Chronic daily headache (CDH) comprises a group of heterogeneous disorders characterized by the occurrence of headaches on at least 15 days per month.1–3 In subspecialty care, most subjects with CDH have a form of the disorder linked to migraine.1,4,5 Terminology and diagnostic criteria for these disorders continue to evolve. Transformed migraine has been proposed to be a subtype of CDH; the term is widely used to describe patients who have a history of episodic migraine in which the frequency of headache episodes increases until the patients experience daily or near-daily migrainous and nonmigrainous headaches.4–6
In the International Classification of Headache Disorders-2 (ICHD-2), chronic migraine was defined by the presence of migraine without aura 15 or more days per month.2 More recently, a revision was proposed requiring 15 or more headache days per month with migraine or response to triptans or ergots on at least 8 days.3 For the purposes of this study, chronic migraine was defined as the presence of at least 15 headache days per 28 days, of which at least half were migraine (International Headache Society; IHS 1.1 or 1.2) or migrainous headache. The criteria for this protocol were determined at the same time as the ICHD-2 criteria for chronic migraine were being discussed. Although migraine terminology has continued to evolve, evidence suggests a very high degree of overlap using various definitions for chronic migraine based on different criteria.7 In addition, although the term probable migraine was discussed as being more descriptive of headaches that did not meet all criteria for migraine headache, the term migrainous headache was still widely used at the time.
CDH and its subtypes are an important public health priority associated with a high degree of disability that exceeds episodic migraine;8 CDH has been linked to overuse of acute headache pain medicines.9,10 Also, patients with CDH often have been considered to be refractory to preventive medications, especially when acute “symptomatic” medications for acute headache are being overused.11 Preventive treatments for patients with frequent or severe episodic migraine are widely used in clinical practice for preventive treatment of chronic migraine, typically in the absence of evidence from controlled trials that would support such a practice.12,13 Accordingly, chronic migraine is a disease state characterized by severe disability, important unmet treatment needs, and lack of rigorous evidence to support therapies currently employed.
Topiramate is approved for use in adults for migraine prevention. In several randomized, double-blind, placebo-controlled, dose-ranging trials involving adult patients with episodic migraine, topiramate treatment resulted in significant benefit compared with placebo, with efficacy observed within the first month of treatment.14–16 The results from these trials confirmed topiramate 100 mg/day to be an effective, safe, and generally well-tolerated preventive treatment for migraine.14–17
In 2 separate small, single-center, randomized, double-blind, placebo-controlled, or active-comparator-controlled pilot trials, topiramate significantly lowered the mean monthly headache frequency in patients with chronic migraine.18,19 To confirm these data, we designed the current large, multicenter study to evaluate the efficacy and safety of topiramate 100 mg/day for the treatment of chronic migraine.