What is the role of magnesium in treating headaches?

Magnesium in Headache Treatment

Oral magnesium is recommended for migraine prevention, while intravenous magnesium sulfate provides rapid relief for acute migraine attacks, particularly in patients with low serum ionized magnesium levels.

Role in Migraine Prevention

The 2023 VA/DoD guidelines suggest oral magnesium for the prevention of migraine with a weak recommendation based on consistent evidence 1. This recommendation has remained stable across multiple guideline iterations, reflecting sustained support despite the evidence quality being modest 1.

Mechanism and Rationale

• Magnesium deficiency promotes cortical spreading depression, alters neurotransmitter release, and increases platelet hyperaggregation—all implicated in migraine pathogenesis 2.
• Magnesium acts as an important cofactor for enzymatic reactions and plays a critical role in neurochemical transmission and muscular excitability 3.

Preventive Dosing Strategy

• Start oral magnesium supplementation for patients with ≥2 migraine attacks per month producing disability lasting ≥3 days per month 1.
• The evidence supports oral magnesium as a simple, inexpensive, safe, and well-tolerated preventive option 2.
• Allow 2-3 months at therapeutic dosing before declaring treatment failure, as clinical benefits may not become apparent immediately 4.

Position in Treatment Algorithm

Oral magnesium ranks among other weak-for recommendations including topiramate, propranolol, and valproate for episodic migraine prevention 1. It sits below strong recommendations for CGRP antagonists (erenumab, fremanezumab, galcanezumab) and ARBs (candesartan, telmisartan) 1.

Role in Acute Migraine Treatment

Intravenous magnesium sulfate (1 gram over 15 minutes) provides rapid relief for acute migraine attacks, particularly effective in patients with documented low serum ionized magnesium levels 5, 6, 7.

Acute Treatment Efficacy

• Complete pain elimination occurs in 80-87% of patients within 15 minutes of IV magnesium sulfate infusion 5, 6.
• Pain relief persists for at least 24 hours in 56-86% of responders 5, 6.
• Meta-analysis confirms significant relief at 15-45 minutes, 120 minutes, and 24 hours post-infusion 8.

Patient Selection for IV Magnesium

• Patients with serum ionized magnesium levels below 0.54 mmol/L show 86% sustained response rates compared to only 16% in those with normal levels 7.
• Consider measuring serum ionized magnesium (not total magnesium) to identify optimal candidates, as total magnesium levels remain normal even when ionized levels are deficient 6, 7.
• Cluster headache patients exhibit the lowest basal ionized magnesium levels and may be particularly responsive 6.

IV Administration Protocol

• Administer 1 gram of magnesium sulfate intravenously over 15 minutes for acute attacks 5, 6.
• Onset of anticonvulsant action is immediate with IV administration, lasting approximately 30 minutes 3.
• Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/L 3.

Safety Profile

• Side effects are mild and well-tolerated: brief flushing sensation, warmth, and mild sweating occur in approximately 87% of patients but do not necessitate discontinuing treatment 5, 6.
• At low doses, magnesium produces only flushing and sweating; larger doses may lower blood pressure 3.
• Magnesium is excreted solely by the kidneys, requiring caution in renal impairment 3.

Critical Clinical Pitfalls

• Do not rely on total serum magnesium levels—they remain normal even when ionized magnesium is deficient 6, 7. Measure ionized magnesium specifically to identify deficiency states.
• Non-responders to IV magnesium often have normal or elevated ionized magnesium levels 6, 7. Consider alternative acute treatments (triptans, NSAIDs) in these patients 1.
• Avoid premature discontinuation of oral magnesium prophylaxis—allow the full 2-3 month trial period before declaring treatment failure 4.
• IV magnesium eliminates migraine-associated symptoms (photophobia, phonophobia, nausea) in addition to pain 5, 6.

Comparison to Other Treatments

While current guidelines place stronger emphasis on triptans for acute treatment 1 and CGRP antagonists or ARBs for prevention 1, magnesium offers unique advantages: it can be used during pregnancy, in patients with cardiovascular disease where triptans are contraindicated, and provides a low-cost option with minimal side effects 2, 5.

The 2002 guidelines noted insufficient evidence for several supplements (coenzyme Q10, feverfew, vitamin B2) 1, but magnesium has maintained consistent support across guideline updates through 2023 1.