium deficiency in menstrual migraine, few studies have been conducted to comprehensively evaluate the effect of magnesium as treatment for menstrual migraines though results at present show statistical significance.
Clinical Bottom Line:
There is limited evidence on the efficacy of magnesium as a single treatment for menstrual migraines alone. Further studies are needed to better understand the effectiveness of magnesium in both oral and intravenous forms to treat and prevent menstrual migraines.
References:
Maasumi, K., Tepper, S.J. and Kriegler, J.S. (2017), Menstrual Migraine and Treatment Options: Review. Headache: The Journal of Head and Face Pain, 57: 194-208. doi:10.1111/head.12978
Parazzini F, Di Martino M, Pellegrino P. Magnesium in the gynecological practice: a literature review. Magnesium research. 2017;30(1):1-7. doi:10.1684/mrh.2017.0419.
Alghadeer, Sultan M. The efficacy of different oral magnesium supplements for migraine prevention: a literature review. Indonesian Journal of Pharmacy, Vol. 21 No. 3: 174-182. ISSN-p:2338-9427.
DOI: 10.14499/indonesianjpharm27iss3pp174
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 (2019). https://doi-org.york.ezproxy.cuny.edu/10.1007/s13760-019-01101-x
