Topiramate versus amitriptyline in migraine prevention: A 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs

Abstract Objective: The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache. Methods: This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment. Results: The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains o