Acute Migraine Treatment.6 PDF

Review Article
Acute Migraine
Treatment
Werner J. Becker, MD
ABSTRACT
Purpose of Review: This article provides a systematic, evidence-based approach to
acute medication choices for the patient with migraine.
Recent Findings: Recent clinical trials, meta-analyses, and practice guidelines have
confirmed that four nonsteroidal anti-inflammatory drugs (NSAIDs) with randomized controlled trial evidence for efficacy in migraine (ibuprofen, naproxen sodium,
diclofenac potassium, and acetylsalicylic acid) and seven triptans (sumatriptan, rizatriptan,
eletriptan, zolmitriptan, almotriptan, frovatriptan, and naratriptan) are appropriate medications for acute migraine treatment. Dihydroergotamine (DHE) is also suitable for
selected patients.
Summary: NSAIDs and triptans are the mainstays of acute migraine therapy, and
antiemetic drugs can be added as necessary. Opioids and combination analgesics
containing opioids should not be used routinely. Patient-specific clinical features should
help guide the selection of an acute medication for an individual patient. Acute
medications can be organized into four treatment strategies for use in various clinical
settings. The acetaminophen-NSAID strategy is suitable for patients with attacks of
mild to moderate severity. The triptan strategy is suitable for patients with severe
attacks and for those with attacks of moderate severity who do not respond well to
NSAIDs. The refractory migraine strategies may be useful for patients who do not
respond well to the NSAIDs or triptans alone and include using triptans and NSAIDs
simultaneously in combination, DHE, and rescue medications (eg, dopamine antagonists, combination analgesics, and corticosteroids) when the patients usual medications fail. Strategies for patients with contraindications to vasoconstricting drugs include
use of NSAIDs, combination analgesics, and dopamine antagonists.
Acetaminophen is the safest acute migraine drug during pregnancy, and acetaminophen with codeine is also an option. Sumatriptan may be an option during pregnancy for selected patients and is compatible with breast-feeding.
Address correspondence to
Dr Werner J. Becker, Foothills
Hospital, Division of Neurology,
12th Floor, 1403 29th Street NW,
Calgary, AB, T2N 2T9, Canada,
wbecker@ucalgary.ca.
Relationship Disclosure:
Dr Becker has served on the
medical advisory boards of
Allergan, Inc; Amgen Inc;
electroCore Medical LLC; and
Tribute Pharmaceuticals
Canada, Inc, and the clinical
trial steering committee of
St. Jude Medical, Inc. He
has received personal
compensation for speaking
engagements from Allergan,
Inc; EMD Serono, Inc; Teva
Pharmaceutical Industries Ltd;
and Tribute Pharmaceuticals
Canada, Inc, and for the
development of educational
materials for Allergan, Inc.
Unlabeled Use of
Products/Investigational
Use Disclosure:
Dr Becker discusses the
unlabeled/investigational
use of butalbital, codeine,
dexamethasone, dexketoprofen,
dimenhydrinate, domperidone,
ketorolac, metoclopramide,
morphine, oxycodone,
prednisone, prochlorperazine,
and tramadol for the acute
treatment of migraine.
* 2015, American Academy
of Neurology.
Continuum (Minneap Minn) 2015;21(4):953972.
INTRODUCTION
Pharmacologic migraine treatment can
be divided into two categories: acute
migraine drug treatment for individual
attacks and prophylactic (preventive) drug
treatment. It is critical that patients understand the differences between these two
categories as the medications used are
quite different. Also, while daily medication use is essential for successful preventive treatment, the frequency of use of
acute medications must be limited to
avoid medication-overuse headache.
Continuum (Minneap Minn) 2015;21(4):953972
Use of acute medications among individuals with migraine is almost universal. More than 90% of migraine sufferers
in the general population use one or more
acute migraine medications.1 Treating
moderate or severe migraine attacks effectively is important. Migraine attacks
cause significant disability. Based on ictal
disability during the migraine attack alone,
the World Health Organization (WHO)
ranks migraine eighth among all disorders
causing years of life lived with disability.2
Effective acute medication use should
www.ContinuumJournal.com
Copyright American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
953
Acute Migraine Treatment

KEY POINTS
h Patients need to
understand the
difference between
acute and preventive
migraine medications.
h The cost of migraine to

society, considering
both direct and indirect
costs, is enormous. A
European study found
that the cost of
headache to society
exceeded the costs of
many other neurologic
disorders, including
stroke, multiple
sclerosis, and
Parkinson disease.
have the potential to markedly reduce

the disability caused by migraine attacks by
shortening attack duration and reducing
attack severity.
The cost of migraine to society, considering both direct and indirect costs
(eg, missed work) is enormous. A
European study found that the cost of
headache to society greatly exceeded the
costs of many other neurologic disorders,
including stroke, multiple sclerosis, and
Parkinson disease.3 Good acute pharmacologic migraine treatment might be expected to reduce these costs.
For some individuals, migraine appears to be a progressive disorder. Approximately 1% of the general population
has chronic migraine, a disabling migraine
syndrome in which individuals suffer from
headache on 15 or more days per month
for at least 3 months.4 Approximately 12%
of the general population has migraine,5
and essentially all individuals with chronic
migraine have a prior history of episodic
migraine. Risk factors that predispose
patients to the development of chronic
migraine include obesity, snoring, caffeine use, allodynia, depression, stressful
situations, acute medication overuse,
head injury, and suboptimal acute treatment of individual attacks. Peripheral
and central sensitization of pain pathways due to repeated migraine attacks
may play a role in the pathophysiology
of chronic migraine, and, indeed, a high
migraine attack frequency is a major
risk factor for its development.6
APPROACH TO ACUTE MIGRAINE
TREATMENT
Many medications are used for acute
migraine treatment, and both the practitioner and the patient need to have an
organized approach to medication choice.
Three basic approaches or strategies have
been identified based upon attack severity
and migraine-related disability.7
Stratified Approach
In the stratified approach, the medication chosen for a given patient is based
954
on migraine attack severity and the resulting disability. Thus, a triptan might be
prescribed as initial therapy for patients
with severe disabling attacks that often
render them unable to function, while a
nonsteroidal anti-inflammatory drug
(NSAID) might be chosen as initial therapy for a patient with less severe attacks.
This approach attempts to try the best
medication for the patient first. Neurologists should keep in mind that by the
time patients with migraine consult, they
have invariably tried multiple over-thecounter simple and combination analgesics, including NSAIDS. Therefore, a
stratified approach will be necessary for
patients who present to a neurologist.
Step-Care-Across-Attacks
Approach
In the step-care-across-attacks approach,
a less expensive medication or one with
greater perceived safety or fewer side effects is chosen first for a patient. If this is
ineffective, other medications are tried in
turn for subsequent attacks as previously
used medications fail. This approach
may result in several failed therapeutic
trials with simple analgesics and NSAIDs
before an effective medication is found
for the patient with relatively severe
migraine attacks. It may also result in a
patient becoming a lapsed consulter
as patients may feel little can be done
for them. They may then rely on overthe-counter nonprescription medications, often with poor therapeutic results.
In practice, given the availability of many
medications without prescription, many
patients have already tried a number of
medications before consulting a physician for their headaches. Thus, they may
be well advanced along a step-care-acrossattacks approach at the time of consulting.
Step-Care-Within-Attack
Approach
With the step-care-within-attack approach,
a patient takes a simple analgesic (eg,
August 2015
acetaminophen or an NSAID) at migraine

