Looking to the future: Research designs for study of headache disease progression

Evidence from clinical observation and population studies suggests that migraine sometimes transforms into chronic migraine. Risk factors for progression include headache frequency, obesity, snoring, stressful life events, and head injury. Other candidate risk factors include depression, anxiety, and lifestyle factors. Progression in a subgroup only raises the possibility that risk factor management or other forms of treatment may prevent migraine progression. Herein, we consider the design of clinical trials for interventions which could prevent the transformation of migraine to chronic migraine. We recommend enrolling individuals at high risk for progression based on baseline high headache frequency, delivering intervention in the context of a double-blind randomized trial and assessing either the onset of chronic migraine or major change in headache frequency as outcomes.