Journal of Neurology

, Volume 251, Issue 8, pp 943– 950 | Cite as

Topiramate in migraine prophylaxis

Results from a placebo–controlled trial with propranolol as an active control
  • Hans-Christoph DienerEmail author
  • P. Tfelt-Hansen
  • C. Dahlöf
  • M. J. A. Láinez
  • G. Sandrini
  • Sh.-J. Wang
  • W. Neto
  • U. Vijapurkar
  • A. Doyle
  • D. Jacobs
  • on behalf of the MIGR-003 Study Group


Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo–controlled, dose–ranging trials. We conducted a randomised, doubleblind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised 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 subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine 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 generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.

Key words

placebo–controlled  migraine topiramate prophylaxis propranolol 


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  1. 1.
    Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D (2004) Topiramate for migraine prevention: a randomized controlled trial. JAMA 291:965–973CrossRefPubMedGoogle Scholar
  2. 2.
    Dahlof C, Linde M (2001) One-year prevalence of migraine in Sweden: a population-based study in adults. Cephalalgia 21:664–671CrossRefPubMedGoogle Scholar
  3. 3.
    Diener H-C, Goadsby PJ (2003) Migraine. In: Brandt T, Caplan L, Dichgans J, Diener H-C, Kennard C (eds) Course and treatment of neurological disorders. 2nd edition. Academic Press, San Diego, pp 1–16Google Scholar
  4. 4.
    Edwards KR, Glantz MJ, Norton JA, Cross N (2000) Prophylactic treatment of episodic migraine with topiramate: a double-blind, placebo-controlled trial in 30 patients. Cephalalgia 20:316Google Scholar
  5. 5.
    Freitag FG, Collins SD, Carlson HA, Goldstein J, Saper J, Silberstein S, Mathew N, Winner PK, Deaton R, Sommerville K (2002) A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology 58:1652–1659 PubMedGoogle Scholar
  6. 6.
    Goadsby PJ, Lipton RB, Ferrari MD (2002) Migraine–current understanding and treatment. N Engl J Med 346:257–270CrossRefPubMedGoogle Scholar
  7. 7.
    Headache Classification Committee of the International Headache Society (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 8(suppl 7):1–96CrossRefGoogle Scholar
  8. 8.
    Katsarava Z, Fritsche G, Muessig M, Diener HC, Limmroth V (2001) Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 57:1694–1698PubMedGoogle Scholar
  9. 9.
    Klapper J (1997) Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia 17:103–108CrossRefPubMedGoogle Scholar
  10. 10.
    Mathew NT, Saper JR, Silberstein SD, Rankin L, Markley HG, Solomon S, Rapoport AM, Silber CJ, Deaton RL (1995) Migraine prophylaxis with divalproex. Arch Neurol 52:281–286PubMedGoogle Scholar
  11. 11.
    Rasmussen BK, Olesen J (1992) Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia 12:221–228 CrossRefPubMedGoogle Scholar
  12. 12.
    Silberstein SD (2000) Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 55:754–762PubMedGoogle Scholar
  13. 13.
    Silberstein SD, Neto W, Schmitt J, Jacobs D (2004) Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 61:490–495CrossRefPubMedGoogle Scholar
  14. 14.
    Storey JR, Calder CS, Hart DE, Potter DL (2001) Topiramate in migraine prevention: a double-blind, placebo-controlled study. Headache 41:968–975CrossRefPubMedGoogle Scholar
  15. 15.
    Tukey JW, Ciminera JL, Heyse JF (1985) Testing the statistical certainty of a response to increasing doses of a drug. Biometrics 41:295–301PubMedGoogle Scholar
  16. 16.
    van der Kuy P-HM, Lohman JJHM (2002) A quantification of the placebo response in migraine prophylaxis. Cephalalgia 22:265–270CrossRefPubMedGoogle Scholar

Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • Hans-Christoph Diener
    • 1
    Email author
  • P. Tfelt-Hansen
    • 2
  • C. Dahlöf
    • 3
  • M. J. A. Láinez
    • 4
  • G. Sandrini
    • 5
  • Sh.-J. Wang
    • 6
  • W. Neto
    • 7
  • U. Vijapurkar
    • 7
  • A. Doyle
    • 7
  • D. Jacobs
    • 7
  • on behalf of the MIGR-003 Study Group
  1. 1.Department of NeurologyUniversity EssenEssenGermany
  2. 2.Department of NeurologyUniversity of Copenhagen Glostrup HospitalGlostrupDenmark
  3. 3.Gothenburg Migraine ClinicGothenburgSweden
  4. 4.Department of NeurologyHospital Clinico Universitario University of ValenciaValenciaSpain
  5. 5.Headache Centre IRCC C. Mondino FoundationUniversity of PaviaPaviaItaly
  6. 6.Neurological Institute TaipeiVeterans General Hospital and National Yang-Ming University School of MedicineTaipeiTaiwan
  7. 7.Johnson & JohnsonPharmaceutical Research and DevelopmentLLC RaritanNJ USA

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