attack onset and then steps up later in
the course of the attack to another medication class (eg, a triptan) if the initial
medication fails to provide adequate relief. This approach may be effective for
patients with attacks that build up slowly
or for patients with attacks of variable
severity, but all acute medications for migraine generally work better when taken
early in the attack. The second moreeffective medication may also not work
well for the patient if it is taken later in
the attack. Patients using the step-carewithin-attack approach need to monitor
their success rate with their initial medication, preferably with a headache diary,
and if the success rate is low, they would
be well advised to go directly to the more
effective medication early in their attacks.
GENERAL PRINCIPLES OF ACUTE
MIGRAINE TREATMENT
Practitioners need to consider several
principles of acute migraine treatment
when recommending an acute medication for a specific patient, which include
the following:
1. Early treatment in the attack
should be a goal for most patients.
All acute medications, including
triptans,8 tend to be more effective
if taken early in the attack compared
to when the attack has progressed
or is fully established.
2. The response of a patient to an acute
medication cannot be predicted
with certainty. The physicians first
recommendation may not be effective,
and patients need to understand
that other options are available.
Patient follow-up is often critical in
achieving a successful outcome.
3. An appropriate treatment approach
needs to be chosen, as discussed
above. Some patients have attacks
of differing severity and may need
more than one acute treatment
option for best results.
4. An appropriate medication
formulation should be chosen
based on the characteristics of the
patients migraine attacks. Some
patients may require more than
one formulation. Attack features
to consider include:
& For patients without significant
nausea, regular oral tablets may
be a good choice, but orally
disintegrating tablets (wafers),
nasal sprays, and injections may
all be appropriate options. Among
the triptans, subcutaneous
sumatriptan has the highest
response rate,9 but also produces
the most discomfort and is
associated with the highest rate
of side effects. The triptan nasal
sprays, because of partial
absorption through the nasal
mucosa, particularly with
zolmitriptan nasal spray, may
have a faster onset of action than
the tablets.
& The triptan orally disintegrating
tablets (wafers) can be helpful
for patients with mild nausea, or
when nausea is exacerbated by
taking fluids, and allow for early
treatment even if water is not
available. They are not absorbed
through the buccal mucosa and,
therefore, do not have a faster
onset of action than regular tablets.
& For patients with greater degrees
of nausea and for those who may
vomit later in the attack, the triptan
nasal sprays can be very useful.
However, the dysgeusia associated
with nasal sprays may exacerbate
nausea and should be monitored.
& For migraine attacks that build
up very rapidly and for those
that are fully developed upon
awakening, an injectable
formulation (eg, injectable
sumatriptan) often has the
greatest chance of providing
KEY POINTS
h For patients with

relatively severe and
disabling migraine
attacks, a stratified
approach to acute
medication choice,
which tries the best
drug first, is often the
best approach.
h When migraine attacks

usually build up to a
moderate or severe
intensity, acute
medications are generally
more effective when
taken early in the attack
while the pain is still
mild, but care must be
taken to avoid medication
overuse in patients with
frequent attacks.
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KEY POINTS
h Although most patients

prefer an oral medication,
a nonoral formulation,
particularly subcutaneous
sumatriptan, may be much
more effective for attacks
with early vomiting.
h Opiate-containing
combination analgesics
should not be used
routinely for migraine
treatment, as better
options are available
for most patients.
956
relief. This is particularly true if

the patient tends to vomit early
in the attack.
& For less severe attacks that build
up rapidly or if patients desire a
faster onset of action, several oral
formulations that are designed to
deliver a fast onset of action can
be recommended. These include
diclofenac powder for oral
solution,10 solubilized
(liquid-containing) NSAID
formulations (eg, ibuprofen),
effervescent acetylsalicylic acid
(ASA), and the sumatriptan
fast-dissolving tablet.
5. Two or more acute medications can
be combined if necessary. The most
studied combination has been
sumatriptan and naproxen, and the
combination is more effective than
either drug alone.11 Metoclopramide
can also be added to a triptan or
NSAID or a combination of both to
treat nausea and may also enhance
absorption of the acute migraine
drug. Caffeine enhances the
effectiveness of analgesics, but
needs to be balanced against negative
effects such as interference with
sleep and caffeine-withdrawal
headache caused by excessive use.
6. Acute medication overuse needs to
be avoided. Individuals with
migraine appear to be particularly
susceptible to exacerbation of their
headache syndrome by the frequent
use of analgesics. Frequent ergotamine
and triptan use can also lead to
increased headache frequency. Use
of acetaminophen or NSAIDs on 15 or
more days per month, or combination
analgesics, opioids, ergotamines, or
triptans on 10 or more days per month
are considered to place patients at risk
for medication-overuse headache.12
7. Opiates and opiate-containing
combination analgesics should
not be used for the routine
treatment of migraine. These

medications, although helpful for
some patients, are less effective
than many of the other medications
available and tend to lead to
escalation in frequency of use and
medication-overuse headache.
MEDICATION CHOICE
Randomized, double-blind controlled-trial
evidence exists that a number of medications are effective for acute migraine
treatment. When choosing an appropriate acute medication for a specific patient, an organized approach is important.
Organizing the available medications into
a small number of strategies that can be
applied to a specific clinical situation may
be helpful (Table 1-1).13 This approach
is discussed further below.
Antiemetics
Metoclopramide (usual dose 10 mg, may
be used up to 4 times a day) has the
strongest evidence for efficacy in migraine, and some evidence exists for
the use of domperidone (not available
in the United States; usual dose 10 mg,
may be used up to 4 times a day). Although metoclopramide poses some
risk of extrapyramidal side effects and
domperidone has been reported to cause
QT prolongation, these are uncommon
with the intermittent oral dosing used to
treat migraine attacks. Many patients use
dimenhydrinate because of its availability
without prescription, but dimenhydrinate
is a complex formulation and contains
both an antihistamine (H1 antagonist)
and a stimulant (theophylline derivative)
The medication has abuse potential, and
its efficacy in treating migraine-related
nausea lacks evidence. Metoclopramide
and domperidone are better choices.
For refractory patients, prochlorperazine
can also be used, both orally (usual dose
10 mg, may be given up to 4 times a day)
or by suppository (dosage range 10 mg to
25 mg, maximum daily dose 50 mg), but
August 2015
KEY POINTS
h When an antiemetic is
TABLE 1-1 Acute Migraine Treatment Strategies

