Migraine headache treatment

Migraine Headache Treatment & Management
Author: Jasvinder Chawla, MD, MBA; Chief Editor: Helmi L Lutsep, MD more...

Updated: Jun 22, 2016
Approach Considerations
Migraine treatment involves acute (abortive) and preventive (prophylactic) therapy.
Patients with frequent attacks usually require both. Measures directed toward
reducing migraine triggers are also generally advisable.
Acute treatment aims to reverse, or at least stop, the progression of a headache that
has started. Preventive treatment, which is given even in the absence of a
headache, aims to reduce the frequency and severity of the migraine attack, make
acute attacks more responsive to abortive therapy, and perhaps also improve the
patient's quality of life. An overview of migraine treatment is shown in the image
below.
Overview of migraine treatment. Five steps.
Migraineurs should be screened for cardiovascular risk factors, which, if present,
should be aggressively treated. Migraineurs with aura should also be counseled on
the increased risk of stroke with smoking and oral contraceptive use.
A neurologist, neuroophthalmologist, and/or neurosurgeon should be consulted as
deemed clinically appropriate for the treatment of patients with migraine.
Emergency Department Considerations
Emergency medical services personnel should transport patients in a way that
minimizes visual and auditory stimulation. Once in the emergency department (ED),
most patients should not receive opiate analgesics until a thorough neurologic
examination can be completed by the responsible physician.
While the emergency physician must be able to identify patients with serious

headache etiology, note that more than 90% of patients who present to the ED
because of headache have migraine, tension, or mixedtype benign headache.
Therefore, providing symptomatic relief should be a priority. Rest in a darkened,
quiet room is helpful. Some patients find cool compresses to painful areas helpful.
Migrainespecific medications and analgesia are key elements of ED care. Although
narcotics remain the most frequently administered medication for patients with
migraine and for ED patients with headache, evidence suggests that they are
potentially ineffective, and their use may lead to more prolonged ED stays.[80, 81]
Friedman et al found that nearly three quarters of ED patients with migraine or other
primary headache reported headache recurrence within 48 hours of ED discharge;
in this study, naproxen 500 mg and oral sumatriptan 100 mg provided comparable
relief of postED recurrent migraine.[82]
Hospital admission for migraine may be indicated for the following:
Treatment of severe nausea, vomiting, and subsequent dehydration
Treatment of severe, refractory migraine pain (ie, status migrainosus)
Detoxification from overuse of combination analgesics, ergots, or opioids
Reduction of Migraine Triggers
Patients should avoid factors that precipitate a migraine attack (eg, lack of sleep,
fatigue, stress, certain foods, use of vasodilators). Encourage patients to use a daily
diary to document the headaches. This is an effective and inexpensive tool to follow
the course of the disease.
Patients may need to discontinue any medications that exacerbate their headaches.
If an oral contraceptive is suspected to be a trigger, the patient may be advised to
modify, change, or discontinue its use for a trial period.[83] Similarly, when hormone
replacement therapy is a suspected trigger, patients should reduce dosages, if
possible. If headaches persist, consider discontinuing hormone therapy.
Nonpharmacologic Therapy
Biofeedback, cognitivebehavioral therapy, and relaxation therapy are frequently
effective against migraine headaches and may be used adjunctively with
pharmacologic treatments. Occipital nerve stimulators may be helpful in patients
whose headaches are refractory to other forms of treatment.
In December 2013, the FDA approved the Cerena Transcranial Magnetic Stimulator
(Cerena TMS), the first device to relieve pain caused by migraine headache with
aura for use in patients aged 18 years and older. Users hold the device with both
hands to the back of the head and press a button to release a pulse of magnetic
energy that stimulates the occipital cortex. The recommended daily usage of the
device is not to exceed one treatment in 24 hours.[84, 85]
Approval for the Cerena TMS was based on a randomized study of 201 patients with

