Topiramate has been shown to be effective as a preventive treatment for migraine in three large placebo-controlled, dose-ranging trials. Because the protocols were similar in design using the same primary and secondary endpoints, data from these studies were pooled to evaluate the consistency of efficacy, efficacy by gender and tolerability of topiramate 100 mg/day (n = 386) versus placebo (n = 372). Topiramate was superior to placebo as measured by the reduction in mean monthly migraine frequency, monthly migraine days and monthly migraine duration. The responder rates, defined as at least 50% reduction for the respective parameters, were significantly in favour of topiramate (p < 0.001), for example 46.3% of patients on topiramate achieved at least 50% reduction in monthly migraine period frequency compared with 22.8% on placebo (p < 0.001). Use of medication to treat the acute migraine attack was significantly reduced by topiramate compared with placebo (p < 0.001). The therapeutic effect was consistent throughout the different studies and independent of gender. The most common adverse effect was paraesthesia, mostly of mild-to-moderate severity. The findings confirm that, at a dose of 100 mg/day, topiramate is an effective and well-tolerated drug for migraine prevention.

Patients receiving topiramate experienced a sustained reduction in migraine frequency for up to 14 months. The effectiveness and safety of topiramate was consistent with that observed during 2 26-week pivotal trials.

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

In 20 patients with pure menstrual migraine either Estraderm TTS 50 patches (E) or placebo (P) patches were applied during three successive menstrual cycles, randomly allocated to the treatment sequences E-P-E or P-E-P. Clinical neurophysiological tests, contingent negative variation (CNV) and exteroceptive temporalis muscle suppression test (ETST) were performed before treatment. The predictive value of these tests regarding the efficacy of Estraderm TTS was studied. Neither the number, duration and severity of the migraine attacks, nor the consumption of analgesics and ergotamine differed significantly during Estraderm TTS and placebo treatment. The ETST was consistent with migraine in 35% (95% confidence interval 15.4 to 59.2) of the patients. The CNV in 55% (31.5 to 76.9), and both tests in 25% (8.7 to 49.1%). Regarding the prediction of the Estraderm TTS effect on the migraine attacks, the specificity of the ETST, CNV and the combination of ETST with CNV, calculated for the first two cycles, was respectively 81.8% (48.2 to 97.7), 45.5% (16.8 to 76.6) and 80% (28.4 to 99.5). For the last two cycles these values were respectively 75% (42.8 to 94.5), 50.0% (21.1 to 87.9) and 71.4% (29.0 to 96.3). The sensitivity of the tests was respectively 62.5% (24.5 to 91.5), 62.5% (24.5 to 91.5) and 66.7% (22.3 to 95.7) in the first 2 cycles. In the last 2 cycles 50.0% (15.1 to 84.3), 62.5% (24.5 to 91.5) and 60% (14.7 to 94.7). This study did not demonstrate an effectiveness of Estraderm TTS in perimenstrual migraine, except for the subgroup of perimenstrual migraine patients in whom the ETST test results were consistent with migraine.

Preventive treatment with topiramate in patients with episodic migraine may reduce the risk of developing chronic forms of headache.