Migraine or severe headache affected one-fifth of women and one-tenth of men in 2015 and
is one of the leading causes of disability in the world. Over one million visits to
emergency departments (ED) in the US are due to migraines. Migraine, previously believed
to be a vascular disorder, is caused by inflammation due to vasodilation in the meninges
secondary to the release of vasoactive neuropeptides by stimulation of the trigeminal
nerve. This inflammation can result in symptoms such as headache, nausea, vomiting,
dizziness, photophobia and phonophobia.
Despite migraine being a common disorder, there has yet to be a cure. Several classes of
medications have been studied for the treatment of migraine. Recently, conventional
therapy has shifted to the use of antidopaminergics including prochlorperazine,
metoclopramide and haloperidol, nonsteroidal anti-inflammatory drugs (NSAIDs) such as
ibuprofen and naproxen, and triptans, sumatriptan being the most commonly utilized.
5Although intravenous opioids have historically been the most common treatment for
migraines, their use has fallen out of favor due to their association with increased
recurrence of headaches and ED visits, abuse potential, and most recently severe
intravenous opiate shortage. Alternative treatments include ketamine, propofol,
dihydroergotamine and magnesium.
Magnesium is an intracellular cation that has been associated with both the function of
serotonin and regulation of vascular tone, which are both mechanisms that implicate its
role in the treatment of migraine. Intravenous magnesium sulfate has been studied as a
treatment for migraine compared to placebo, metoclopramide and prochlorperazine. These
studies have shown that magnesium is well-tolerated with a good safety profile and may be
efficacious in the treatment of migraine. Metoclopramide, prochlorperazine and magnesium
have been recommended in clinical practice guidelines and have become routine standard of
care for treatment of migraine in this emergency department. However, no trial has
evaluated these modalities simultaneously in the same population. The purpose of our
study is to compare the relative efficacy for magnesium, metoclopramide, and
prochlorperazine in the treatment of headache and migraine.
Via monthly block randomization, patients will be given one of three guideline
recommended study drugs. Allocation will be concealed by a pharmacist (not participating
in the rest of the study) solely designated to choose which drug will be the assigned
study drug for each month. The pharmacists, physicians, and nurses participating in
administration of the medications will be blinded to which drug is being administered
during each month. Metoclopramide, prochlorperazine and magnesium have been recommended
in clinical practice guidelines and have become routine standard of care for treatment of
migraine in this emergency department. All three study drugs will be stored in the
investigational medication refrigerator located in the main pharmacy. A pharmacist on
duty in the emergency department will obtain the medication from the refrigerator and
deliver it to the bedside nurse who is actively caring for the patient after an order
from the physician.
The primary outcome of this study will be mean change in pain from baseline to 30 minutes
after initiation of infusion (as defined on a 11-point Numeric Rating Scale. Secondary
endpoints include mean change in pain from baseline to 60 minutes and 120 minutes after
initiation of infusion (as defined on a 11-point Numeric Rating Scale), time to emergency
department discharge, and adverse effects due to administration of study drug
(hypotension, flushing, akathisia, dystonia, nausea, vomiting, dizziness, drowsiness,
other self-reported adverse effects).