moderate to strong migraine headaches, in which 39% of the patients using the
device were painfree 2 hours following its use, relative to 22% of control patients
(therapeutic gain: 17%).[86, 87] At 24 hours, nearly 34% of patients treated with the
device were painfree, compared with 10% of the control group.
Contraindications and precautions regarding the use of the Cerena TMS include the
following[84, 85] :
Do not use for patients with any metal in the head, neck, or upper body that is
attracted by a magnet
Do not use for patients with an active implanted medical device (eg,
pacemaker, deep brain stimulator)
Do not use for patients with suspected/diagnosed epilepsy or who have a
personal or family history of seizures
Trials of nonpharmacologic management have produced average reduction in
migraines of 4050%, closely paralleling results obtained in trials of preventive
drugs; however, the evidence base for nonpharmacologic and pharmacologic
prevention remains limited. A 16month randomized, placebocontrolled trial by
Holryod et al found that the combination of betablocker therapy and behavioral
management improved outcomes in patients with frequent migraines, while neither
intervention was effective by itself.[88]
Abortive Therapy
Numerous abortive medications are used for migraine. The choice for an individual
patient depends on the severity of the attacks, associated symptoms such as
nausea and vomiting, comorbid problems, and the patient's treatment response. A
stratified approach based on the patient's therapeutic needs has been advanced
(see Table 1, below), as has a steppedcare approach.
Table 1. Abortive Medication Stratification by Headache Severity (Open Table in a
new window)
Moderate Severe Extremely Severe
NSAIDs Naratriptan DHE (IV)
Isometheptene Rizatriptan Opioids
Ergotamine Sumatriptan (SC,NS) Dopamine antagonists
Naratriptan Zolmitriptan
Rizatriptan Almotriptan
Sumatriptan Frovatriptan
Zolmitriptan Eletriptan
Almotriptan DHE (NS/IM)
Frovatriptan Ergotamine

Eletriptan Dopamine antagonists
Dopamine antagonists
DHE=Dihydroergotamine; NSAIDs=nonsteroidal antiinflammatory drugs
Simple analgesics alone or in combination with other compounds have provided
relief for mild to moderately severe headaches and sometimes even for severe
headaches.[89] Acute treatment is most effective when given within 15 minutes of
pain onset and when pain is mild.[90]
Analgesics used in migraine include acetaminophen, NSAIDs, and narcotic
analgesics (eg, oxycodone, morphine sulfate). Propoxyphene (Darvon) was formerly
used; however, propoxyphene products were withdrawn from the United States
market in 2010, because this agent can cause prolonged PR interval, widened QRS
complex, and prolonged QT interval at therapeutic doses. For more information, see
MedWatch safety information, from the US Food and Drug Administration (FDA).
For more severe pain, 5hydroxytryptamine–1 (5HT1) agonists (triptans) and/or
opioid analgesics are used, either alone or in combination with dopamine
antagonists (eg, prochlorperazine [Compazine]). The use of abortive medications
must be limited to 23 days a week to prevent development of a rebound headache
phenomenon.
Intravenous metoclopramide is recognized as an effective therapy for acute
migraine, but the optimal dosing has not been established. A study by Friedman et
al determined that 20 or 40 mg of metoclopramide is no better in the treatment of
acute migraine than 10 mg of the drug.[91]
A systematic review by Taggart et al found that ketorolac is an effective alternative
agent for the relief of acute migraine headache in the ED. Ketorolac provides pain
relief similar to that with meperidine (with less potential for addiction) and is more
effective than sumatriptan; however, it may not be as effective as
metoclopramide/phenothiazine agents. Sideeffect profiles were similar with
ketorolac and these other agents.[92]
Triptans and ergot alkaloids
The 2 categories of migrainespecific oral medications are triptans and ergot
alkaloids. The specific ergot alkaloids include ergotamine and dihydroergotamine
(DHE).[93] The specific triptans include the following[94] :
Sumatriptan
Rizatriptan
Zolmitriptan
Naratriptan
Almotriptan
Eletriptan
Frovatriptan