Strategy
Medications
Acetaminophen and nonsteroidal

anti-inflammatory drug strategy for
attacks of mild to moderate severity
Acetaminophen (primarily for

milder attacks)
necessary, a dopamine
antagonist, in particular
metoclopramide, is
often the best choice.
h The nonsteroidal
Acetylsalicylic acid
anti-inflammatory drugs
with the best evidence
for efficacy for acute
migraine treatment
are acetylsalicylic acid,
ibuprofen, naproxen
sodium, and
diclofenac potassium.
Ibuprofen
Naproxen sodium
Diclofenac potassium
Triptan strategy for moderate and
severe attacks
Sumatriptan
Rizatriptan
Eletriptan
Zolmitriptan
Almotriptan
Frovatriptan
Naratriptan
Refractory migraine strategies
Triptan and nonsteroidal

anti-inflammatory drug combinations
Dihydroergotamine
Various rescue medications
(eg, dopamine antagonists)
Combination analgesics without opioids
Combination analgesics with opioids
(not for routine use)
Strategies for patients with

contraindications to
vasoconstricting drugs
Nonsteroidal anti-inflammatory drugs

Dopamine antagonists
Combination analgesics without opioids
Combination analgesics with opioids
(not for routine use)
has more extrapyramidal side effects.

Metoclopramide, domperidone, and
prochlorperazine can each be added
to all the acute treatment strategies
discussed below.13
AcetaminophenNonsteroidal
Anti-Inflammatory Drug
Strategy for Attacks of Mild to
Moderate Intensity
Acetaminophen and four NSAIDs (ASA,
ibuprofen, naproxen sodium, and diclofenac
potassium) have good evidence supporting their use for migraine. Oral ketorolac
does not have randomized controlled trial
evidence, although parenteral ketorolac
has been studied in the emergency department setting. The preferential use of
oral medications with a sound evidence
base is prudent.
Acetaminophen has the advantage
of less gastric irritation, and because it
does not block prostaglandin synthesis
in platelets, it does not affect platelet
957

KEY POINT
h Specialized nonsteroidal
anti-inflammatory drug
formulations with a
more rapid onset of
action than regular
tablets are available.
958
function. Acetaminophen is considered

less effective than the NSAIDs and suitable for relatively mild migraine attacks.
The recommended dose of acetaminophen for migraine is 1000 mg per dose,
and, because of its short half-life (2 to
3 hours), patients may need to repeat this
dose. It is important that the daily dose
be kept below 4000 mg in a 24-hour
period to avoid hepatotoxicity.
Ibuprofen is likely the most commonly used NSAID by individuals with
migraine. Good evidence for efficacy
exists, with a number needed to treat of
3.2 for headache relief at 2 hours (pain
reduced to mild or no pain) and 7.2 for
pain free at 2 hours.14 A solubilized form
(liquid-containing capsules) has a somewhat faster onset of action as compared
to regular tablets. Ibuprofen also suffers from a short half-life (2 hours), so
repeated dosing may be necessary. In
controlled trials, higher doses were no
more effective than the 400-mg dose,
which is the most appropriate dose
(maximum daily dose 2400 mg). Ibuprofen may cause less gastric irritation than
ASA and is at least as effective. Although
the response of an individual patient to
any particular drug cannot be predicted,
ibuprofen appears to be preferable to
ASA for most patients.
Diclofenac potassium is another NSAID
with a rapid onset of action. Maximal
plasma concentrations are achieved in
under an hour with the tablet and in
less than 15 minutes with the powdered
formulation for oral solution.10 Numbers needed to treat for the 2-hour painfree end point (at least for the powder
formulation) are similar to ibuprofen. Like
ibuprofen, the half-life is short (2 hours).
The usual dose of diclofenac potassium
is 50 mg; the maximum daily dose for
diclofenac potassium tablets is 150 mg.
For diclofenac powder, one dose per
day is recommended.
Naproxen sodium, with its long duration of action (half-life of 14 hours) is
unique among the NSAIDs commonly

used for acute migraine treatment. However, naproxen sodium has a slower
onset of action, and the number needed to treat for the 2-hour pain-free end
point is 15, which is higher than for the
other NSAIDs. It has a favorable cardiovascular risk profile compared to
ibuprofen and diclofenac potassium,
although the relevance of this to the intermittent dosing used by patients with
migraine is unclear. The usual dose is
500 mg or 550 mg, although one study
suggested the 825-mg dose was more
effective.15 Total daily dose should not
exceed 1375 mg. The naproxen sodium
salt should be used for faster absorption.
ASA is usually used in doses of
975 mg to 1000 mg (maximum daily
dose 4000 mg). Effervescent ASA has a
faster onset of action than regular tablets and has shown efficacy similar to
that of sumatriptan 50 mg.16 Including
its active salicylate metabolite, ASA has
a relatively long half-life of 6 hours. Like
all the NSAIDs and acetaminophen, the
medication can be combined with metoclopramide 10 mg.
Other NSAIDs may also be effective,
but cannot be recommended because
of a lack of good randomized controlled
trials. This includes ketorolac, although
ketorolac is of some interest because it
combines rapid absorption (maximum
plasma levels occur in less than 1 hour)
with a relatively long half-life (5 hours).
The usual dose is 10 mg, and the maximum daily dose 40 mg; it is recommended that patients not use ketorolac
for more than 5 to 7 consecutive days because of potential renal and gastrointestinal toxicity.
Clinical trials suggest that the NSAIDs
can be effective even in severe migraine
attacks, which has been recognized by
several guidelines.17,18 However, clinical
experience indicates that for many patients with severe migraine attacks, the
triptans are often a better choice. For a
August 2015
summary of the acetaminophen-NSAID

strategy, see Table 1-2.
Triptan Strategy for Moderate
and Severe Attacks
The triptans are considered second line
by some, after the NSAIDs, but perhaps
the only reason for this approach is that
they are considerably more expensive
than the NSAIDs. The triptans have been
proven to be very safe in patients free of
vascular disease and are generally well
tolerated.19 For many patients with severe migraine attacks, these medications
should be considered first line. When patients are usually NSAID responsive but
have occasional treatment failures, a triptan
can be prescribed as a rescue medication.
In fact, when an NSAID is prescribed for
a patient with relatively severe migraine
attacks, a triptan could be preemptively
prescribed as a rescue medication in case
the NSAID is not satisfactory. If necessary,
the triptan could become the patients
primary acute medication.
The triptans have become the most
used migraine-specific medications because of their pharmacologic specificity,
TABLE 1-2 Acetaminophen and Nonsteroidal Anti-inflammatory a,b

