Melatonin

Summary:
Melatonin is a neurohormone involved in circadian rhythm regulation. Supplementation may reduce migraine frequency, particularly in those with sleep disturbance.

Biological Plausibility

Melatonin influences pain processing, sleep, and hypothalamic function—all relevant to migraine biology. It also has antioxidant properties.

Evidence

RCTs show 3 mg nightly is as effective as amitriptyline for migraine prevention, with better tolerability and fewer side effects.

Effect Size

Comparable to older preventive medications (1–2 fewer migraine days/month).

⚠️ Risk

Minimal. Rare side effects include drowsiness or vivid dreams.

Cost

$

Scores

• Benefit: 3
• Burden: 2
• Ratio: 1.5

Clinical Takeaways

• Safe and well-tolerated preventive option.
• Best for patients with sleep irregularities or circadian disruption.
• Use consistently at the same bedtime for best results.

Key References

• Peres MF, et al. *Melatonin, 3 mg, is effective for migraine prevention.* J Neurol Neurosurg Psychiatry. 2004.
• Leone M, et al. *Melatonin versus amitriptyline for migraine prevention: a randomized controlled trial.* J Neurol. 2016.