Statins and vitamin D for migraines

First there is the intense throbbing and pulsating headache on the one side of your head, then the nausea sets in and you want to throw up. Your vision goes blurry, and you are very sensitive to lights and sounds.

Yes – it is another migraine attack, and all you want to do is curl up in a dark room and go to sleep until it is all over. Migraines rank as one of the top 10 highest causes of disability in the world. The experience and frequency of the migraines vary depending on the person. Some migraine attacks can last days if untreated. Migraines tend to increase in frequency and intensity over time, and many people require pharmacological management to both prevent, and to stop / provide relief from them.

Prevention

Prevention of migraines is the preferred approach, and includes avoiding or managing triggers, but often there are no obvious causes for triggering the migraine. Pharmacological management is considered when someone experiences two or three severe migraines each month, which significantly impacts on their quality of life, and they do not respond to treatment taken at the onset of the migraine.

Unfortunately, medicines used for preventing migraines show moderate efficacy at best, and are associated with significant adverse effects. Also, these medicines are often used ‘off-label’ for migraine prevention. Beta-blockers (block beta-adrenergic receptors), and amitriptyline (inhibit reuptake of noradrenaline and serotonin) are the first drugs of choice.

The antiepileptic medicines valproate (blocks voltage- and use-dependent sodium channels, enhances gamma-Aminobutyric acid (GABA) activity, and inhibits glutamate and blocks T-type calcium channels), and topiramate (block voltage-gated sodium channels to stabilise presynaptic neuronal membranes, and enhances GABA activity) are used as second line-therapy.

Other drugs have limited evidence supporting their use e.g. gabapentin, cyproheptadine, clonidine; or the adverse effects restrict their usefulness e.g. pizotifen. Botulinum toxin is also marketed for use as migraine prophylaxis in some people, and requires advice of a specialist.

Statins

There is still a need for a medicine which can effectively prevent migraines. Interestingly, an epidemiological study observed fewer migraines were experienced by people taking statins, but only if they had calcifediol (a metabolite used for measuring vitamin D status) levels above 57 nmol/L.

While statins are most famous for their cholesterol-lowering effects, they are also known to improve endothelial dysfunction, reduce vascular wall inflammation, decrease platelet aggregation, and may improve the autonomic function and sympathetic reflex regulation.

It is proposed that Vitamin D synergistically augmented the statins’ anti-inflammatory effects, and improved endothelial function.

A randomised, double-blinded, placebo-controlled trial compared the incidence of migraines in 57 adults when taking 20 mg simvastatin and vitamin D3 1000 international units (IU) twice daily. Participants remained on their migraine prophylaxis and treatment medicines.

The study started with a 12-week baseline period (week -12 to 0), followed by a 24 week intervention period (1–12, and 13–24), where participants received the twice daily simvastatin and vitamin D3. Compared to placebo, there was a significantly greater reduction in the number of migraine days from the baseline period, to week 1–12 of the intervention period (-8.0 versus +1.0; p < 0.001), and week 13–24 (-9.0 versus +3.0; p < 0.001). As a secondary outcome, participants in the active arm also used significantly less of their migraine treatment medicines during the intervention periods compared to the baseline period.

Adverse effects were similar between the two arms of the study. While these findings are promising, much more work is required in a larger population with more diverse characteristics, to better ascertain if and where simvastatin and vitamin D3 belong in the management options for migraines.

Nevertheless, this combination of medicines holds promise as an effective and well tolerated option for preventing migraines.

Simvastatin and Vitamin D3 dosing information

*Vitamin D and simvastatin do not have an indication for this condition – dose provided is indicative only.

DR ESTHER LAU MPS School of Clinical Sciences, Queensland University of Technology, Brisbane

PROF LISA NISSEN FPS School of Clinical Sciences, Queensland University of Technology, Brisbane

Useful references

1. Buettner C, Nir RR, Bertisch SM, Bernstein C, Schain A, Mittleman MA, Burstein R. Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Ann Neurol. 2015;78(6):970–81.
2. Buettner C, Burstein R. Association of statin use and risk for severe headache or migraine by serum vitamin D status: a cross-sectional population-based study. Cephalalgia 2015;35(9):757–66.