Drug Strategy for Attacks of Mild to Moderate Severity
Medication
Usual Dose and Maximum

Dose per Dayc
Acetaminophen (primarily for

milder attacks)d
1000 mg
Ibuprofen tablets
400 mg
Maximum 4000 mg/d
Maximum 2400 mg/d

Ibuprofen solubilized (liquid) tablets
400 mg
Maximum 2400 mg/d
Diclofenac potassium tablets
50 mg
Maximum 150 mg/d
Diclofenac powder for oral solution
50 mg
Maximum single dose/d
recommended
Naproxen sodium
500Y550 mg (up to 825 mg)

Maximum 1375 mg/d
Acetylsalicylic acid
975Y1000 mg
Maximum 4000 mg/d
Effervescent acetylsalicylic acid
975Y1000 mg
Maximum up to 2000 mg/d
recommended
For acetaminophen and all nonsteroidal anti-inflammatory drugs, limit use to 14 days a month or
fewer to avoid medication-overuse headache.
Patients may experience gastrointestinal irritation, increased blood pressure, and renal toxicity with
excessive use of all nonsteroidal anti-inflammatory drugs. Avoid the use of these drugs if gastrointestinal
ulcers are present or if the patient has asthma with acetylsalicylic acid.
c
Dosages are for adults. For acute migraine treatment, only one or two doses are usually recommended.
d
Liver toxicity with excessive dose or concomitant use of alcohol.
b
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KEY POINTS
h Because they are highly

specific medications,
the triptans offer an
excellent clinical
benefit-to-side-effect
ratio for many patients.
h Despite the pharmacologic

similarities among the
various triptans, individual
patients may respond
much better to one triptan
than another.
960
which usually allows them to be used

in adequate doses without major side
effects. They are 5-hydroxytryptamine
(5-HT1B, 5-HT1D) receptor agonists, and
their antimigraine actions are mediated
mainly through these receptors. Triptans
have a great advantage over ergotamine
and dihydroergotamine (DHE) in that
these older drugs affect a number of
other receptor types that often produce side effects, in particular nausea,
at therapeutic doses.
All seven triptans currently available
have strong evidence for efficacy. Although they largely share a common
mechanism of action, some patients will
greatly prefer one triptan over another
because of greater effectiveness, fewer
side effects, or both. This phenomenon
remains unexplained, although it may
relate to the different genetic factors that
may underlie the migraine disorder in
different patients. In general, there is no
best triptan overall, and for any given
patient, the best triptan in the one that
is most effective and best tolerated by
that patient. If a patients response to a
specific triptan is not optimal, then several other triptans should be tried for
subsequent attacks as they may work
much better. However, not all patients
with migraine respond to the triptans,
and some will need other options.
Triptan choice. Despite their similarities, pharmacokinetic and other
differences exist between the various triptans and their formulations, which have
significant clinical implications. Sumatriptan 6 mg administered by subcutaneous injection has the lowest number
needed to treat for any triptan formulation (2.3 for 2 hours pain free). Among
the oral triptans, a recent meta-analysis
found that eletriptan 40 mg and rizatriptan
10 mg provided the highest pain-free
rates at 2 hours, and eletriptan also provided the highest 24-hour sustained painfree rate (no recurrence of headache
for 24 hours).20
Some attempt can be made to tailor

triptan choice to the characteristics of
the patients migraine attacks. If patients awaken with full-blown attacks or
if they tend to vomit early in the attack,
subcutaneous sumatriptan 6 mg may be
the best choice; it is also a good choice
for patients who do not respond well to
other triptan formulations (Case 1-1).
For patients with lesser degrees of nausea, sumatriptan nasal spray 20 mg or
zolmitriptan nasal spray 5 mg may be
good choices. The nasal sprays may also
be helpful for any patients who do not
respond well to the oral triptans. If taking
oral fluids exacerbates nausea, the orally
dissolving tablets (wafers) (rizatriptan
10 mg and zolmitriptan 2.5 mg) may
be a good choice. The wafers also allow
for early treatment when water is not
readily available. The wafers are not absorbed through the oral mucosa, however, and do not have a faster onset of
action than the standard oral tablets. For
most patients, the standard oral tablets
work well. For patients with attacks that
build up rapidly to a high intensity, speed
of action and a high response rate are
important. For these, rizatriptan 10 mg
and eletriptan 40 mg might be the most
useful oral triptans. Zolmitriptan nasal
spray 5 mg should also be considered,
particularly if significant nausea is present. Of the zolmitriptan administered
intranasally, 30% is absorbed through the
nasal mucosa and, therefore, enters the
blood stream very rapidly. Zolmitriptan
nasal spray 5 mg provides pain relief in
some patients (superiority over placebo)
within 15 minutes, and pain-free responses exceed placebo at 30 minutes.21
If frequent headache recurrence after initial
successful treatment is an issue, eletriptan
40 mg and frovatriptan 2.5 mg are good
choices as both have a longer half-life
than most triptans and a lower headache
recurrence rate.22 If side effects are an
issue, almotriptan 12.5 mg may be better
tolerated but still offers a good response
August 2015
Case 1-1
A 34-year old-woman who had experienced episodic migraine attacks since her teenage years
presented for a neurologic evaluation, where she reported having about four attacks per month,
most of which occurred during the day and responded well to oral rizatriptan 10 mg if treated shortly
after attack onset. She reported waking once a month with a fully developed migraine attack and
vomiting within an hour of awakening. These attacks did not respond to oral rizatriptan, and she
was unable to go to work on those days. She had no significant past medical history. Neurologic
examination was normal.
She was advised to use sumatriptan 6 mg by subcutaneous self-injection for the severe attacks that
were present on awakening and to continue with oral rizatriptan for other attacks. She was prescribed
oral metoclopramide 10 mg tablets and advised to take one tablet with the sumatriptan to assist in
managing her nausea. She was also advised that if nausea and vomiting remained a problem, another
option for treatment of her nausea would be prochlorperazine suppositories (10 mg to 25 mg).
Comment. Subcutaneous sumatriptan remains the triptan with the highest response rate in
treating migraine attacks and is particularly useful for patients with early vomiting during the attack.
Most patients prefer an oral medication if possible; thus, it can be useful both in terms of patient
convenience and cost to make more than one formulation available. Patients can then tailor their
treatment to the nature of the migraine attack being treated. Although an antiemetic may not be
necessary if the triptan works well, antiemetics can be a useful addition to the triptan in patients
with significant nausea or vomiting. Prochlorperazine has more extrapyramidal side effects than
metoclopramide, but the suppository formulation can be very helpful, particularly if patients vomit
with some of their attacks.
rate and a low headache recurrence rate.

