Rofecoxib in the Acute Treatment of Migraine: A Randomized Controlled Clinical Trial


  • Joel Saper MD,

  • Carl Dahlof MD,

  • Yuen So MD,

  • Peer Tfelt-Hansen MD,

  • William Malbecq PhD,

  • Thomas Loeys PhD,

  • Eleathea Barraclough BA,

  • Meghan Klipfel MS,

  • Christopher Lines PhD,

  • Hester Visser MD,

  • Scott Reines MD,

  • Eric Yuen MD,

  • on behalf of the Rofecoxib Protocol 162 Study Group

  • Michigan Head Pain & Neurological Institute, 3120 Professional Drive, Ann Arbor, MI (Dr. Saper); Gothenburg Migraine Clinic, Lakarhuset, Sodra vagen 27, S-41135 Gothenburg, Sweden (Dr. Dahlof); Department of Neurology, Stanford University Medical Center, Stanford, CA (Dr. So); Department of Neurology, Glostrup Hospital, Glostrup, Denmark (Dr. Tfelt-Hansen); Merck, Sharp & Dohme (Europe), Brussels, Belgium (Drs. Malbecq and Loeys); and Merck Research Laboratories, West Point, PA (Ms. Barraclough and Ms. Klipfel, and Drs. Lines, Visser, Reines, and Yuen).

Address all correspondence to Christopher Lines, Merck & Co., Inc., PO Box 4, West Point, PA 19486.


Objective.—To investigate the efficacy, tolerability, and safety of rofecoxib and ibuprofen for acute migraine treatment.

Background.—Rofecoxib was effective and well tolerated in a previous study of treatment of a single migraine attack. We sought to replicate these findings for a single attack and also study the clinical profile of rofecoxib in the acute treatment of multiple migraine attacks. Ibuprofen was included as a reference nonselective NSAID.

Methods.—Adult migraineurs (n = 783) treated one migraine attack with either rofecoxib (25 or 50 mg), ibuprofen 400 mg, or placebo in a randomized, double-blind study. Patients could elect to enroll in a 3-month double-blind extension phase.

Results.—In the single-attack phase, headache relief at 2 hours postdose was reported by 59.4%, 62.2%, and 57.7% of patients who took rofecoxib 25 mg, rofecoxib 50 mg, and ibuprofen 400 mg, respectively, versus 30.5% for placebo (all P < .001 vs placebo). The active drugs were statistically superior to placebo on a variety of additional measures. In the extension phase, the mean percentage of patients' attacks with headache relief at 2 hours postdose was 61.8% for rofecoxib 25 mg, 65.4% for rofecoxib 50 mg, and 59.3% for ibuprofen 400 mg. The mean percentage of patients' attacks with 24-hour sustained headache relief was greater for rofecoxib 50 mg (52.0%) than for rofecoxib 25 mg (47.8%, P < .050) or ibuprofen (39.0%, P < .010). In the single-attack phase, the adverse event rate was higher for rofecoxib 50 mg (37.8%) than placebo (27.8%, P < .050); rates were similar to placebo for rofecoxib 25 mg (32.0%, n.s.) and ibuprofen 400 mg (28.1%, n.s.). In the extension phase, treatment groups had similar adverse event rates.

Conclusions.—Rofecoxib 25 and 50 mg and ibuprofen 400 mg were effective and generally well tolerated in the acute treatment of migraine.