Julie McGinnis, MD

BACKGROUND: Acute migraine headache treatment may be approached in 3 ways. Stratified care implies treatment selection based on headache severity and associated disability. Step care either across a number of attacks or within an attack suggests choosing a common initial remedy that collectively optimizes efficacy, tolerability, and cost. Alternative regimens that may be higher in toxicity or cost are then progressively picked as necessary for treatment failure. Although commonly advocated for migraine management, these strategies have not yet been systematically compared to determine the best approach.

POPULATION STUDIED: Patients were eligible if they were aged 18 to 65 years and diagnosed with a migraine headache according to International Headache Society criteria. Subjects were recruited from 88 sites in 13 countries, but only those with a Migraine Disability Assessment Scale (MIDAS) of grade II, III, or IV were studied. Additional criteria included age at onset younger than 50 years, 1 to 8 attacks per month for the preceding 3 months, fewer than 10 nonmigraine headache days per month, and no change in preventive therapy during the trial. Participants were mostly women (83.2%), young (mean=37 years), and described their baseline disability as grade III or IV (mean=55%).

STUDY DESIGN AND VALIDITY: The study was conducted in an unblinded randomized parallel group design. During the 15-month period patients treated up to 6 moderate to severe migraines. The stratified group received care based on headache severity: Grade II was treated with aspirin 800 to 1000 mg plus metoclopramide 10 mg and grades III and IV with zolmitriptan 2.5 mg. The step care across attacks group all administered aspirin plus metoclopramide 10 mg as initial treatment. Therapy was escalated to zolmitriptan 2.5 mg in those that failed to respond in 2 of the first 3 attacks. Lack of response was defined as failure to reduce headache severity from moderate-severe to none-mild. All subjects in the step care within attacks group received the aspirin/metoclopramide combination as initial therapy but could add zolmitriptan if a response was not achieved within 2 hours. Efficacy and adverse effect data were self-reported on diary cards. Overall, the study was well conducted. Although the lack of treatment blinding is a potentially significant limitation, it may more closely approximate clinical practice. More importantly, the results may be different if other study drugs were chosen, and other agents are more commonly used in the United States. Finally, the results were not analyzed according to intention to treat and the dropout rate for the efficacy analysis was approximately 20%.

OUTCOMES MEASURED: The 2 primary outcomes were headache response at 2 hours and disability time per treated attack at 4 hours. Secondary end points included 1- and 4-hour responses, 2-hour pain-free response, and the occurrence of adverse events.

RESULTS: Headache response at 2 hours was significantly greater for stratified care than for either step care across attacks (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.31-2.12) or within attacks (OR=2.14; 95% CI, 1.66-2.77). These differences were mostly accounted for by the lack of response during the first 3 headaches (OR=2.91; 95% CI, 2.18-3.87) or within the first 2 hours of an attack, respectively. Disability time (from 0-4 hours) was also lower in the stratified care group than the step care across attacks group or the step care within attacks group. Again, there were no differences following treatment escalation in the step care groups. Adverse events were reported in approximately 14% of the attacks. They were more common in patients randomized to the stratified care group (19.5% vs 9.7% vs 13.1%). Those occurring less than 2% (asthenia, nausea, dizziness, paresthesias, and somnolence) were mild to moderate in severity and likely associated with zolmitriptan use. There was no difference in study withdrawal between treatment groups.

BACKGROUND: Acute migraine headache treatment may be approached in 3 ways. Stratified care implies treatment selection based on headache severity and associated disability. Step care either across a number of attacks or within an attack suggests choosing a common initial remedy that collectively optimizes efficacy, tolerability, and cost. Alternative regimens that may be higher in toxicity or cost are then progressively picked as necessary for treatment failure. Although commonly advocated for migraine management, these strategies have not yet been systematically compared to determine the best approach.

POPULATION STUDIED: Patients were eligible if they were aged 18 to 65 years and diagnosed with a migraine headache according to International Headache Society criteria. Subjects were recruited from 88 sites in 13 countries, but only those with a Migraine Disability Assessment Scale (MIDAS) of grade II, III, or IV were studied. Additional criteria included age at onset younger than 50 years, 1 to 8 attacks per month for the preceding 3 months, fewer than 10 nonmigraine headache days per month, and no change in preventive therapy during the trial. Participants were mostly women (83.2%), young (mean=37 years), and described their baseline disability as grade III or IV (mean=55%).

STUDY DESIGN AND VALIDITY: The study was conducted in an unblinded randomized parallel group design. During the 15-month period patients treated up to 6 moderate to severe migraines. The stratified group received care based on headache severity: Grade II was treated with aspirin 800 to 1000 mg plus metoclopramide 10 mg and grades III and IV with zolmitriptan 2.5 mg. The step care across attacks group all administered aspirin plus metoclopramide 10 mg as initial treatment. Therapy was escalated to zolmitriptan 2.5 mg in those that failed to respond in 2 of the first 3 attacks. Lack of response was defined as failure to reduce headache severity from moderate-severe to none-mild. All subjects in the step care within attacks group received the aspirin/metoclopramide combination as initial therapy but could add zolmitriptan if a response was not achieved within 2 hours. Efficacy and adverse effect data were self-reported on diary cards. Overall, the study was well conducted. Although the lack of treatment blinding is a potentially significant limitation, it may more closely approximate clinical practice. More importantly, the results may be different if other study drugs were chosen, and other agents are more commonly used in the United States. Finally, the results were not analyzed according to intention to treat and the dropout rate for the efficacy analysis was approximately 20%.