Four triptans contain a sulfonyl group
or a sulfonamide moiety (sumatriptan,
almotriptan, eletriptan, and naratriptan).
Although patients with a sulfonamide allergy usually tolerate these triptans well,
if previous allergic reactions to sulfonamides have been severe, a sulfur-free
triptan can be chosen (eg, rizatriptan,
frovatriptan, or zolmitriptan). For a summary of the triptan strategy, see Table 1-3.
Much of the data on which triptan
comparisons are based derive from metaanalyses of studies in which patients were
treated when the pain was moderate or
severe in intensity, but fewer data exist
on how the various triptans compare
when they are taken early in the migraine
attack. When triptans are taken earlier
while pain is still mild, headache relief and
pain-free response rates are higher23 and
headache recurrence rates may also be
lower. Taking a triptan early while pain
is still mild is advantageous for most
patients if past experience has shown
that such attacks are likely to progress

to moderate or severe intensity and
respond less well when a triptan is taken
later in the attack. Caution must be exercised in patients with relatively frequent
migraine attacks, as medication overuse
needs to be avoided. If patients are at
risk for medication-overuse headache,
preventive medications and behavioral
interventions should be considered.
Headache recurrence within 24 hours
of initial successful treatment is usually
best treated with a second dose of the
same triptan that was taken initially. Several options are available to reduce the
recurrence rate in patients prone to headache recurrence after triptan treatment
(Case 1-2). Naproxen sodium 500 mg to
550 mg can be added to the triptan, as
headache recurrence after sumatriptan
has been shown to be reduced when
naproxen is added to the sumatriptan.11
Alternatively, another triptan with a relatively low recurrence rate (eg, eletriptan,
frovatriptan, or naratriptan) can be tried,
961
a,b,c
TABLE 1-3 Triptan Strategy for Moderate and Severe Attacks
Medication
Usual and Maximum

Daily Dosed
Almotriptan tabletse
12.5 mg
Maximum 25 mg/d
Eletriptan tablets
40 mg
Maximum 80 mg/d
Frovatriptan tablet
2.5 mg
Maximum 5 mg/d
Naratriptan tablets
2.5 mg
Maximum 5 mg/d
Rizatriptan tabletse,f
10 mg
Maximum 20 mg/d
e,f
Rizatriptan wafers (orally dispersible tablets)
10 mg
Maximum 20 mg/d
Sumatriptan tablets
100 mg (50 mg also used)

Maximum 200 mg/d
e
20 mg
Sumatriptan intranasal
Maximum 40 mg/d
Sumatriptan injection
4Y6 mg
Maximum 12 mg/d
Zolmitriptan tablets
2.5Y5 mg
Maximum 10 mg/d
Zolmitriptan wafers (orally dispersible tablets)
2.5 mg
Maximum 10 mg/d
Zolmitriptan intranasal
5 mg
Maximum 10 mg/d
Selected side effects of triptans include flushing, hot or warm sensation, paresthesia, and chest or
jaw discomfort or tightness.
Limit the use of triptans to fewer than 10 days per month to avoid medication-overuse headache.
c
Triptans are contraindicated in cerebrovascular, cardiovascular, and peripheral vascular disorders;
in uncontrolled hypertension and ischemic bowel disease; and in concomitant use within 24 hours
of ergot-containing medications.
d
Dosages are for adults. For acute migraine treatment, only one dose is usually recommended, followed
by a second dose (2 hours or more after the first dose) if the headache reoccurs after initial relief.
e
Avoid the use of almotriptan, rizatriptan, sumatriptan, and zolmitriptan with monamine oxidase
inhibitors and within 2 weeks after discontinuation of monamine oxidase inhibitors.
f
For rizatriptan, reduce the dose to 5 mg (maximum 10 mg per day) if the patient is also on propranolol.
b
962
August 2015
KEY POINTS
Case 1-2
h Headache recurrence
A 28-year-old man with a long history of severe migraine attacks, which

increased rapidly in intensity after onset, was concerned because, although
his headaches responded well to oral sumatriptan 100 mg taken early in
the attack, his headaches usually recurred after 8 to 12 hours. He took
acetaminophen with codeine for these recurrent headaches, but obtained
only partial relief from this approach.
Several therapeutic options were discussed with him, and it was decided
to switch his triptan to eletriptan 40 mg as this triptan has a longer half-life
than sumatriptan, and evidence exists that it has a lower headache recurrence
rate than sumatriptan. He tried this strategy, but he continued to experience
frequent headache recurrence with the eletriptan and often needed to take
a second dose later in the day for the recurrent headache. At this point, he was
advised to take naproxen sodium 550 mg simultaneously with the eletriptan
when treating his initial migraine attack.
Comment. Headache recurrence after triptan treatment is not
uncommon. A second dose of the triptan is very useful in treating headache
recurrence, in contrast to headache persistence (no or little relief after
initial triptan treatment) where a second triptan dose is of questionable
benefit. The triptans appear to differ in their recurrence rates, but this is
hard to assess as a headache can only recur if it responds to the initial triptan
treatment. Frovatriptan, which has the longest half-life of all the triptans, has
a low recurrence rate and can be useful in patients with headache recurrence.
However, frovatriptan has lower response rates at early time points after
dosing as compared to eletriptan and therefore was not considered for this
patient. Adding a nonsteroidal anti-inflammatory drug can also improve
responsiveness to triptans, and naproxen sodium, with its long half-life,
appears especially well suited for reducing headache recurrence. Treatment
with the triptan early in the attack also has the potential
to reduce headache recurrence.
but frovatriptan and naratriptan have a

slower onset of action and higher numbers needed to treat for pain free at
2 hours (8.5 for frovatriptan and 8.2 for
naratriptan). DHE also has a long halflife and a low headache recurrence rate.
Headache persistence is said to occur when the initial triptan dose fails to
provide a clinically meaningful response.
In contrast to headache recurrence, clinical trials suggest that a second triptan
dose is no more helpful than placebo
under these circumstances.24 Some patients do indicate that a second triptan
dose is helpful to them, but this is difficult
to interpret given the high placebo response to medication taken for headache persistence in clinical trials, perhaps
can be minimized by
treatment early in the
migraine attack,
choosing a triptan with a
relatively longer half-life
(eg, eletriptan, frovatriptan),
combining a long
half-life nonsteroidal
anti-inflammatory
drug with the triptan
(eg, naproxen sodium), or
using dihydroergotamine.
h For headache recurrence

after initial relief, a
second triptan dose is
often the best treatment
option. In contrast, for
headache persistence
(no response to the initial
triptan dose), another
rescue medication is
usually the best option.
because the initial triptan dose is still

active. It may be prudent to use another
rescue medication if the initial triptan
dose fails.
Although early treatment is recommended for patients with migraine without aura, data from several small clinical
trials do not support triptan treatment
during the migraine aura, at least for
subcutaneous sumatriptan and oral
eletriptan. As a result, it has been recommended that patients experiencing migraine with aura take their triptan at the
onset of the pain phase of the migraine
attack. Nevertheless, some patients do
report success with triptan treatment during the aura.25 Triptan treatment during
typical aura appears to be safe,26 and if
963

