migraine prophylaxis with simvastatin/vitamin D

A small research study found that using the combo of simvastatin 20mg plus vitamin D3 1000 IU bid led to decreased migraine recurrences (see migraine prevention simv vit d annneurol2015 in dropbox, or Ann Neurol 2015;78:970​). The basis for this study was that the usual treatments (anticonvulsants, b-blockers, tricyclics) often have problematic adverse effects, and that migraines may involve a component of endothelial dysfunction/vascular inflammation which may improve with a statin and vitamin D. details:

--57 patients with migraine diagnosis and at least 4 migraine-days/month were randomized (mean age 40 in active treatment/28 in placebo!!; 90% women; 4% current smoker; 40% with seasonal allergies; 40% anxiety/depression; 50% on oral contraceptives; 50% on current migraine prevention meds).  most had migraines >10 years and had tried median of 3 abortive agents in the past. note that in this small study, many of these %'s differed from the active med vs placebo groups (eg, number of migraine days was 25.5 in the past 3 months in the active med group but only 18 in the placebo group). those on migraine prophylactic agents continued taking them. followed 24 weeks

--primary outcome: change in number of days with migraine; secondary outcome: changes in use of acute migraine meds, and migraine disability/duration/intensity/associated symptoms

--results:

    ​--primary outcome: those on active treatment in the first 12 weeks had a decrease of 8 migraine-days (-15.0 to -2.0) vs +1.0 in the placebo group (-1.0 to +6.0), with p<0.001. during the second 12 weeks, there were similar improvements: -9.0 days with active treatment (-13 to -5) vs +3.0 with placebo (+1.0 to +5.0) with p<0.001. And, 29% of those on active meds had >50% reduction in migraine-days vs 3% on placebo

    --secondary outcomes: those on active meds: used fewer abortive migraine meds, and had both fewer days of meds (p<0.001)and fewer doses of meds (p<0.001); less migraine disability (p<0.001); but no difference in symptoms when migraines did occur, nor of migraine severity/duration/symptoms

    --there were similar reductions in migraine in those continuing with their other prophylactic meds or not

    ​--regression analysis showed no difference in response by baseline values, including age and BMI, or if baseline < vs >8 migraine-days/month

    --adverse events: very few, nonsignficant differences (though interesting that there were more myalgias in the placebo group as well as joint/skeletal pain)

so, a few points:

--the magnitude of this treatment effect (30% fewer migraine-days) exceeds that of many of the other drugs currently used clinically (though actually hard to compare the studies since different study designs)

--the simvastatin/vitamin D was really well-tolerated, vs the reported 25-50% range discontinuance rates reported for amitryptaline, topiramate, and propranolol.

--clearly this was a small and preliminary study. but the results were pretty impressive, for meds that are used all the time​ for other indications, are well-tolerated, and may even have other benefits (vitamin D and bone/?immunologic function; statins and atherosclerosis prevention). Though a bigger study is necessary to confirm the above, I think it is reasonable to try simvastatin/vitamin D in patients with frequent migraine with either minimal response or too many adverse effects of the standard prophylactic meds (and I wonder if combos of this with other meds might be even more effective, since they likely have different  mechanisms of action).