Treatment of menstruation-associated migraine with the nonprescription combination of acetaminophen, aspirin, and caffeine: results from three randomized, placebo-controlled studies.

This retrospective study sought to examine the benefits of the nonprescription combination of acetaminophen, aspirin, and caffeine (AAC; Excedrin Migraine, Bristol-Myers Squibb Company, New York, New York) for the treatment of menstruation-associated migraine compared with migraine not associated with menses. Data were derived from 3 double-masked, randomized, placebo-controlled, single-dose trials enrolling subjects who met the International Headache Society's diagnostic criteria for migraine with or without aura. Subjects with incapacitating disability (attacks requiring bed rest >50% of the time) and those who usually experienced vomiting > or =20% of the time were excluded. Retrospective analysis of the 1220 subjects included in the efficacy-evaluable data set indicated that 185 women treated menstruation-associated migraine, 781 women treated migraine not associated with menses, and 1 woman provided no information regarding menstrual status. At baseline and at 0.5, 1, 2, 3, 4, and 6 hours postdose, subjects assessed the intensity of headache pain, functional disability, nausea, photophobia, and phonophobia. Pain intensity, nausea, photophobia, and phonophobia were rated on a 4-point scale ranging from 0 = none to 3 = severe; functional disability was rated on a 5-point scale ranging from 0 = none to 4 = incapacitating. For both menstruation-associated migraine and migraine not associated with menses, the proportion of subjects with pain intensity reduced to mild or none (responders) was significantly greater with AAC than with placebo at all postdose time points from 0.5 through 6 hours (P< or =0.05), with no statistically significant difference in treatment effect between menstruation-associated migraine and migraine not associated with menses at any postdose time point. Migraine characteristics such as photophobia, phonophobia, and functional disability were significantly improved in AAC-treated subjects at all time points from 1 through 6 hours (P< or =0.01) in both the menstruating and nonmenstruating groups. Significant relief from nausea was experienced in both menstruation-associated migraine and migraine not associated with menses, but relief appeared earlier in the AAC nonmenstruating subjects (2 hours postdose, P< or =0.01) than in the menstruating subjects (6 hours postdose, P< or =0.05). Beginning at 3 hours postdose, significantly fewer subjects treated with AAC required rescue medication (P< or =0.05) for menstruation-associated migraine (AAC 6%, placebo 15%) and migraine not associated with menses (AAC 7%, placebo 14%). The most commonly used rescue medications in both the menstruating and nonmenstruating groups were nonsteroidal anti-inflammatory drugs, prescription combination analgesics/narcotics, and prescription migraine preparations. AAC was well tolerated in both menstruation-associated migraine and migraine not associated with menses; in general, adverse experiences were similar in both groups. The proportion of subjects who had 1 or more adverse experiences was significantly higher among those receiving AAC than among those receiving placebo (menstruation-associated migraine: AAC 26.4%, placebo 12.6%, P = 0.025; nonmenstruation-associated migraine: AAC 18.6%, placebo 11.4%, P = 0.005). Adverse experiences were similar in type and severity to those previously associated with single doses of acetaminophen, aspirin, or caffeine. Thus the nonprescription combination of AAC was highly effective in treating the pain, disability, and associated symptoms of both menstruation-associated migraine and migraine not associated with menses.