KEY POINT
h Triptan effectiveness
can be enhanced by
taking the triptan early
in the attack and, if
necessary, by taking
a nonsteroidal
anti-inflammatory drug
(eg, naproxen sodium)
with the triptan.
patients report success with treatment

during the aura, there is no need to
discourage this strategy.
Triptans taken alone will often relieve
migraine-related nausea satisfactorily,
but metoclopramide or domperidone
can be added to any triptan if necessary.
The prokinetic effect of metoclopramide
may also promote triptan absorption.
In one study it was found that patients
who did not receive adequate relief
from sumatriptan 50 mg alone had better headache relief with the addition
of metoclopramide.27
Refractory Migraine Strategies
Several options are available for patients
who do not respond adequately to either
NSAIDs or triptans (Case 1-3). Clinical
trials have clearly shown that when naproxen sodium is combined with sumatriptan, migraine attack response rates
are better than with either drug alone.11
Despite a lack of evidence, extending
these observations to other triptan/
NSAID combinations appears reasonable. Most triptans have a relatively short

half-life, and, because of its long half-life,
naproxen sodium may be particularly
well suited for triptan/NSAID combination therapy as compared to other
NSAIDs, particularly in reducing the rate
of migraine recurrence. If the intent is to
improve headache relief at 2 hours, a
faster-acting NSAID, such as ibuprofen
or diclofenac, might be more effective.
A recent clinical trial that compared a
combination of frovatriptan 2.5 mg (a
long half-life triptan) to a combination
of frovatriptan and a fast-acting, short
half-life NSAID (dexketoprofen) supported this concept in that the combination resulted in higher pain-free
rates at 2 hours than frovatriptan alone
(51% versus 29%).28
For patients who usually, but not
always, respond to a triptan/NSAID combination, it may be helpful to provide a rescue medication to use when their usual
medication fails. However, the options
Case 1-3
A 44-year-old woman reported that her sumatriptan 100 mg tablets provided
only incomplete relief from her migraine attacks. Early treatment of her
attacks reduced their severity, but she was still left with a mild headache, which
remained troublesome for another 12 hours. She had also tried rizatriptan,
eletriptan, almotriptan, and frovatriptan in the past and felt that, of all of the
triptans she had tried, sumatriptan provided her with the best overall relief.
She was advised to take naproxen sodium 550 mg simultaneously with
her sumatriptan to enhance the efficacy of her acute treatment.
Comment. Adding naproxen to sumatriptan has been shown to
improve efficacy. Many clinicians will use naproxen sodium with other
triptans based on these findings or use triptans with other nonsteroidal
anti-inflammatory drugs (NSAIDS), which seems reasonable, although the
sumatriptan/naproxen combination is the only one that has been well
studied. Although there have not been randomized controlled trials to
address all these issues, if an NSAID is being added in a patient with
migraine attacks that build up rapidly and more rapid complete relief is
desired, use of a rapidly acting NSAID such as ibuprofen or diclofenac may
be most useful. If headache recurrence or long-lasting lower level pain is
being addressed, then naproxen with its long half-life may be a more
reasonable choice. Naproxen sodium is preferred over other forms of
naproxen because of faster absorption.
964
August 2015
are limited if vomiting reduces the usefulness of oral medications. If a triptan

has already been used, further vasoconstrictors need to be avoided. Dopamine
antagonists are options, including prochlorperazine orally (10 mg, with up to
four doses in 24 hours) or by suppository (10 mg to 25 mg, maximum daily
dose 50 mg), and chlorpromazine orally
(10 mg to 50 mg, with up to four doses
in 24 hours) or intramuscularly (25 mg
to 50 mg, with up to four doses in
24 hours). Both are powerful antiemetics,
and the sedation they provide may also
be helpful.
NSAIDs for rescue may be problematic
if the patient has already taken naproxen
sodium. Ketorolac 60 mg by IM selfinjection can be used safely at home if
patients are adequately trained.29 Indomethacin orally (50 mg to 75 mg) or by
suppository (50 mg to 100 mg) can be
used, but evidence for efficacy is limited.
A short course of prednisone (60 mg
on the first day with a rapid taper over
3 or 4 days) or dexamethasone (8 mg on
the first day with a rapid taper over 3 or
4 days) can be considered for occasional
use. Dexamethasone 4 mg plus rizatriptan
10 mg in a single-dose study resulted in
a higher proportion of patients achieving
a 24-hour sustained pain-free end point
(50.7%) than rizatriptan alone (32.2%) in
a menstrually related migraine study.30
Therefore, steroids may be of some use
in patients in whom triptan therapy
occasionally fails, but the evidence is
very limited.
Combination analgesics containing
isometheptene have been widely used
in the past for migraine, although little
evidence exists for the effectiveness of
isometheptene alone. Isometheptene is
a sympathomimetic amine that is thought
to exert its effects through vasoconstriction and is often combined with acetaminophen and caffeine. Physicians should be
aware that in some combination analgeContinuum (Minneap Minn) 2015;21(4):953972
sics, isometheptene is combined with

dichloralphenazone. Dichloralphenazone
is a mixture of antipyrine (an NSAID) and
chloral hydrate (a hypnotic) and may not
be an ideal medication for the modern
treatment of migraine. A recent review
of combination analgesics and migraine
treatment summarized the evidence for
the use of isometheptene combination
analgesics for migraine, but did not provide conclusions with regard to the place
of these treatments in migraine therapy.31
Combination analgesics with codeine
or tramadol are additional options for
rescue mediations when triptans occasionally fail or for patients who do not
respond to triptans. Opiates should not
be used routinely in migraine therapy,
but occasional use when necessary in
selected patients is a potential option.
There is concern that opioid use can
lead to receptor changes, which may
make patients with migraine less responsive to other drugs, and opioid use
may escalate over time and lead to
medication-overuse headache. Intranasal butorphanol is best avoided because
of risk of addiction and dependence, although it may be useful in selected cases
as it can be used even if patients are
vomiting. Frequency of use of all opioids
should be carefully monitored. Combination analgesics with barbiturates (eg,
butalbital) should be avoided and used
only under very exceptional circumstances, if at all, as barbiturate-containing
combination analgesics are a potent
cause of medication-overuse headache.
A large, randomized, double-blind crossover trial demonstrated that a sumatriptan/
naproxen combination was superior to a
butalbital, acetaminophen, caffeine combination tablet on most end points.32
Some patients who do not respond
well to triptans will respond to ergotamine
or DHE. DHE is the preferred drug, and
can be given by nasal spray (one 0.5-mg
spray in each nostril, repeated after 15
965

