Non-traumatic headaches comprise up to 4% of all emergency department (ED) visits. Current practice is moving toward multimodal analgesia regimens that limit narcotic use.The objective of this systematic review is to address the following research question: In patients with non-traumatic headaches (Population), does administration of intravenous magnesium sulfate (Intervention) compared to placebo, corticosteroids, dopamine antagonists, ergot alkaloids, non-steroidal anti-inflammatory drugs (NSAIDs), triptans, or usual care result in better pain control, lower rate of recurrence at 24 hours, lower requirements for rescue analgesia, and less adverse medication effects (Outcomes)?Scholarly databases and relevant bibliographies were searched, as were clinical trial registries and relevant conference proceedings to limit publication bias. Studies were not limited by date, language, or publication status. Inclusion criteria were: (1) randomized clinical trial (RCT), (2) patients age ≥18 years, (3) non-traumatic headache, (4) patients treated in ED or an outpatient acute care treatment center, and (5) magnesium sulfate administered intravenously (IV). Eligible comparison groups included: placebo, conventional therapy, dopamine antagonist, NSAID, corticosteroid, ergot alkaloid, or triptans.Out of 4018 identified references, 7 RCTs (545 participants) that treated migraine headaches (n = 6) and benign non-traumatic headaches (n = 1) met inclusion criteria. Pain intensity was improved with magnesium sulfate vs comparators at 60-120 minutes, but not at earlier time points. Result for the endpoint of pain reduction by 50% were conflicting as 3 studies reported that headache was improved, unchanged, and less with magnesium sulfate. Complete pain relief was improved with magnesium sulfate in 1 study, and in the migraine with aura (MA) subgroup in another. The need for rescue analgesia at any point was improved with magnesium sulfate in 1 study, and in the MA subgroup in another. Twenty-four-hour headache recurrence was improved with magnesium sulfate in 1 study, but unchanged in a second. The intended meta-analysis was not performed due to the clinical heterogeneity among studies.While we cannot draw a firm conclusion on the efficacy or benefit of intravenous magnesium sulfate in the treatment of acute non-traumatic headaches, the existing evidence indicates potential benefits in pain control beyond 1 hour, aura duration, and need for rescue analgesia.
