Topiramate for migraine prevention
Clinical bottom line
Topiramate at doses up to 100 mg daily significantly reduces the frequency of chronic migraine. The proportion of patients with at least 50% reduction in headache frequency is 46%, and 26% have at least 75% reduction in frequency. Compared with placebo, NNTs are 4.1 for a 50% reduction, and 6.2 for a 75% reduction.
Topiramate is an anticonvulsant, and this class of compounds has previously been shown to reduce the frequency of chronic migraine headaches, though the randomised trial evidence base is limited.
Randomised trials comparing topiramate with placebo or active comparator were sought in PubMed, to the end of 2005. Any trial was accepted that was randomised and double blind, used any dose regimen of topiramate, in patients with chronic migraine headache (at least two episodes a month), used standard diagnostic classification, and was at least of four weeks duration. The main outcomes sought were the number or proportion of patients with migraine frequency reduced by at least 50%, and adverse events.
Two randomised trials, and one pooled analysis of other three randomised trials, were found (details in Table 1). Two of the trials in the pooled analysis were also published individually, but these were not included.
Table 1: Details of randomised trials with topiramate for migraine prevention
|Reference||Study design||Patients||Efficacy||Adverse events|
|Bussone et al. Int J Clin Pract 2005 59: 961-968||Pooled analysis of 3 randomised, double blind, trials comparing topiramate
After 14 days without drugs, 28 days baseline phase, followed by 8 weeks titration and 18 weeks of maintenance
Topiramate 50-200 mg/day (n=386)
|Migraine with or without aura , 12-65 years, established history of
migraine using HIS criteria for 6-12 months. No more than 15 headache
days per 28 days
Mean migraine days 6.4
|Topiramate significantly reduce migraine days and duration by about
At least 50% reduction 177/382 with topiramate, 85/372 with placebo
At least 75% reduction 96/382, 37/372
Days with migraine medication decreased to 13 from 20 days per month
|Adverse event withdrawal was higher with topiramate (24%) than placebo
(11%). Lack of efficacy withdrawal higher for placebo (15%) than topiramate
Main adverse events were parasthesia, fatigue, anorexia, and mood problems. Mean weight loss 2.5 kg on topiramte, no change with placebo
|Silvestrini et al. Cephalalgia 2003 23: 820-824||Randomised, double blind trials of topiramate and placebo, consisting
of 8 week baseline pahase, 1 week titration phase, and 8 week maintenance
Topiramate 50 mg (n=14)
|Patients with chronic migraine with medication overuse, with at least
10 year history of chronic migraine, and who had failed to respond to
at least four preventative medications at adequate dose and for adequate
Mean headache days 20/28 days, analgesic intake 26/28 days
|Topiramate significantly reduced headache froquency from 21/28 days
at baseline to 8/28 days at end, with no change with placebo
At least 50% reduction 10/14 topiramate, 1/14 placebo
At least 75% reduction 6/14, 0/14
At least 90% reduction 4/14, 0/14
|Adverse event withdrawal with topiramate 1/14, 0/14 with placebo.
Adverse events 5/14 topiramate, 1/14 placebo
|Storey et al. Headache 2001 41: 968-975||Randomised, double blind comparison of topiramate and placebo consisting
of 4 week baseline phase, 8 week titration, and 8 weeks maintenance
Topiramate up to 100 mg daily (n=19)
|Patients with established migraine using HIS criteria, for more than one year, at frequency of 2 or more attacks per month. Age 18-65 years||Mean monthly migraine frequeny fell significantly more with topiramate
than placebo, from 5.1 to 3.3 days on average
At least 50% reduction 5/19 topiramate, 2/21 placebo
|Adverse event discontinuations 2/19 topiramate, 0/21 placebo
Total discontinuation 3/19, 2/21
Adverse events included parasthesia, weight loss, and altered taste. Weight loss with topiramate was about 2.5 kg
Overall, 192/415 (46%) patients on topiramate had at least 50% reduction in headache frequency, compared with 88/407 (22%) on placebo. The relative benefit was 2.1 (95% CI 1.7 to 2.6) and the number needed to treat for one additional patient to have reduced frequency was 4.1 (3.2 to 5.4).
Overall, 102/396 (26%) patients on topiramate had at least 75% reduction in headache frequency, compared with 37/386 (9.7%) on placebo. The relative benefit was 2.7 (95% CI 1.8 to 3.8) and the number needed to treat for one additional patient to have reduced frequency was 6.2 (4.7 to 9.1).
Adverse events included parasthesia, fatigue, mood swings and anorexia, with about one patient in five discontinuing because of adverse events on topiramate. On average, patients on topiramate lost about 2.5 kg over eight weeks.
These consistent results from clinical trials are similar to those found in clinical practice . In this study of 115 patients who had not responded to or tolerated beta-blockers, amitriptyline, flunarizine, or valproate, 65 (56%) had at least 50% reduction in frequency, and 34 (30%) at least 75% reduction. Adverse events were also similar, with 21% withdrawing because of adverse events (mostly cognitive difficulties), and with weight loss of 3-13 kg in 16 (14%), 10 of whom were initially overweight.
- J Pascuel et al. Topiramate for patients with refractory migraine: an observational, multicentre study in Spain. Neurologia 2003 18: 364-367.