Efficacy of Zolmitriptan at Early Time-Points for the Acute Treatment of Migraine and Treatment of Recurrence
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Objective and Study Design: This double-blind, placebo-controlled trial assessed the efficacy of zolmitriptan versus placebo at early time-points post-dose as an acute treatment for migraine and treatment of headache recurrence.
Patients and Methods: Patients (18 to 65 years) with a ≥1-year history of migraine, age of onset <50 years and an average of 2 to 6 migraine headaches per month were recruited by 45 North American research clinics. 1017 patients were randomised to receive treatment for each of 3 migraine headaches of moderate or severe baseline intensity (labelled A, B and C, and given in a randomised order). Within each headache, patients were randomly allocated to different treatment regimens. Each patient treated each of the 3 headaches (A, B and C) with up to 3 doses, i.e. an initial dose (headache A, zolmitriptan 2.5mg or placebo; headache B, zolmitriptan 5mg or placebo; headache C, zolmitriptan 2.5mg), recurrence prevention 8 hours after initial dose [headache A and B, placebo (to maintain blind); headache C, zolmitriptan 2.5mg or placebo] and a recurrence treatment dose, if required (headache A and B, zolmitriptan 2.5mg or placebo; headache C, zolmitriptan 2.5mg). The 2 primary end-points were headache response rates 45 minutes after the initial dose of zolmitriptan 2.5 or 5mg or placebo, and headache response rates 2 hours after zolmitriptan 2.5mg or placebo for the treatment of recurrent headache, in patients responding at 4 hours to the initial dose.
Results: A total of 734 patients treated all 3 headaches. Headache response following an initial dose of zolmitriptan 2.5 and 5mg was significantly greater than placebo by 45 minutes (p < 0.001, p < 0.01, respectively) and was maintained at 1, 2 and 4 hours. Headache response following zolmitriptan treatment for recurrence was higher than that for placebo, but the difference did not reach statistical significance. A dose taken 8 hours after the initial dose did not appear to provide any benefit in preventing recurrent headache.
Conclusions: Zolmitriptan 2.5 and 5mg provides a rapid onset of action with significant relief of migraine headache by 45 minutes post-dose compared with placebo.
KeywordsMigraine Initial Dose Sumatriptan Migraine Attack Migraine Headache
This study was sponsored by Zeneca Pharmaceuticals.
We would like to thank the investigators who took part in this study: M. Alexander (Niagara Falls, Ontario, Canada); S.K. Aurora (Detroit, Michigan, USA); R.K. Bath (Cincinnati, Ohio, USA); W.J. Becker (Calgary, Alberta, Canada); S.D. Bleser (Bellbrook, Ohio, USA); D.W. Brown (Austin, Texas, USA); J.R. Caldwell (Daytona Beach, Florida, USA); J.R. Couch (Oklahoma City, Oklahoma, USA); J.D. Dexter (Columbia, Missouri, USA); S. Diamond (Chicago, Illinois, USA); A.P. Dietrich (Woodstock, Vermont, USA); V.A. Elinoff (Endwell, New York, USA); A.H. Elkind (Mount Vernon, New York, USA); J.A. Gezon (Salt Lake City, Utah, USA); R.A.M. Giammarco (Hamilton, Ontario, Canada); J. Goldstein (San Francisco, California, USA); R.K. Hippert (Fleetwood, Pennsylvania, USA); J.A. Holmes (Mission, Kansas, USA); J.T. Hormes (Marietta, Georgia, USA); C.M. Jackson (San Diego, California, USA); P.D. Kanof (Tucson, Arizona, USA); N.M. Kassman (Statesville, North Carolina, USA); A.E. Koff (Philadelphia, Pennsylvania, USA); S.J. Kolesk (Mt Laurel, New Jersey, USA); J.P. Levine (East Brunswick, New Jersey, USA); F.P. Maggiacomo (Cranston, Rhode Island, USA); N.T. Mathew (Houston, Texas, USA); A. Mauskop (Brooklyn, New York, USA); J.M. McCarty (Fresno, California, USA); R.B. Nett (San Antonio, Texas, USA); T.M. Nolen (Columbiana, Alabama, USA); P. Patel (Mississauga, Ontario, Canada); R.C. Reed (Cleveland, Ohio, USA); M.D. Reynolds (Dallas, Texas, USA); M.A. Rosemore (Hueytown, Alabama, USA); R.E. Ryan (Chesterfield, Missouri, USA); CH Sadowsky (West Palm Beach, Florida, USA); A. Shuaib (Saskatoon, Saskatchewan, Canada); C.F. Springgate (New Britain, Connecticut, USA); M.S. Touger (Birmingham, Alabama, USA); M.J. Weinstein (East Brunswick, New Jersey, USA); K.M.A. Welch (Detroit, Michigan, USA); T. Williams (Peoria, Arizona, USA); R.M. Willis (Harrogate, Tennessee, USA); M.C.B. Wilson (Tampa, Florida, USA); G.W. Wolfley (Scottsdale, Arizona, USA); and S. Zeig (Ft Lauderdale, Florida, USA).
- 1.Stewart WF, Lipton RB, Celentano DD, et al. Prevalence ofmigraine headache in the United States. Relation to age, income, race and other sociodemographic factors. JAMA 1992; 267: 64–9Google Scholar
- 3.Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia 1988; 8 Suppl. 7: 1–96Google Scholar
- 8.Rapoport AM, Ramadan NM, Adelman JU, et al. Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. Neurology 1997; 49: 1210–8Google Scholar
- 14.Lines C, Visser WH, Vandormael K, et al. Rizatriptan 5mg versus sumatriptan 50mg in the acute treatment of migraine [abstract and poster]. 39th Annual Scientific Meeting of the American Association for the Study of Headache: 1997 Jun 19–22; New York. Headache 1997; 37: 319–20Google Scholar
- 20.Bomhof M, Paz J, Legg N, et al. Comparison of rizatriptan 10mg vs. naratriptan 2.5mg in migraine. Eur Neurol 1999; 42: 173–9Google Scholar
- 22.Teall J, Tuchman M, Cutler N, et al. Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Headache 1998; 38: 281–7Google Scholar
- 23.MacGregor A. Management of migraine in general practice. Prescriber 1998; 9: 49,53-54,58Google Scholar
- 24.Block GA, Kramer M-S, Matzura-Wolfe D, et al. Long-term exposure to rizatriptan 5mg and 10mg oral tablets [abstract and poster]. 39th Annual Scientific Meeting of the American Association for the Study of Headache: 1997 Jun 19–22; New York. Headache 1997; 37: 302Google Scholar
- 28.Edmeads J, Millson DS. Tolerability profile of zolmitriptan (Zomig™; 311C90), a novel dual central and peripheral 5HT1B/1D agonist. Cephalalgia 1997; 17 Suppl. 18: 41–52Google Scholar