Although the triptans share a common mechanism of action, they differ in the
available routes of administration, onset of action, and duration of action. Routes of
administration include oral, intranasal, subcutaneous, and intramuscular.
Transdermal patches have proved effective for the delivery of sumatriptan, and one
such product has received FDA approval.[95] The sumatriptan iontophoretic
transdermal system (Zecuity, NuPathe Inc) was approved by the FDA in January
2013 for the acute treatment of migraine with or without aura in adults. The single
use patch also treats migrainerelated nausea. In phase 3 trials involving 800
patients, the patches safely and effectively relieved migraine pain, migrainerelated
nausea, sonophobia, and photophobia within 2 hours of activation.[95]
The FDA approved a lowdose intranasal sumatriptan powder for migraine in
January 2016. The product consists of 22 mg of sumatriptan powder and is the first
breathpowered intranasal medication delivery system to treat migraines. Approval
was based on data from phase 2 and phase 3 trials, reference data on the use of
sumatriptan, and safety data from more than 300 patients.[96, 97]
All the triptans are most effective when taken early during a migraine and all may be
repeated in 2 hours as needed, with a maximum of 2 doses daily. While different
formulations of a specific triptan may be used in the same 24hour period, only 1
triptan may be used during this time frame.
The longeracting triptans (eg, frovatriptan, naratriptan) may be used continuously
for several days (miniprophylaxis) to treat menstrual migraine. Triptans should not
be used more than 3 days weekly, to avoid transformed migraine and medication
overuse headache.
The effectiveness and tolerability of triptans varies among patients. Lack of response
or side effects experienced with one triptan does not predict the response to another.
The safety of triptans is well established, and the risk of de novo coronary
vasospasm from triptan use is exceedingly rare. However, triptans should not be
taken by patients with known or suspected coronary artery disease, as they may
increase risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular
events.
The dose of rizatriptan must be reduced to 5 mg in patients taking propranolol.
Sumatriptan, zolmitriptan, and rizatriptan are primarily metabolized by monoamine
oxidase (MAO) and should be avoided in patients taking MAOA inhibitors.
The first combination product of a triptan and an NSAID, Treximet, was approved by
the FDA in 2008. Treximet contains sumatriptan and naproxen sodium. In 2
randomized, doubleblind, multicenter, parallelgroup trials, a significantly greater
percentage of patients remained pain free for 24 hours postdose after a single dose
of Treximet (25% and 23%) than after use of placebo (8% and 7%) or either
sumatriptan (16% and 14%) or naproxen sodium (10%) alone.[98]
Patients with severe headaches need subcutaneous, intravenous, or oral
formulations of an ergot alkaloid or triptan. Do not administer vasoconstrictors, such
as ergots or triptans, to patients with known complicated migraine; treat their acute

attacks with one of the other available agents, such as NSAIDs or prochlorperazine.
Treatment of nausea and vomiting
Antiemetics (eg, chlorperazine, promethazine) are used to treat the emesis
associated with acute migraine attacks. Patients with severe nausea and vomiting at
the onset of an attack may respond best to intravenous prochlorperazine. These
patients may be dehydrated, and adequate hydration is necessary.
Antiemetics are commonly combined with diphenhydramine to minimize the risk of
akathisia. This combination of drugs has been found to be superior to subcutaneous
sumatriptan when given intravenously in emergency patients.[99]
Prophylactic Therapy
The following may be considered indications for prophylactic migraine therapy:
Frequency of migraine attacks is greater than 2 per month
Duration of individual attacks is longer than 24 hours
The headaches cause major disruptions in the patient’s lifestyle, with
significant disability that lasts 3 or more days
Abortive therapy fails or is overused
Symptomatic medications are contraindicated or ineffective
Use of abortive medications more than twice a week
Migraine variants such as hemiplegic migraine or rare headache attacks
producing profound disruption or risk of permanent neurologic injury [5]
The goals of preventive therapy are as follows:
Reduce attack frequency, severity, and/or duration
Improve responsiveness to acute attacks
Reduce disability
Currently, the major prophylactic medications for migraine work via one of the
following mechanisms:
5HT2 antagonism Methysergide
Regulation of voltagegated ion channels Calcium channel blockers
Modulation of central neurotransmitters Beta blockers, tricyclic
antidepressants
Enhancing gammaaminobutyric acidergic (GABAergic) inhibition Valproic
acid, gabapentin
Another notable mechanism is alteration of neuronal oxidative metabolism by
riboflavin and reduction of neuronal hyperexcitability by magnesium replacement.
As with abortive medications, the selection of a preventive medication must take into
consideration comorbid conditions and the sideeffect profile (see Tables 2 and 3,
below). Most preventive medications have modest efficacies and have therapeutic

gains of less than 50% when compared with placebo. The latency between initiation
of therapy and onset of positive treatment response can be quite prolonged.
Furthermore, the scientific basis for using most of these medications is wanting.
Table 2. Preventive Drugs for Migraine (Open Table in a new window)
First line
High efficacy
Beta blockers
Tricyclic antidepressants
Divalproex
Topiramate
Low efficacy Verapamil
Second line

