Migraine 'Step' Therapy Is Step Down in Relief
Stratified care, which used a patients migraine history as the basis for treatment and allowed immediate access to the migraine-specific agent zolmitriptan for severe cases, eliminated or sharply reduced headache pain 53 percent of the time. Similar pain relief was achieved 36 to 41 percent of the time with the step-care regimens, in which patients had to start with aspirin and the antiemetic drug metoclopramide and could use zolmitriptan only if the initial therapy did not reduce the pain. The findings were reported in the Nov. 22/29 issue of the Journal of the American Medical Association (PDF).
Patients who received stratified care were significantly more likely than patients in the step-care groups to be completely free of migraine pain within two hours of taking their assigned medication. Time endured at a less-than-full functional level was also significantly lower in the stratified-care group than in either step-care group.
These findings were obtained as part of the Disability in Strategies of Care (DISC) study, conducted from December 1997 to March 1999. The researchers assessed the level of pain relief obtained by each DISC study participant during as many as six migraine episodes of moderate or severe intensity. Patients whose pain was eliminated or reduced to a "mild" level were said to have responded to their assigned drug treatment.
A total of 1,062 adults, 18 to 64 years old, recruited from 88 medical centers in 13 countries agreed to participate in the DISC study. Over 80 percent of the participants were women.
Eligible patients had had one to eight migraine headaches, with or without aura, each month during the three months preceding the study. Patients who had used zolmitriptan or other triptan drugs within the past three months and those who suffered certain rare types of migraine were ineligible for the study.
At the start of the study, patients were each assigned a migraine disability assessment scale (MIDAS) grade based on the overall severity and frequency of the headaches experienced over the preceding three months. Only patients with MIDAS grades of IIdenoting mild or infrequent disabilitythrough IVdenoting severe disabilitywere eligible for the study.
Adults in each MIDAS class were randomly assigned to one of three treatment groups. A total of 354 adults were selected to receive stratified care, 352 were assigned to the "step care across attacks" group, and 356 received "step care within attacks." Efficacy data was obtained from 835 study participants, and data from 930 patients was used in an analysis of drug safety.
Drug therapy in the stratified-care group was given on the basis of patients initial MIDAS scores. During all their migraine attacks under study, patients in the stratified-care group with MIDAS scores of II received aspirin and metoclopramide while patients with grades III or IV used zolmitriptan.
Adults in the step-care-across-attacks group received aspirin and metoclopramide during their first three migraine episodes. Patients whose pain persisted above a mild level after two hours during at least two of their first three migraine attacks used zolmitriptan during the next three episodes. All other patients in the step-care-across-attacks group continued to use aspirin and metoclopramide to treat their next three migraine headaches.
In the step-care-within-attacks group, patients initially received aspirin and metoclopramide, then zolmitriptan after two hours if moderate pain persisted.
Initial drug dosages were the same in the three treatment groups, though the patients could take up to three doses of their assigned drug per headache. Aspirin was given in 800- to 1,000-mg doses and taken along with a 10-mg dose of metoclopramide. Study participants who used zolmitriptan received 2.5 mg-doses of the drug.
Patients in each treatment group were given diaries and asked to record the intensity of their migraine episodes and their response to treatment.
After the first three migraine attacks, when the step-care-across-attacks patients were permitted to use zolmitriptan, the level of pain relief achieved after two hours and the total disability time were similar between this group and the stratified-care group. Within the step-care-across-attacks group, 74 percent of the patients with initial MIDAS grades of IV, 69 percent of grade III patients, and 56 grades of grade II patients used zolmitriptan after their third migraine attack.
The study participants were allowed to use certain "rescue" medicationsanalgesics, sedatives, antiemetics, and nonsteroidal anti-inflammatory drugsfour hours after the onset of a migraine. Ergotamine could be used six hours after symptom onset, and triptans other than zolmitriptan 12 hours after the start of a headache.
The researchers did not provide data on the number of patients who used rescue medications during the study.
Drug safety was analyzed using data from 4,945 migraine attacks. Adverse events occurred during 14 percent of these episodesmore frequently among patients in the stratified-care group than in patients who received step care.
Most of the adverse events were classified as mild or moderate and considered typical of the adverse events known to occur during triptan therapy. About 3 to 4 percent of the patients in each treatment group withdrew from the study after having an adverse event.
The DISC study was funded by AstraZeneca L.P., manufacturer of the Zomig brand of zolmitriptan.