Intravenous magnesium sulfate rapidly alleviates headaches of various types.

Background: Circumstantial evidence points to the possible role of magnesium deficiency in the pathogenesis of headaches and has raised questions about the clinical utility of magnesium as a therapeutic regimen in some headaches.

Methods: We evaluated the efficacy of intravenous infusion of 1 gram of magnesium sulfate (MgSO4) for the treatment of patients with headaches and attempted to correlate clinical responses to the basal serum ionized magnesium (IMg2+) level. We also determined if patients with certain headache types exhibit low serum IMg2+ as opposed to total serum magnesium. Using a case-control comparison at an outpatient headache clinic, a consecutive sample of patients presenting with a moderate or severe headache of any type were included in the study. Of the 40 patients in the study (mean age 38.2 +/- 9.4 years; range 14 to 55; 11 men [39.2 +/- 7.3 years] and 29 women [37.8 +/- 10.2 years]), 16 patients had migraines without aura, 9 patients had cluster headaches, 4 patients had chronic tension-type headaches, and 11 had chronic migrainous headaches. Total serum magnesium was measured with atomic absorption spectroscopy and a Kodak Ektachem DT-60. Sensitive ion selective electrodes were utilized to measure serum IMg2+ and ionized calcium (ICa2+); ICa2+/IMg2+ ratios were calculated.

Results: Complete elimination of pain was observed in 80% of the patients within 15 minutes of infusion of MgSO4. No recurrence or worsening of pain was observed within 24 hours in 56% of the patients. Patients treated with MgSO4 observed complete elimination of migraine-associated symptoms such as photophobia and phonophobia as well as nausea. Correlation was noted between immediate and 24-hour responses with the serum IMg2+ levels. Immediate pain relief was observed in 32 (80%) of 40 patients (P < 0.001). In 18. of the 32 patients, pain relief persisted for at least 24 hours (P < 0.005). Of these 18 patients, 16 (89%) had a low serum IMg2+ level. Total magnesium levels in contrast in all subjects were within normal range (0.70-0.99 mmol/L). No side effects were observed, except for a brief flushed feeling. Of the 8 patients with no relief, only 37.5% had a low IMg2+ level. Patients demonstrating no return of headache or associated symptoms within 24 hours of intravenous MgSO4 exhibited the lowest initial basal levels of IMg2+. Non-responders exhibited significantly elevated total magnesium levels compared to responders. Although most subcategories of headache types investigated (ie, migraine, cluster, chronic migrainous) exhibited low serum IMg2+ during headache and prior to intravenous MgSO4, the patients with cluster headaches exhibited the lowest basal levels of IMg2+ (P < 0.01). All headache subjects except for the chronic tension group exhibited rather high serum ICa2+/IMg2+ ratios (P < 0.01, compared to controls).

Conclusions: Intravenous infusion of 1 gram of MgSO4 results in rapid relief of headache pain in patients with low serum IMg2+ levels. Measurement of serum IMg2+ levels may have a practical application in many types of headache patients. Low serum and brain tissue ionized magnesium levels may precipitate headache symptoms in susceptible patients.