High efficacy
Methysergide
Flunarizine
MAOIs

Unproven efficacy
Cyproheptadine
Gabapentin
MAOIs = monoamine oxidase inhibitors
Table 3. Preventive Medication for Comorbid Conditions (Open Table in a new
window)

Comorbid Condition Medication
Hypertension Beta blockers
Angina Beta blockers
Stress Beta blockers
Depression Tricyclic antidepressants, SSRIs
Overweight Topiramate, protriptyline
Underweight Tricyclic antidepressants (nortriptyline, protriptyline)
Epilepsy Valproic acid, topiramate
Mania Valproic acid
SSRIs = selective serotonin reuptake inhibitors
Propranolol, timolol, methysergide, valproic acid, and topiramate (Topamax) have
been approved by the FDA for migraine prophylaxis. However, a 2009 report
suggested that longterm topiramate use in pediatric patients can cause metabolic
acidosis and hypokalemia; the risk was deemed mild but statistically significant.[100]
Misra et al reported that in migraineurs with allodynia, prophylactic therapy with
divalproex and amitriptyline were equally effective in relieving allodynia. In study
patients, the presence of allodynia was related to the duration, severity, and
frequency of migraine and to female gender.[101]
The NSAID naproxen sodium has also been used for prophylaxis. In controlled
clinical trials, naproxen sodium demonstrated better efficacy than placebo and
similar efficacy to propranolol. However, this agent should be reserved for shortterm
use, such as for menstrual migraines.[102] Tolfenamic acid has also been tried for
migraine prophylaxis, but its clinical efficacy is not as good as that of beta blockers,
valproate, or methysergide.
Of note, an open pilot study reported that quetiapine is effective for migraine
prophylaxis in patients with migraine refractory to treatment with standard therapies
(eg, atenolol, nortriptyline, flunarizine). The authors stated that controlled studies
would be necessary to confirm their observations.[103]
Classes of prophylactic drugs
The 3 principal classes of medications that are effective for migraine prevention are
as follows:
Antiepileptics
Antidepressants
Antihypertensives
For any of these prophylactic agents, prophylaxis should not be considered a failure
until it has been given at the maximum tolerable dose for at least 30 days.
Antiepileptics

Antiepileptics are generally well tolerated. The main adverse effects of topiramate
are weight loss and dysesthesia.[104] Valproic acid (Depakote) is useful as a firstline
agent. It is a good mood stabilizer and can benefit patients with concomitant mood
swings. However, it can cause weight gain, hair loss, and polycystic ovary disease;
therefore, it may not be ideal for young female patients who have a tendency to gain
weight.
Valproic acid also carries substantial risks in pregnancy; it may be best suited for
women who have had tubal ligation and who cannot tolerate calcium channel
blockers because of dizziness. Data for other antiepileptics (eg, gabapentin,[105]
lamotrigine, oxcarbazepine) are limited in migraine.
Topiramate is approved in the U.S. for migraine prophylaxis in adults and
adolescents aged 12 years or older. The safety and effectiveness of topiramate in
preventing migraine headaches in adolescents were established in a clinical trial of
103 participants. Frequency of migraine decreased by approximately 72% in treated
patients, compared with 44% in participants receiving placebo.[106, 107]
Antidepressants
Tricyclic antidepressants are good secondline alternatives because of their
adverseeffect profile and efficacy. Headtohead comparisons of agents in this class
have not been conducted, but amitriptyline and nortriptyline are commonly used.
Although selective serotonin reuptake inhibitors (SSRIs) are widely used, data
regarding their efficacy in migraine prevention are lacking; consequently, SSRIs are
not recommended for migraine prevention. However, limited data do support the use
of serotonin/norepinephrine reuptake inhibitors (SNRIs) such as duloxetine
(Cymbalta) and venlafaxine (Effexor) for migraine prevention.
Antihypertensives
Antihypertensives such as beta blockers should be tailored if the patient is young
and anxious. Moreover, they may not be the ideal choice for elderly patients or
patients with depression, thyroid problems, or diabetes. Calcium channel blockers
are another possible choice of treatment. Angiotensinconverting enzyme (ACE)
inhibitors (eg, lisinopril) and angiotensinreceptor blockers (eg, candesartan)[108]
have also been shown to be effective for migraine prevention.[109]
Botulinum toxin
Botulinum toxin A (onabotulinumtoxinA; BOTOX®) may be beneficial in patients with
intractable, chronic migraine that has failed to respond to at least 3 conventional
preventive medications. The injections are administered to the scalp and temple.
They may reduce the frequency and severity of migraine attacks after 23 months of
injections.
The injections are expensive and must be administered every 23 months to
maintain their effectiveness. The most appropriate duration of prophylactic therapy
has not been determined. In most patients who are receiving prophylaxis, therapy