OUTCOMES MEASURED: The 2 primary outcomes were headache response at 2 hours and disability time per treated attack at 4 hours. Secondary end points included 1- and 4-hour responses, 2-hour pain-free response, and the occurrence of adverse events.

RESULTS: Headache response at 2 hours was significantly greater for stratified care than for either step care across attacks (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.31-2.12) or within attacks (OR=2.14; 95% CI, 1.66-2.77). These differences were mostly accounted for by the lack of response during the first 3 headaches (OR=2.91; 95% CI, 2.18-3.87) or within the first 2 hours of an attack, respectively. Disability time (from 0-4 hours) was also lower in the stratified care group than the step care across attacks group or the step care within attacks group. Again, there were no differences following treatment escalation in the step care groups. Adverse events were reported in approximately 14% of the attacks. They were more common in patients randomized to the stratified care group (19.5% vs 9.7% vs 13.1%). Those occurring less than 2% (asthenia, nausea, dizziness, paresthesias, and somnolence) were mild to moderate in severity and likely associated with zolmitriptan use. There was no difference in study withdrawal between treatment groups.

BACKGROUND: Acute migraine headache treatment may be approached in 3 ways. Stratified care implies treatment selection based on headache severity and associated disability. Step care either across a number of attacks or within an attack suggests choosing a common initial remedy that collectively optimizes efficacy, tolerability, and cost. Alternative regimens that may be higher in toxicity or cost are then progressively picked as necessary for treatment failure. Although commonly advocated for migraine management, these strategies have not yet been systematically compared to determine the best approach.

POPULATION STUDIED: Patients were eligible if they were aged 18 to 65 years and diagnosed with a migraine headache according to International Headache Society criteria. Subjects were recruited from 88 sites in 13 countries, but only those with a Migraine Disability Assessment Scale (MIDAS) of grade II, III, or IV were studied. Additional criteria included age at onset younger than 50 years, 1 to 8 attacks per month for the preceding 3 months, fewer than 10 nonmigraine headache days per month, and no change in preventive therapy during the trial. Participants were mostly women (83.2%), young (mean=37 years), and described their baseline disability as grade III or IV (mean=55%).

STUDY DESIGN AND VALIDITY: The study was conducted in an unblinded randomized parallel group design. During the 15-month period patients treated up to 6 moderate to severe migraines. The stratified group received care based on headache severity: Grade II was treated with aspirin 800 to 1000 mg plus metoclopramide 10 mg and grades III and IV with zolmitriptan 2.5 mg. The step care across attacks group all administered aspirin plus metoclopramide 10 mg as initial treatment. Therapy was escalated to zolmitriptan 2.5 mg in those that failed to respond in 2 of the first 3 attacks. Lack of response was defined as failure to reduce headache severity from moderate-severe to none-mild. All subjects in the step care within attacks group received the aspirin/metoclopramide combination as initial therapy but could add zolmitriptan if a response was not achieved within 2 hours. Efficacy and adverse effect data were self-reported on diary cards. Overall, the study was well conducted. Although the lack of treatment blinding is a potentially significant limitation, it may more closely approximate clinical practice. More importantly, the results may be different if other study drugs were chosen, and other agents are more commonly used in the United States. Finally, the results were not analyzed according to intention to treat and the dropout rate for the efficacy analysis was approximately 20%.

OUTCOMES MEASURED: The 2 primary outcomes were headache response at 2 hours and disability time per treated attack at 4 hours. Secondary end points included 1- and 4-hour responses, 2-hour pain-free response, and the occurrence of adverse events.

RESULTS: Headache response at 2 hours was significantly greater for stratified care than for either step care across attacks (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.31-2.12) or within attacks (OR=2.14; 95% CI, 1.66-2.77). These differences were mostly accounted for by the lack of response during the first 3 headaches (OR=2.91; 95% CI, 2.18-3.87) or within the first 2 hours of an attack, respectively. Disability time (from 0-4 hours) was also lower in the stratified care group than the step care across attacks group or the step care within attacks group. Again, there were no differences following treatment escalation in the step care groups. Adverse events were reported in approximately 14% of the attacks. They were more common in patients randomized to the stratified care group (19.5% vs 9.7% vs 13.1%). Those occurring less than 2% (asthenia, nausea, dizziness, paresthesias, and somnolence) were mild to moderate in severity and likely associated with zolmitriptan use. There was no difference in study withdrawal between treatment groups.