Statins for Migraine Prevention

Andrea G. Scott, PharmD, MPH


September 12, 2016


For patients who do not respond to first-line migraine prevention treatments, are statins an effective option?

Response from Andrea G. Scott, PharmD, MPH
Pharmacist, Stone Springs Hospital Center, Dulles, Virginia

Migraine headache is a common disorder; about 14% of US adults aged 18 years and older have experienced migraine or severe headache in the previous 3 months. Migraine is about twice as common in females than males (19.1% vs 9%), with the highest incidence occurring in women aged 18-44 years.[1]

Epidemiologic studies estimate that about 38% of patients with migraine need preventive therapy, but few patients (3%-13%) take prophylactic medications.[2] Current migraine prevention guidelines suggest antiepileptic drugs, including divalproex sodium, sodium valproate, and topiramate; and beta-blockers, including metoprolol, propranolol, and timolol, as first-line agents for migraine prevention. Frovatriptan is recommended for menstrually associated migraine.[3] Statin drugs are not recommended or mentioned in current guidelines.

The potential use of statins for the prevention of migraine was first proposed in a case report a decade ago. A 58-year-old man was prescribed atorvastatin 20 mg daily for hypercholesterolemia. He had a history of recurrent typical aura with migraine (approximately two episodes per month) since he was 20 years old. After he began statin therapy, his migraine attacks disappeared.[4]

An open-label study followed with propranolol 60 mg daily in women with more than six migraine attacks per month and simvastatin 20 mg in women with hyperlipidemia and more than six migraine attacks per month. Both drugs had a high efficacy (possibly owing to factors such as high expectation for cure); the response rate for propranolol was 88% with a 50% decrease in attacks and 83% for simvastatin.[5]

A cross-sectional population study of nearly 6000 people found that statin use was associated with a lower prevalence of severe headache or migraine (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.46-0.98; P=.04). When the variable of vitamin D status was analyzed, statin use among participants who had a serum 25-hydroxy vitamin D level >57 nmol/L (22.8 ng/mL) had a much lower risk for severe headache or migraine with an adjusted OR of 0.48 (95% CI, 0.32-0.71, P=.001), while no association was found with people with lower vitamin D levels.[6]

A double-blind, controlled study randomly assigned 57 adults with episodic migraine to either simvastatin 20 mg twice daily plus vitamin D3 (cholecalciferol) 1000 IU twice daily or identical placebo for 24 weeks. In the simvastatin/vitamin D group, eight patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and nine patients (29%) at 24 weeks; only one patient (3%) in the placebo group experienced a reduction in migraine days (simvastatin/vitamin D vs placebo, P=.03).[7]

Statins have pleiotropic effects in addition to antihyperlipidemic effects that may play a role in reducing migraine attacks. Statins may reduce migraine attack frequency by improving endothelial function, arterial stiffness, and vascular tone. Other actions, such as reducing inflammatory responses and decreasing platelet aggregation and thrombosis, also could contribute to the beneficial effect on migraine.[6]

For patients who do not respond to first-line migraine prevention treatments, a statin might be worth a try based on limited evidence and a good safety profile. Some evidence suggests that statins might be more effective with adequate vitamin D levels, so determining adequacy of vitamin D would be a reasonable first step. If a statin is indicated for a condition other than migraine, ask the patient if the statin has affected the frequency of migraine. Whether one statin is more effective than another for migraine is unknown. More research is required in larger numbers of patients to establish the place of statins in migraine prevention.

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