Within the two months of intervention, atorvastatin at dose of 20 mg/day showed a significant reduction in the number of migraine attacks. Furthermore, treatment with atorvastatin at this dose was associated with significant improvement in pain severity during the 8 weeks of clinical trial. Most adverse effects experienced by the patients in both arms were mild and tolerable and no specific side effect was observed during the study. The number of patients experiencing adverse effects were slightly higher in intervention group, although this difference did not reach a statistical significance.
Addition of atorvastatin in migraineurs’ preventive regimen was associated with a responder rate of 65% during the two months of study and a mean reduction of 3 migraine attacks per month. These amounts in previous studies were 50% for propranolol(32), amitriptyline(33), sodium valproate and divalproex and 40% for candesartan(34). Patient satisfaction, as an indicator of quality care, was significantly higher in intervention group. This could be attributed to the reduced number of migraine attacks following the addition of atorvastatin to the treatment.
Some studies have shown that migraine patients may suffer from endothelial dysfunction of cerebral, coronary, retinal, dermal and peripheral vasculature(35). They believe that migraine is originated from neurologic inflammation in central nervous system. Migraineurs may have impaired endothelium dependent function and an underlying systemic vasomotor abnormality(36). They have a diminished endothelium-dependent vasodilatation capacity compared with healthy-participants. Therefore, statins with their proven improving effects on endothelial and vasomotor function, attenuating oxidative stress and inflammatory cytokines in central brain, and neuronal protection could be beneficial in prevention of migraine headache(37). Atorvastatin, the most commonly used drug among statins, suppresses nuclear factor κB pathway in trigeminal nucleus, which has a critical role in pathogenesis of migraine in recent studies(38–40).
A recent study has shown that atorvastatin is as effective and safe as sodium valproate in preventing migraine attacks. They believed that this may contributed to antinociceptive, anti-inflammatory and antioxidant effects of statins. Moreover, administration of this medication was not accompanied by any specific adverse effects in patients(41). In a case report, it was indicated that initiation of atorvastatin at dose of 20 mg/day for a patient with frequent attacks of typical migraine completely resolved migraine attacks(42). In another study, it was reported that twice daily consumption of 1000 international units’ vitamin D3 and 20 mg of simvastatin for 12 weeks significantly reduced the number of migraine attacks in patients with more than 10 years history of migraine(43). However, their study design could not differentiate between an effect of statin alone, or vitamin D alone, or the combination of both of them. However, in the present study, an interval of at least one month was set to correct and obtain a normal serum level of vitamin D3 before allocation into study arms. Therefore, the possible effect of vitamin D was diminished.
In a study by Pahan et al, it was shown that statins induce iNOS expression, upregulate endothelium nitric oxide synthase, which result in increased nitric oxide levels(44). This may offset the diminished vasodilatation capacity of our patients and explain the decreased number of migraine attacks and their severity observed in our intervention group. It seems that atorvastatin prevents migraine attacks by improving the vasomotor performance in cerebral vessels(45, 46).
Although the results of the present study were so promising with predefined endpoints and controlled triple blinded trial manner, these findings should be confirmed in larger groups of migraineurs with longer duration of follow-up to optimize the best dose of atorvastatin and optimal period of treatment with Atorvastin for complete prevention of migraine headache and migraine attacks.