Topiramate in Patients With Episodic Migraine: Reducing the Risk for Chronic Forms of Headache


  • Volker Limmroth MD,

  • David Biondi DO,

  • Joop Pfeil MSc,

  • Susanne Schwalen MD

  • From the Department of Neurology, Cologne City Hospitals, Cologne, Germany (Dr. Limmroth); Department of Neurology, Massachusetts General Hospital, Boston, MA, USA (Dr. Biondi); Estimate Medical Statistics, BV Doesburg, The Netherlands (Mr. Pfeil); and Janssen-Cilag EMEA, Belgium (Dr. Schwalen).

Address all correspondence to Dr. Volker Limmroth, Cologne City Hospitals—Neurology, Ostmerheimerstr. 200, Cologne 51109, Germany.


Objective.—The aim was to evaluate whether preventive treatment with topiramate in patients with episodic migraine reduces the risk of developing chronic forms of headache.

Background.—Chronic forms of headache, including chronic migraine or medication overuse headache (MOH), are characterized by 15 or more headache days per month. Acute medication overuse has been shown to be a risk factor for developing chronic headache, but it is not known whether preventive treatment can reduce the risk of developing chronic forms of headache or the development of MOH.

Methods.—Pooled data from 3 trials in patients with episodic migraine randomized either to treatment with 100 mg topiramate per day (n = 384) or with placebo (n = 372) were analyzed with regard to the number of headache days during a prospective 4-week baseline period and the individual final 4 weeks of each patient's treatment during the planned 26-week double-blind treatment period.

Results.—The number of headache days per month in the topiramate versus the placebo-treated groups was 7.3 ± 3.0 versus 7.3 ± 3.1 during baseline and 4.1 ± 4.2 versus 5.6 ± 4.9 during the final 4 weeks, respectively (P < .001). At the end of the study, 8 versus 16 patients fulfilled International Headache Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a significantly lower number of patients receiving topiramate treatment reported an increase in headache days per month by the end of the study when compared to placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally, the number of days with usage of acute medication was significantly lower in the topiramate arm compared with placebo (3.3 ± 3.7 vs 4.3 ± 3.6, respectively; P < .001).

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