J Neurol (2004) 251 : 943–950 DOI 10.1007/s00415-004-0464-6 ORIGINAL COMMUNICATION Hans-Christoph Diener Peer Tfelt-Hansen Carl Dahlöf Miguel J. A. Láinez Giorgio Sandrini Shuu-Jiun Wang Walter Neto Ujjwalla Vijapurkar Aiden Doyle David Jacobs on behalf of the MIGR-003 Study Group Topiramate in migraine prophylaxis Results from a placebo-controlled trial with propranolol as an active control Introduction The one-year prevalence of migraine after puberty is 12 % for women and 6 % for men [11].About 25 % of mi- graine patients have a high frequency of migraine at- tacks, with up to 6 per month, leading to considerable disability and consequences for professional life (e. g., work loss) or social function (e. g., care of family) [2]. A high frequency of migraine attacks can lead to frequent JON 1464 Received: 2 January 2004 Received in revised form: 27 February 2004 Accepted: 8 March 2004 Prof. Dr. Hans-Christoph Diener () Department of Neurology University Essen Hufelandstr 55 45122 Essen, Germany Tel.: +49-201/723-2460 Fax: +49-201/723-5901 E-Mail: h.diener@uni-essen.de P. Tfelt-Hansen, MD, PhD Department of Neurology University of Copenhagen Glostrup Hospital Glostrup, Denmark C. Dahlöf, MD, PhD Gothenburg Migraine Clinic Gothenburg, Sweden M. J. A. Láinez, MD, PhD Department of Neurology Hospital Clinico Universitario University of Valencia Valencia, Spain G. Sandrini, MD Headache Centre IRCC C. Mondino Foundation University of Pavia Pavia, Italy Sh.-J. Wang, MD Neurological Institute Taipei Veterans General Hospital and National Yang-Ming University School of Medicine Taipei, Taiwan W. Neto, MD · U. Vijapurkar, PhD · A. Doyle, MD · D. Jacobs, MD Johnson & Johnson Pharmaceutical Research and Development LLC Raritan, NJ USA ■ Abstract Topiramate (TPM) has shown efficacy in migraine prophy- laxis in two large placebo-con- trolled, dose-ranging trials. We conducted a randomised, double- blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for mi- graine prophylaxis, with propra- nolol (PROP) as an active control. Subjects with episodic migraine with and without aura were ran- domised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five sub- jects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine fre- quency, overall 50% responder rate, reduction in monthly mi- graine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was gen- erally comparable to PROP. No un- usual or unexpected safety risks emerged. These findings demon- strate that TPM 100 mg/d is effec- tive in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d ex- hibited similar efficacy profiles. ■ Key words placebo-controlled · migraine · topiramate · prophylaxis · propranolol