Two review authors independently selected studies and extracted data. For
headache frequency data, we calculated mean differences (MDs) between
topiramate and comparator (placebo, active control, or
topiramate in a different dose) for individual studies and pooled these across studies. For dichotomous data on responders (patients with ≥ 50% reduction in
headache frequency), we calculated odds ratios (
ORs) and, in select cases, risk ratios (RRs); we also calculated numbers needed to treat (NNTs). We calculated MDs for selected quality of life instruments. Finally, we summarised data on adverse events from placebo-controlled trials and calculated risk differences (RDs) and numbers needed to harm (NNHs).
MAIN RESULTS: Twenty papers describing 17 unique trials met the inclusion criteria. Analysis of data from nine trials (1737 participants) showed that
topiramate reduced
headache frequency by about 1.2 attacks per 28 days as compared to placebo (MD -1.20; 95% confidence interval (CI) -1.59 to -0.80). Data from nine trials (1190 participants) show that
topiramate 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). Separate analysis of different
topiramate doses produced similar MDs versus placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; three studies; 520 participants), 100 mg (-1.15; 95% CI -1.58 to -0.71; six studies; 1620 participants), and 200 mg (-0.94; 95% CI -1.53 to -0.36; five studies; 804 participants). All three 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; three studies; 519 participants); for 100 mg, 3.49 (95% CI 2.23 to 5.45; five studies; 852 participants); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; six studies; 1025 participants). All three doses also significantly improved three or more domains of quality of life as compared to placebo. Meta-analysis of the three studies that included more than one dose of
topiramate suggests that 200 mg is no more effective than 100 mg. With regard to mean
headache frequency and/or responder rate, seven trials using active comparators found (a) no significant difference between
topiramate and
amitriptyline (one study, 330 participants); (b) no significant difference between
topiramate and
flunarizine (one study, 83 participants); (c) no significant difference between
topiramate and
propranolol (two studies, 342 participants); (d) no significant difference between
topiramate and relaxation (one study, 61 participants); but (e) a slight significant advantage of
topiramate over
valproate (two studies, 120 participants). Relaxation improved
migraine-specific quality of life significantly more than
topiramate. In trials of
topiramate against placebo, seven adverse events (AEs) were reported by at least three 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 seven 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 versus placebo were even higher for
topiramate 200 mg, with NNHs varying from 2 to 17.
AUTHORS' CONCLUSIONS: Meta-analysis demonstrates that
topiramate in a 100 mg/day dosage is effective in reducing
headache frequency and reasonably well-tolerated in adult patients with episodic
migraine. This provides good evidence to support its use in routine clinical management. More studies designed specifically to compare the efficacy or safety of
topiramate versus other interventions with proven efficacy in the prophylaxis of
migraine are needed.