must be continued for at least 36 months.
Multiple trials of onabotulinumtoxinA for migraine prevention have been conducted,
with mixed results.[110] A review by SchulteMattler and MartinezCastrillo found no
evidence of a beneficial effect from botulinum toxin. These authors do not
recommend the widespread use of botulinum toxin therapy in headaches.[111]
More recently, however, 2 multicenter, placebocontrolled trials included in the Phase
3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program
found onabotulinumtoxinA to be effective for headache prophylaxis in adults with
chronic migraine. Nearly 1400 patients were included in the results. Secondary
benefits included significantly reduced headacherelated disability and improved
functioning, vitality, and overall healthrelated quality of life.[112]
In 2016, the American Academy of Neurology updated its 2008 guidelines on using
botulinum toxin for brain disorders. Botulinum toxin A is now recommended for the
management of chronic migraine, defined as attacks lasting 4 or more hours on at
least 15 days each month for 3 months. Botulinum toxin A is not recommended for
less frequent, "episodic" migraine.[113]
Devices
In March 2014, the FDA approved the first device for the preventive treatment of
migraine headaches for adults, a transcutaneous electrical nerve stimulation (TENS)
device that is worn for 20 minutes a day. The device fits across the forehead and
over the ears and stimulates the trigeminal nerve with a selfadhesive electrode in
the center of the forehead. Approval was based on a study of 67 migraine patients in
which the device reduced the number of migraine days per month and medication
use, and on a patient satisfaction study of 2313 device users, in which more than
53% of patients were satisfied with the device.[114]
Status Migrainosus Treatment
Approximately 40% of all migraine attacks do not respond to a given triptan or any
other substance. If all else fails, an intractable migraine attack (status migrainosus),
that is, an attack lasting longer than 72 hours, should be addressed in an urgent
care or emergency department. In rare cases, patients may need to be hospitalized
for a short period and may need to be treated with intravenous valproate or
dihydroergotamine (intravenously/subcutaneously/intramuscularly) for a few days.
[115]
Treatment of Menstrual Migraine
Abortive therapy for menstrual migraine is the same as for nonmenstrual migraine.
Patients with frequent and severe attacks may benefit from shortterm, perimenstrual
use of preventive agents (eg, frovatriptan[116] ). Patients with menstrual and
nonmenstrual migraine who are receiving continuous preventive therapy and
experiencing breakthrough menstrual migraine headaches may benefit from

