Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures.
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 > or =25% reduction: 68.6% vs 51.6% (P = .005); > or =50%: 37.3% vs 28.8% (P = .093); and > or =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.
Silberstein
Stephen
S
Thomas Jefferson University, Department of Neurology, Philadelphia, PA 19107, USA.
Lipton
Richard
R
Dodick
David
D
Freitag
Fred
F
Mathew
Ninan
N
Brandes
Jan
J
Bigal
Marcelo
M
Ascher
Steven
S
Morein
Jacqueline
J
Wright
Pamela
P
Greenberg
Steven
S
Hulihan
Joseph
J
D000700:Analgesics / Q000627:therapeutic use; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects; D004185:Disability Evaluation; D004311:Double-Blind Method; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods; D020795:Photophobia / Q000188:drug therapy / Q000209:etiology; D010919:Placebos; D011788:Quality of Life / Q000523:psychology; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome; D014839:Vomiting / Q000188:drug therapy / Q000209:etiology
D000700:Analgesics; D000927:Anticonvulsants; D010919:Placebos; D000077236:Topiramate; D005632:Fructose