Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache

Study objective: We test the hypothesis that intravenous magnesium sulfate is an effective adjunctive medication for treatment of acute migraine. Methods: In this randomized, double-blind, placebo-controlled trial, adults presenting to 2 urban emergency departments with headache meeting Internat ional Headache Society criteria for acute migraine received either 20 mg of intravenous metoclopramide plus 2 g of intravenous magnesium sulfate or 20 mg of intravenous metoclopramide plus a placebo of intravenous saline solu tion at 15-minute intervals for a maximum of 3 doses or until pain relief o ccurred. At 0, 15, 30, and 45 minutes, patients recorded pain intensity usi ng a standard visual analog scale (VAS). The primary study end point was th e between-group difference in pain improvement when initial and final VAS s cores were compared. Results: Of 44 patients enrolled (21 randomized to metoclopramide plus magn esium and 23 to metoclopramide plus placebo), 42 (95%) were women. Baseline features were comparable in both groups. Each group experienced a more tha n 50-mm improvement in VAS score during the study. However, this improvemen t was smaller in the magnesium group for the primary end point (16-mm diffe rence favoring placebo [95% confidence interval (CI) -2 to 34 mm]), as was the proportion with normal functional status at their final rating (36% abs olute difference also favoring placebo [95% Cl 7% to 65%]). Using a 50% red uction in pain to dichotomize VAS scores, the number needed to harm with ma gnesium plus metoclopramide versus metoclopramide alone is 4 patients (95% Cl 2 to 36). Conclusion: Although this result was unexpected, our data suggest that the addition of magnesium to metoclopramide may attenuate the effectiveness of metoclopramide in relieving migraine. Counter therapeutic cerebral vasodila tation caused by magnesium is a plausible, although unproven, explanation f or this finding. Because of the preponderance of women in our trial, these data may not be generalizable to men.