Abstract and Introduction
Abstract
Objective.—To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial.
Background.—We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated.
Methods.—Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change.
Results.—The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for ≥25% reduction: 68.6% vs 51.6% (P = .005); ≥50%: 37.3% vs 28.8% (P = .093); and ≥75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062).
Conclusions.—In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.
Introduction
Migraine is one of the leading causes of disability, affecting approximately 11.7% of the adult population in the USA. The total direct and indirect costs associated with migraine approach that associated with all cerebrovascular disease.
Some migraineurs are at risk for progression of their condition, marked by a gradual increase in the frequency of headache days over time. In the revised International Classification of Headache Disorders (ICHD) chronic migraine is defined as headache (tension-type and/or migraine) occurring on at least 15 days per month for at least 3 months in a patient who has had at least 5 attacks fulfilling ICHD criteria for 1.1 migraines without aura; on at least 8 days per month for at least 3 months, the headaches fulfilled criteria for pain and associated symptoms of migraine without aura or were treated and relieved by triptan(s) or ergot before the expected development of migraine-associated symptoms. Chronic migraine is associated with greater costs and disability than episodic migraine.
Preventive migraine treatments are widely used in clinical practice for the management of chronic migraine, although evidence from clinical trials supporting the efficacy of these treatments for this use is generally lacking.
Topiramate is approved for migraine prevention in adults. Two large-scale, randomized, double-blind, placebo-controlled clinical trials have shown that treatment with topiramate 100 mg per day is an effective, safe, and generally well-tolerated preventive treatment for episodic migraine. In addition, results from a large, multicenter, randomized, double-blind, placebo-controlled, parallel group study demonstrated that treatment of subjects with chronic migraine with topiramate 100 mg per day resulted in statistically significant reductions in mean monthly migraine/migrainous headache days (primary efficacy outcome) and migraine days per month (a second prespecified key efficacy outcome), and the drug was found to be safe and generally well-tolerated. A second randomized trial also showed topiramate to be effective in the treatment of chronic migraine.
We present herein results for prespecified secondary efficacy analyses including migraine-specific symptoms and health-related quality of life [HRQoL]) from the larger of these studies.