KEY POINTS
h For patients who do not

respond to nonsteroidal
anti-inflammatory
drugs or the triptans,
dihydroergotamine,
metoclopramide,
prochlorperazine, and a
number of combination
analgesics (with and
without tramadol or
codeine) are potential
therapeutic options.
h Medication use should be

minimized as much as
possible during pregnancy,
but acetaminophen,
acetaminophen with
codeine, and
metoclopramide are
considered safe acute
treatments for migraine.
Available data indicate
sumatriptan is also
relatively safe and could
be considered for use
during pregnancy
where warranted.
to 30 minutes [maximum dose 4 mg per

day]) or by subcutaneous or IM selfinjection (usual dose 1 mg, preceded by
metoclopramide 10 mg orally [maximum
daily dose for parenteral DHE 3 mg
per day]). Nausea is a common side effect. If leg cramps or coldness and tingling of the hands and feet occur, DHE
should be reduced or discontinued. A
new orally inhaled formulation of DHE
has shown promise of good efficacy
(28.4% pain free at 2 hours) but is not
yet available.33 DHE is not available in
oral formulations.
Ergotamine tartrate is not recommended for routine use, and triptans
are a better option for most patients.
Ergotamine tartrate may be helpful in
patients with prolonged attacks who do
not respond well to the triptans. Patients
need to find a subnauseating dose that
is effective for their migraine attacks
(usual dosage range is 0.5 mg to 2 mg).34
Refractory migraine strategies are summarized in Table 1-4 and Table 1-5.
Strategies for Patients With
Contraindications to
Vasoconstricting Drugs
Acute treatment options for patients
with contraindications to vasoconstricting drugs (Table 1-6) include the NSAIDs
and most of the rescue medications
previously discussed (eg, dopamine antagonists, ketorolac injections, indomethacin, steroids, and combination
analgesics with codeine or tramadol). If
acute medications are used frequently,
however, it should be kept in mind that
many NSAIDs have been associated with
an increased risk of cardiovascular events.
Naproxen sodium may be an exception
and may be the preferred NSAID in patients with cardiovascular disease.35
Nonopioid combination analgesics
may also be helpful. Combination analgesics containing acetaminophen, ASA,
and caffeine have been found superior
to the combination of acetaminophen
966
and ASA without caffeine, to ASA alone,

and to acetaminophen alone.36 Combination analgesics without opiates may be
helpful when triptans are contraindicated
or ineffective. A combination of acetaminophen 400 mg per day, ASA 500 mg
per day, and caffeine 100 mg given as a
single dose was found to be effective
even in patients with severe headache
attacks compared to placebo.37 Combination analgesics containing isometheptene are considered contraindicated in
patients with vascular disease because
of its vasoconstrictor properties.
Pharmacologic prophylactic therapy
and behavioral treatment approaches
should be maximized for all patients
where acute pharmacologic therapy is
problematic or ineffective.
MIGRAINE DURING PREGNANCY
No drug has been proven to be safe during
pregnancy, so drug use should be avoided
as much as possible and behavioral approaches maximized. Acetaminophen
and metoclopramide are considered safe,
while acetaminophen with codeine is
also considered relatively safe, although
caution should be observed toward the
end of pregnancy because of potential
withdrawal symptoms in the neonate and
because of a slight association with acute
cesarean delivery and postpartum hemorrhage.38 Other opioids may also cause
harmful effects on the fetus or neonate
without causing malformations.
ASA should be avoided in pregnancy.
Other NSAIDs are preferable because of
less prolonged effects on platelet function. All NSAIDs should be avoided after
the 32nd week of gestation because of
effects on the ductus arteriosus, and it
may be best to avoid NSAIDs in the first
trimester because of a possible increased
risk of spontaneous abortion, although in
a recent historical cohort study, exposure
to NSAIDs during pregnancy was not
an independent risk factor for spontaneous abortion.39
August 2015
TABLE 1-4 Refractory Migraine Strategies

Usual and Maximum
Daily Dosea
Medication
Sumatriptan and
naproxen sodium
taken simultaneously
Sumatriptan 100 mg,

naproxen sodium
500Y550 mg (other
doses are also used in
combination tablets)
Selected Side Effects
Comments
See Table 1-2 and Table 1-3
The combination is more

effective than either
drug alone
See Table 1-2 and Table 1-3
Maximum two doses

Other triptans and
other nonsteroidal
anti-inflammatory
drug combinations
See Table 1-2 and

Table 1-3 for
individual drugs
See Table 1-2 for

individual drugs
Randomized clinical trials

not available for most
combinations
Dihydroergotamine
intranasal
0.5 mg in each nostril,

repeat dose in 15 minutes;
may repeat four-spray
sequence in 6 hours
if necessary
Nausea, vomiting, muscle

cramps, paresthesia, and
other side effects related
to vasoconstriction; rhinitis
and taste disturbance
Contraindicated in
vascular disease
Maximum 4 mg/d
Limit use to under 10 days a

month for most patients,
but relationship to
medication-overuse
headache uncertain.
Avoid dihydroergotamine
with CYP3A inhibitors
(eg, clarithromycin,
ketoconazole, ritonavir)
Dihydroergotamine
subcutaneous or
IM injection
0.5Y1 mg, dose may

be repeated in 3 hours
if necessary
Maximum 3 mg/d

to vasoconstriction
Contraindicated in
vascular disease
Limit use to under 10 days a
month for most patients,
but relationship to
medication-overuse
headache uncertain.
Avoid dihydroergotamine
with CYP3A inhibitors
(eg, clarithromycin,
ketoconazole, ritonavir)
Ergotamine tartrate
sublingual tablets
0.5Y2 mg
Maximum 6 mg/d

to vasoconstriction
Contraindicated in
vascular disease
Limit use to fewer than
10 days a month to avoid
medication-overuse headache
IM = intramuscular.
a
Dosages are for adults.
Although ergotamines must be avoided

owing to uterotonic effects, triptans appear much safer during pregnancy. A
large observational study found no asContinuum (Minneap Minn) 2015;21(4):953972
sociation between sumatriptan use in

the first trimester and fetal malformations or adverse pregnancy outcomes.
Sumatriptan use in the second and
967
a
TABLE 1-5 Refractory Migraine Strategies: Rescue Medications
Medication
Usual Doseb
Comments
Prochlorperazine
tablets
10 mg
Extrapyramidal symptoms,
drowsiness
Dopamine antagonist
Prochlorperazine
suppositories
10Y25 mg
drowsiness
Dopamine antagonist, helpful

if severe nausea or vomiting
Chlorpromazine
tablets
10Y50 mg
drowsiness
Limited evidence for efficacy
Ketorolac by IM
self-injection
60 mg
Gastrointestinal disturbance,
renal toxicity, injection site pain
Patients must be
adequately trained
Indomethacin
tablets
50Y75 mg
Indomethacin
suppositories
50Y100 mg
Prednisone tablets
60 mg on the first day,

