ABORTIVE TREATMENT FOR ACUTE MIGRAINE
Brent Wiederholt
Common Health Problems
March 5, 2014
CAT PAPER
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ABORTIVE TREATMENT FOR ACUTE MIGRAINE
SCENERIO:
A female patient presents for a throbbing headache that she reports is causing vomiting, she
reports needing to wear sunglasses to help with the increased pain caused by bright lights. She also
reports a history of migraines that usually respond to Excedrin but this time there is no relief. How do
you proceed?
DEFINITION:
Migraine is defined by a headache that is accompanied by any two of the following descriptions:
unilateral, worsening with movement, accompanied by photophobia or phonophobia; and presence of
any one of the following symptoms: throbbing quality, moderate to severe nausea, or vomiting.
Approximately 12% of the population experiences an average of 18 migraines per year. (McCance, K. L.,
2010) Migraine headaches are ranked in the top 20 most common causes of disability, equal to diabetes
mellitus.
Treating an acute migraine can be challenging because of substantial rates of nonresponse to
medications and difficulty in predicting individual response to a specific agent or dose of medication.
Confounding migraine treatment are the many different drug classes that seem to have an effect on
various migraines. Triptans, dopamine antagonists, metoclopramide, prochlorperazine, and others,
including opiates, have been well studied for single agent treatment. While some of these agents have
shown greater efficacy than others, there is still a significant amount of migraine episodes that fail to
respond to treatment or result in a rebound headache. Combination pharmacologic therapy has not
been well studied for the treatment of acute migraine headaches.
QUESTION:
In those patients presenting with acute migraine, is combination therapy more effective than
single agent therapy, in aborting a migraine headache.
STUDIES:
Promethazine Plus Sumatriptan in the Treatment of Migraine: A Randomized Clinical Trial
This study compared a combination of sumatriptan 50 mg and promethazine 25 mg with
sumatriptan 50 mg plus placebo. This was a multicenter, randomized, double-blind trial conducted at 5
university research centers. The study used 242 patients who met the criteria for the study. They were
randomly placed in two groups of 121 participants in each group.
The study showed that the addition of promethazine is significantly more effective in acute
migraine treatment, with 39.6% being headache free at 2 hours, compared to 26.3% with placebo.
Headache improvement at 2 hours was 62.2% to 37.2%, in favor of the promethazine group. The
incidence of headache recurrence from 2 to 48 hours was 15% for the promethazine group and 26.6%
for the placebo group. The only adverse event was somnolence, with the promethazine group being
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ABORTIVE TREATMENT FOR ACUTE MIGRAINE
32.2% and the placebo group 7%. Somnolence is viewed as a benefit in migraine treatment. Nausea was
1% and 8%, in the promethazine and placebo groups, respectively. (Asadollahi, S., 2013)
Strengths of the study included the randomization of patients and the equal baseline of pain.
The study size was large enough and the significance strong enough to be utilized for evidence based
guidelines. Weaknesses could be seen as only comparing promethazine with placebo. The study should
have compared both sumatriptan and promethazine individually to placebo to better evaluate the
synergy effect. Because of the limited studies involving combination therapy, this should be viewed as
Class B evidence. The P value of this study was less than .001.
Pharmacological Synergy: The Next Frontier on Therapeutic Advancement for Migraine
This review compared the combination of sumatriptan 50 mg and naproxen 500 mg with both
agents independently and placebo. The study showed a significant outcome for the combination
therapy, with a sustained pain response of 46% for the combination, and 29% for the sumatriptan, 25%
for naproxen, and 17% for placebo. The pain free response was also significantly greater for the
combination therapy, at 25%, compared to 11, 12, and 5%, respectively. (Blumenfeld, A., 2011)
The strength of this review was that it compared the combination therapy with each agent
individually and against placebo. This allows the extrapolation of the data to determine the true
synergistic affect. The study also examined over 5,000 participants, adding to the significance of the
results. The results are Class B evidence because of the limited studies in this area. The P value of the
utilized studies was .01.
CLINICAL BOTTOM LINE:
Both of these reviews were very well executed. They both found significance in the positive
outcome of using combination therapy for acute migraine treatment. Further research should be done
in utilizing NSAIDS, triptans, steroids, phenothiazines, and other agents in the abortive treatment of
migraine. Some of the NSAIDS and phenothiazines individually are shown to be as effective as the
triptans, and the addition of steroids is shown to reduce recurrence rate. (Blumenfeld, A., 2011)
Combination therapy should be utilized in the treatment of acute migraine headache. Due to the
mixed presentation of migraine headaches and the resistance to improvement with single agents, dual
therapy should be utilized as it is associated with faster pain relief, longer duration of pain relief, and a
lower incidence of rebound headache.
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References:
Asadollahi, S., Heidari, K., Vafaee, R., Forouzanfar, M., Amini, A., and Shahrami, A. (2013) Promethazine
Plus Sumatriptan in the Treatment of Migraine: A Randomized Clinical Trial. Cochrane Database
of Systematic Review. Doi: 10.1111/head.12259
Blumenfeld, A., Gennings, C., and Cady, R. (2011) Pharmacological Synergy: The Next Frontier on
Therapeutic Advancement for Migraine. Cochrane Database of Systematic Review. Doi:
10.1111/j.1526-4610.2011.02058.x
McCance, K. L., Huether, S. E., Brashers, V. L., and Rote, N. S. (2010) Pathophysiology The Biologic Basis
for Disease in Adults and Children. Mosby Elsevier. Maryland Heights, MO.
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