Conference Coverage
Although migraine prevalence is associated with sex, sex is not associated with response to IV migraine medication, according to research published online ahead of print October 21 in Headache. Age, however, is inversely associated with the efficacy of IV migraine medication and directly associated with the risk of adverse events.
An Analysis of Three Migraine Trials
Benjamin W. Friedman, MD, Associate Professor of Emergency Medicine at Albert Einstein College of Medicine in Bronx, New York, and colleagues examined data gathered during three emergency-department-based randomized comparative efficacy trials of various migraine medications to determine whether sex and age are associated with short-term headache relief, sustained headache freedom, or adverse medication effects. The medications studied in the trials included metoclopramide, an antiemetic dopamine antagonist; ketorolac, a nonsteroidal anti-inflammatory drug; dexamethasone, a corticosteroid; and valproate, an antiepileptic drug. In each of the clinical trials, patients presenting to an emergency department with acute migraine were randomized to treatment with one or a combination of the IV drugs.
Eligible patients had an acute headache that fulfilled all International Classification of Headache Disorders criteria for migraine without aura. Patients were not excluded for prolonged duration of headache, however. Nor were patients required to have had more than one similar previous headache. Dr. Friedman and colleagues assessed pain levels and medication side effects at baseline, at one and two hours after medication administration, and by telephone at 24–48 hours after discharge from the emergency department. Patients described their pain as none, mild, moderate, or severe.
The researchers chose short-term headache relief (ie, a headache level of mild or none within one hour of treatment) and sustained headache freedom (ie, a reported headache level of none in the emergency department and a period of headache freedom of at least 24 hours after discharge) as their efficacy end points. The investigators’ third outcome was side effects.
For the primary analysis, Dr. Friedman and colleagues used the population’s median age to separate participants into an older and a younger group. In a secondary analysis, they considered age as continuous data.
Nausea Was More Common in Older Patients
The three original studies included 884 participants. The investigators found no differences between men and women in terms of age, race, duration of headache, or presence of aura. Compared with men, women were more likely to be nauseated (56% vs 41%) and to report severe pain at baseline (69% vs 59%). Similarly, patients age 36 or older were more likely to be nauseated (57% vs 50%) and to report severe pain at baseline (72% vs 64%) than patients younger than 36. “We are the first to report [this finding],” said Dr. Friedman.
Men and women were approximately equally likely to report short-term and sustained headache improvements and adverse events. Patients age 36 or older, however, were less likely than younger patients to respond favorably to headache medication and more likely to have adverse events. Most of the difference in efficacy outcomes between older and younger patients can be explained by differential response to metoclopramide regimens, according to the authors.
Bivariate analyses performed for various medication types indicated that adults age 36 or older were less likely to respond to combinations of metoclopramide and diphenhydramine. Age was not associated with the efficacy of ketorolac or valproate, however. “Because the bulk of our data comes from patients who received metoclopramide, these data do not necessarily translate to other medication classes,” said Dr. Friedman. Although adults older than 35 may be less likely to respond to metoclopramide regimens, it is uncertain that they are more likely to respond to alternate treatment regimens, he added. “Therefore, one should not reject metoclopramide in adults older than 35 based solely on these data.”
The higher rate of adverse events in older patients primarily resulted from a disparity in response to dexamethasone. Adults older than 35 who received dexamethasone had an adverse event rate of more than 50%. “Because the benefit of dexamethasone for patients with acute episodic migraine is relatively modest, clinicians may wish to avoid administering this medication to these patients,” said Dr. Friedman.
After the investigators performed multivariate logistic regression modeling, they found that sex did not meaningfully influence the association between age and the study outcomes. Likewise, age did not influence the lack of association between sex and the study outcomes.
Bioavailability May Decline With Age
The reasons for age-related differences in the efficacy of IV migraine medication are a matter of debate. One hypothesis is that age-related alterations in pharmacodynamics may affect the drugs’ bioavailability, said the authors. In addition, previous research indicates that endogenous pain modulation declines with age and affects the middle-aged and the elderly. Another potential explanation involves the psychologic response to investigational medicine. In outpatient triptan trials, middle-aged adults with migraine were less likely to respond to oral placebo than younger adults were. “Thus, these data may not represent a difference in true efficacy at all, but rather a diminished expectation of treatment benefit,” said Dr. Friedman.