with rapid taper over
several days
Insomnia, behavioral change,

other steroid side effects
Only for occasional use for

prolonged attacks
Dexamethasone
tablets
8 mg on the first day,

with rapid taper over
several days
Insomnia, behavioral change,

other steroid side effects
Only for occasional use for

prolonged attacks
Maximum 40 mg/d
Maximum 50 mg/d
Maximum 200 mg/d

Maximum 120 mg/d
Maximum 200 mg/d

Maximum 200 mg/d
Combination analgesics Individualized dosing

with isometheptene
See nonsteroidal anti-inflammatory Limited evidence

drugs in Table 1-2
for efficacy
See nonsteroidal anti-inflammatory Limited evidence for efficacy
drugs in Table 1-2
Depends on tablet ingredients Isometheptene is a

vasoconstrictor; avoid in
vascular disease
Combination
analgesics with
tramadol or codeine
Individualized dosing
Drowsiness, constipation
Monitor frequency of use

as a risk of medication
overuse-headache exists
Butorphanol
intranasal
1 mg (1 spray) in one
nostril, repeat once in 60
to 90 minutes if necessary;
repeat two-dose sequence
in 6 hours if necessary
CNS depression, sedation,

respiratory depression,
dependence, abuse, possible
addiction
Use only in exceptional

circumstances and limit
use to fewer than 8 days
per month to avoid
Butalbital-containing Avoid if possible

combination analgesics
Strong opiates (eg,
Avoid if possible
morphine, oxycodone)
IM = intramuscular; CNS = central nervous system.
a
Rescue medications to be used when primary medication fails; consider whether related drugs have been used in past 24 hours.
With migraine, most rescue medications are meant for occasional use, and some are potential options for primary medications
in patients who are unresponsive to nonsteroidal anti-inflammatory drugs and vasoconstrictors.
b
Dosages are for adults.
third trimester was associated with

atonic uterus and blood loss of greater
than 500 mL during labor and delivery.40
Much fewer data exist with regard to the
other triptans. Although still controver-
968
sial, sumatriptan may be an option for

pregnant women with difficult migraine
that often renders them incapable of
carrying out tasks of daily living or results
in dehydration.
August 2015
a
TABLE 1-6 Strategies for Patients With Contraindications to Vasoconstricting Drugs
Medication
Usual Dose
Comments
Acetylsalicylic acid,
acetaminophen, and
caffeine combination
analgesics
Individualized
dosing
Gastric irritation (acetylsalicylic

acid), liver toxicity at high
doses (acetaminophen),
insomnia (caffeine)
Combinations may be more

effective than individual
drugs alone
Combination analgesics
with tramadol or
codeine
Individualized
dosing
Drowsiness, constipation,
others according to ingredients
Limit use to fewer than

10 days per month to avoid
Nonsteroidal anti-inflammatory drugs including indomethacin, dopamine antagonists, and many of the rescue medications discussed in
the refractory migraine strategies are also options for patients with contraindications to vasoconstricting drugs. Please see previous tables in
this article for dosing and side effects.
Lidocaine is safe in pregnancy, so occipital nerve blocks can be considered.

Prochlorperazine and other phenothiazines are not considered to be teratogenic, but their use near term may be
associated with extrapyramidal effects in
the newborn. Short courses of steroids
given after 10 weeks gestation appear
not to pose a risk to the fetus.41
MIGRAINE DURING LACTATION
Acetaminophen is considered safe during breast-feeding. Among the NSAIDs,
ibuprofen is preferred. Occasional use of
diclofenac and ketorolac is considered
compatible with breast-feeding, but ASA
in analgesic doses should be avoided.
The amount of infant exposure from
maternal use of sumatriptan appears to
be small, and sumatriptan use is considered compatible with breast-feeding.42
Metoclopramide, domperidone, prochlorperazine, and dimenhydrinate are all
considered safe.43
If an opioid must be used, morphine is
the opioid of choice, but the milk should
be discarded if the mother experiences
significant sedation. Caution should be
exercised, particularly with premature
infants and infants under 1 month of age.
Because of variable maternal metabolism,
codeine should be avoided as exposure
of the infant to morphine (a metabolite of
codeine) may be much higher than expected if the mother is a fast metabolizer
of codeine (5% to 40% of individuals,
depending on ethnic background).44
CONCLUSION
Many drugs have shown efficacy for
acute migraine treatment in doubleblind, randomized controlled trials. However, choosing the best medication for
a specific patient remains a complex
task and requires careful consideration
of the patients clinical features and preferences. Adequate patient education
and an organized approach to medication choice is important.
Patients may have more options for
acute migraine treatment in the future,
including single-pulse transcranial magnetic stimulation, which has shown promise for acute treatment of migraine with
aura,45 and noninvasive vagal nerve stimulation, which is under investigation.46
New delivery systems for sumatriptan,
which may eventually be applied to other
drugs as well, are either becoming available or are under active investigation
and include a needle-free injection system,47 transdermal drug delivery systems,48
and breath-powered devices for better
drug delivery through the nasal mucosa.49
Research in these areas and others bodes
well for the treatment of acute migraine
969
attacks in the near future. An updated

assessment of the evidence for the available pharmacologic therapies for acute
migraine treatment has also recently
been published.50
6. Katsarava Z, Schneeweiss S, Kurth T, et al.

Incidence and predictors for chronicity of
headache in patients with episodic migraine.
Neurology 2004;62(5):788Y790. doi:10.1212/
01.WNL.0000113747.18760.D2.
USEFUL WEBSITES
Scottish Intercollegiate Guidelines
Network (SIGN). SIGN provides a
clinical guideline for the diagnosis and
management of headache in adults,
including assessment tools and treatment recommendations.
www.sign.ac.uk/pdf/sign107.pdf
7. Lipton RB, Stewart WF, Stone AM, et al. Disability

in Strategies of Care Study group. Stratified
care vs step care strategies for migraine: the
Disability in Strategies of Care (DISC) Study:
a randomized trial. JAMA 2000;284(20):
2599Y2605. doi:10.1001/jama.284.20.2599.
Toward Optimized Practice (TOP).

TOP provides a variety of resources
for headache management, including
guidelines and assessment tools.
9. Treatment of migraine attacks with sumatriptan.

The Subcutaneous Sumatriptan International
Study Group. N Engl J Med 1991;325(5):316Y321.
www.topalbertadoctors.org/cpgs/10065
Motherisk, published by The Hospital
for Sick Children, University of Toronto.
Motherisk provides links to published
studies on the safety or risk of specific
drugs during pregnancy.
www.motherisk.org/women/drugs.jsp
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