Migraines are a common sight during any shift in the ED. I have written about them before, and the benefits of antiemetics and depakote are reasonably well documented. A treatment for refractory headaches that seems to be gaining favor recently is IV magnesium. You may be familiar with Mag and its use in asthma exacerbation, or (gasp) preeclampsia – but emerging evidence suggests that magnesium may help with migraines as well.

How does it work?

In short – no one is 100% sure. In migraine with aura it is thought that magnesium prevents cortical spreading depression – which produces the visual and sensory changes of aura.  It may also alter the release of pain transmitting chemicals in the brain (Substance P and glutamate). Finally, it might prevent serotonin medicated vasoconstriction of cerebral vessels. The narrowing of brain blood vessels caused by the neurotransmitter serotonin.

What’s the dose?

The American Headache Society recommends it as a potential preventative medication at 400-500mg per day. The most common side effect is diarrhea. It may be more effective in migraine with aura and menstrual mediated migraines. The IV dose is 1-2 grams.

What’s the evidence?

Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks
Demirkaya et al
Headache, 2001

The authors conducted a randomized, single-blind, placebo-controlled trial of  30 adults. They were block randomized to the first 15 receiving 1g IV Mag, and the next 15 getting 10 mL of 0.9% saline intravenously.  The placebo patients that still had symptoms in 30 minutes got Mag. They noted that all treatment group patients responded – 13 no pain, 2 diminished. This response rate was statistically significant by Chi Square analysis (P<0.0001). In the placebo group, a decrease in pain was seen – but other symptoms persisted and all 15 eventually got Mag with 14/15 having resolution. Mild side effects were seen in 26/30. This study showed a superiority to placebo as first line, and none had been pretreated.

Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache
Corbo et al
Ann Emerg Med, 2001

A randomized, double-blind, placebo-controlled trial, of 44 adults presenting to 2 urban EDs. They were given either 20 mg of IV metoclopramide plus 2 g of intravenous magnesium sulfate or 20 mg of intravenous metoclopramide plus IV placebo. Meds were given at 15-minute intervals for a max of 3 doses or until pain relief occurred. Each group experienced a more than 50-mm improvement in VAS pain score. The improvement was slightly smaller in the mag group. They also noted that the “number needed to harm with magnesium plus metoclopramide versus metoclopramide alone is 4 patients (95% CI 2 to 36).”

This study is interesting to look at in a vacuum – but it doesn’t apply to current best practice, where antiemetics are first line. nevertheless, concurrent administration with another drug did not seem to be favored.

A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department.
Cete et al
Cephalgia, 2005

This randomized, placebo-controlled, double-blind study of 113 adults comparing 10 mg of IV metoclopramide, 2 g of IV magnesium or normal saline over 10 min. Follow up on pain score was done in the ED and by telephone 24 hours later. Each group experienced more than a 25-mm improvement in VAS score at 30 min – but no significant mean difference between groups. Placebo group patients needed more rescue medications for refractory pain. There were similar recurrence rates at 24 hours.  Ultimately, this study offered additional (albeit weak) support for magnesium.

Intravenous magnesium as acute treatment for headaches: a pediatric case series
Gerstch et al
J Emerg Med, 2014

The authors reviewed 34 EMR records of patients <18 years of age that had received IV Mag. Of note they excluded a large number of patients (14) for complex medical conditions (n = 6), repeat encounters (n = 7) and known secondary etiology for the headache (n = 1). The 20 reviewed charts included 5 patients with migraine, 4 with tension-type headache, and 11 with status migrainosus. 13/20 got Mag in the ED – 7 once admitted. 3/13 ED Mag patients were discharged home – though no statistically significant correlations were established. Obviously further study is warranted.

What about headaches and TBI?

You may have also encountered magnesium as a potential treatment for post traumatic brain injury related headaches as well. Though hypothesized to be neuroprotective, magnesium’s effects post TBI are poorly understood. I would not use it routinely, but if recommended by a subspecialty consultant you can dose as above.