perimenstrual elevation of the dose of the preventive medication.
Patients who do not respond to standard preventive measures may benefit from
hormonal therapy. Perimenstrual estrogen supplementation with estradiol (0.5 mg
orally twice a day, or a 1mg transdermal patch) may be beneficial. A study by De
Leo et al of oral contraceptive use in women with menstrual migraine without aura
found that a regimen of 24 ethinyl estradiol/drospirenone pills and 4 inert pills was
more effective than a regimen of 21 active pills and 7 inert pills.[117]
Complementary and Alternative Treatments
Interest in the use of complementary and alternative medicine (CAM) by headache
patients is widespread. A 2002 survey showed that more than 85% of headache
patients use CAM therapies and 60% felt they provided some relief.[118] Overall,
more than 70% of patients who use CAM do not tell their doctors about it.
Some CAM techniques have good scientific evidence of benefit and have been
proven by studies to be effective in preventing migraine. Biofeedback and behavioral
therapy should be part of the standard of care for a difficult migraine patient.
Good studies have demonstrated the effectiveness of the herb butterbur (Petasites
hybridus) in preventing migraines.[119] A guideline from the American Academy of
Neurology and the American Headache Society (AAN/AHS) recommends offering
butterbur to patients with migraine to reduce the frequency and severity of migraine
attacks (level A recommendation).[102] Patients on butterbur require monitoring of
liver enzymes.
The AAN/AHS found moderate evidence of effectiveness for riboflavin (vitamin B2),
magnesium, and feverfew. A 3month, randomized, controlled trial of highdose
riboflavin (400 mg) found that riboflavin was superior to placebo in reducing attack
frequency and headache days.[120]
A randomized, controlled trial of coenzyme Q10 (CoQ10) documented that CoQ10 is
effective and well tolerated for migraine prophylaxis.[121] Results of a trial in children
and adolescents suggested that prophylaxis with CoQ10 may lead to earlier
improvement in headache severity than does placebobased prophylaxis, but the
trial found no longterm difference in headache outcomes between the CoQ10 and
placebo groups.[122]
Melatonin has also been used for migraine prevention. Alstadhaug et al conducted a
randomized, controlled, 8week trial of prolongedrelease melatonin (2 mg 1 hour
before bedtime) in adult patients experiencing 27 migraine attacks per month.
Although the investigators found that in the melatonin group the average attack
frequency fell from 4.2 to 2.8 per month, this result was not significantly superior
statistically to the reduction seen with placebo.[116]
A variety of other CAM techniques are not bolstered by solid scientific data, but they
may be perceived to be of benefit to patients.[123] Techniques that some patients use
for headache relief include the following:

Body work Eg, chiropractic, massage, and craniosacral therapy [124] )
Nutritional/herbal supplements Eg, vitamins and herbs
Yoga [125]
Acupressure and acupuncture [126]
Biofeedback [127, 128]
Overall, scientific evidence on the efficacy of these modalities is lacking, partly due
to the poor design and/or poor quality of the studies performed to date.
Mindfulnessbased stress reduction and home meditation have been studied as a
method to reduce the pain and improve healthrelated quality of life in patients with
chronic pain syndromes. While this method proved effective for chronic arthritis
patients, it was not deemed effective in patients with chronic headache/migraine or
fibromyalgia.[129]
The advantages of CAM therapies are that many of these remedies have no
adverse effects, they advocate a selfhelp technique that is attractive to patients, and
they offer a holistic approach. The practitioners often spend significant time with their
patients, and that in itself makes the patient feel as if he or she has been given
careful attention.
The disadvantages of CAM therapies include the lack of standardization of either the
practice or the dispensing of the therapies and techniques. In addition, for many of
these modalities, no standard format exists to ensure that practitioners are
adequately trained in the techniques they use.
Surgical Care
Surgical therapy for migraine is highly controversial. In a study of 60 patients,
Dirnberger and Becker reported that corrugator muscle resection produced total
relief of migraine in 28.3% of patients, essential improvement in 40%, and minimal
or no change in 31.7%. The more severe their migraine, however, the less likely
patients were to experience improvement. In addition, 11 patients who had a very
favorable shortterm response experienced a gradual return of their headaches to
preoperative intensity within about 4 weeks postoperatively.[130]
Diet
The significance of diet as a migraine trigger is controversial.[131] Nevertheless,
individual patients often can identify these triggers. Common dietary triggers include
the following:
Alcohol Particularly wine and beer
Caffeine overuse or caffeine withdrawal
Chocolate
Aspartame eg, NutraSweet and Equal
Monosodium glutamate (MSG) May be found in Asian food, canned soup,
frozen or processed foods, and the seasoning product Accent

