Topiramate for the Prophylaxis of Episodic Migraine in Adults

Summary

A Cochrane review [Abstract] 1 included 17 studies with a total of 3543 patients with episodic migraine. Topiramate was compared with placebo (10 trials), to another active intervention (7 trials) and different doses were directly compared in 3 trials. The doses of topiramate investigated ranged from 50 to 200 mg/day. The duration of the treatment phase of the included trials varied from 4 to 52 weeks, with a mean of 19 weeks.

• Topiramate vs. placebo: headache frequency reduced by about 1.2 attacks per 28 days (MD -1.20; 95% CI -1.59 to -0.80; 9 trials, n=1737). It approximately doubled the proportion of responders relative to placebo (RR 2.02; 95% CI 1.57 to 2.60; NNT 4; 95% CI 3 to 6; 9 trials, n=1190). Separate analysis of different topiramate doses produced similar MDs vs. placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; 3 studies; n=520), 100 mg (-1.15; 95% CI -1.58 to -0.71; 6 studies; n=1620) and 200 mg (-0.94; 95% CI -1.53 to -0.36; 5 studies; n=804). All 3 doses significantly increased the proportion of responders relative to placebo; ORs were as follows: for 50 mg, 2.35 (95% CI 1.60 to 3.44; 3 studies, n=519); for 100 mg, 3.49 (95% CI 2.23 to 5.45; 5 studies; n=852); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; 6 studies; n=1025). All 3 doses also significantly improved 3 or more domains of quality of life as compared to placebo. Meta-analysis of the 3 studies that included more than one dose of topiramate suggests that 200 mg is no more effective than 100 mg. Seven adverse events (AEs) were reported by at least 3 studies. These were usually mild and of a non-serious nature. Except for taste disturbance and weight loss, there were no significant differences in the frequency of AEs in general, or of the 7 specific AEs, between placebo and topiramate 50 mg. AEs in general and all of the specific AEs except nausea were significantly more common on topiramate 100 mg than on placebo, with NNHs varying from 3 to 25, and the RDs vs. placebo were even higher for topiramate 200 mg, with NNHs varying from 2 to 17.
• Topiramate vs. active comparators (7 trials): when headache frequency and/or responder rate were evaluated, there was no significant differences between topiramate and amitriptyline (1 study, n=330); flunarizine (1 study, n=83); propranolol (2 studies, n=342); relaxation (1 study, n=61); but a slight significant advantage of topiramate over valproate was seen (MD -1.20; 95% CI -2.16 to -0.24; 2 studies, n=120). Relaxation improved migraine-specific quality of life significantly more than topiramate.