NIH funding for research on headache disorders: does it matter?

Migraine disorders and the epilepsies have much in common. Both are highly prevalent paroxysmal neurological disorders that have peak incidence prior to adulthood and may be life-long. They are also often co-morbid. Both appear to share important pathogenic mechanisms involving the same genes and electrophysiological events, and they are often responsive to the same medications.1 Both are associated with huge economic costs and profound disabilities. While prolonged seizures may be fatal, the far higher prevalence of migraine leads to >85% more lost years annually from death or disability than the epilepsies.2 Given the close parallels between these disorders, why then, over the past 15 years, have 10 new medications been FDA-approved for the treatment of epilepsy, whereas only 1 new medication (plus 6 “metoo” drugs) has been approved for migraine (Table)? One possibility is that research efforts have been similarly aggressive for both groups of disorders but that comparatively more migraine trials failed. It is also conceivable that fewer headache clinical trials were performed due to a lack of interest on the part of the pharmaceutical industry, though this is unlikely given the enormous size of the migraine market. Regardless, these possibilities are beyond investigation given the absence of a comprehensive national registry of clinical trials. There is, however, a much more plausible and simple explanation for the discrepancy in drug approvals: there were fewer promising compounds available to test in migraine clinical trials. Why might this be so? Abundant evidence shows that the seminal studies that lead to innovative pharmaceuticals are most often performed in publicly funded research laboratories, not those of the pharmaceutical industry.3 Federal funding of research on epilepsy has always hugely outpaced that for migraine. Over the past several years, mean annual NIH expenditures for epilepsy have been ∼$101M4 compared to ∼$13M5 for migraine, with a comparable disparity in funding every year since 1972 — the earliest year of available records for NIH grants (Figure). What did the federal funding for epilepsy purchase? Fundamental research beginning in the 1970s led to the development of epilepsy animal models that enabled the screening of drugs for anticonvulsant properties. The NIH then funded and provided oversight of a program of accelerated screening of