Fruits Citrus fruits, bananas, avocados, and dried fruit
Nuts Peanuts, soy nuts, and soy sauce
Tyramine, a biogenic amine that accumulates in food as it ages, may provoke
migraine. Sources include the following:
Dairy Aged cheese
Meat Bacon, sausage, luncheon meat, deli meat, pepperoni, and smoked or
cured meat
Pickled foods
Heavily yeasted breads Eg, sourdough
Vinegars Especially wine vinegar
Some types of beans
Nutraceuticals shown to be effective in randomized clinical trials include the
aforementioned vitamin B2, CoQ10, magnesium, and butterbur (Petadolex).[132]
Activity
One study of exercise for migraine prevention (40 minutes 3 times weekly for 3
months) reported a mean attack reduction of 0.93 during the final month of
treatment, which was not significantly different from the reductions achieved in the
control groups using topiramate or a relaxation program.[133] However, most studies
of aerobic exercise in migraine patients have not found a significant reduction of
headache attacks or headache duration, although regular exercise has been shown
to reduce pain intensity in many patients.[134]
Novel Treatments and Future Drugs
Tonabersat is a novel benzopyran compound that markedly reduces cortical
spreading depression (CSD) and CSDassociated events by inhibiting gapjunction
communication between neurons and satellite glial cells in the trigeminal ganglion.
[135] In a randomized, doubleblind, placebocontrolled crossover trial, preventive
therapy with tonabersat reduced the frequency of aura attacks with or without
headache but had no efficacy on nonaura attacks.[16]
The pipeline of future compounds for the treatment of acute migraine headaches
also includes the following medications:
Transient receptor potential vanilloid type 1 antagonists
Prostaglandin E receptor 4 receptor antagonists
Serotonin 5HT1(F) receptor agonists
Nitric oxide synthase inhibitors
The immediate future of preventive treatment for migraine headaches will likely
involve glutamate NmethylDaspartic acid (NMDA) receptor antagonists and gap
junction blockers.[136]

Guidelines

Contributor Information and Disclosures
Author
Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center
Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic
Medicine, American Clinical Neurophysiology Society, American Medical Association
Disclosure: Nothing to disclose.
Chief Editor
Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke
Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association
Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2.
Acknowledgements
Michelle Blanda, MD Chair, Department of Emergency Medicine, Summa Health System Akron City/St. Thomas Hospital; Professor of Emergency Medicine, Northeastern
Ohio Universities College of Medicine
Michelle Blanda, MD, is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Ronald Braswell, MD Associate Professor, Department of Ophthalmology, University of AlabamaBirmingham
Ronald Braswell, MD is a member of the following medical societies: American Academy of Ophthalmology and North American NeuroOphthalmology Society
Joseph Carcione Jr, DO, MBA Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester
Neuromuscular Care, PC; Medical Director, Oxford Health Plans
Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology
Jane W Chan, MD Professor of Neurology/Neuroophthalmology, Department of Medicine, Division of Neurology, University of Nevada School of Medicine
Jane W Chan, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American Medical Association,
North American NeuroOphthalmology Society, and Phi Beta Kappa
Pamela L Dyne, MD Professor of Clinical Medicine/Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician,
Department of Emergency Medicine, Olive ViewUCLA Medical Center
Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for
Academic Emergency Medicine

Robert A Egan, MD Director of NeuroOphthalmology, St Helena Hospital
Robert A Egan, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, North American NeuroOphthalmology
Society, and Oregon Medical Association
Eric R Eggenberger, DO, MS, FAAN Professor, ViceChairman, Department of Neurology and Ophthalmology, Colleges of Osteopathic Medicine and Human Medicine,
Michigan State University; Director of Michigan State University Ocular Motility Laboratory; Director of National Multiple Sclerosis Society Clinic, Michigan State University
Eric R Eggenberger, DO, MS, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American
Osteopathic Association, and North American NeuroOphthalmology Society
Jacqueline Freudenthal, MD CoInvestigator, Ophthalmic Consultants Centre, Toronto
Jacqueline Freudenthal, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology,
and Canadian Ophthalmological Society
Deborah I Friedman, MD, MPH Professor of Ophthalmology and Neurology, University of Rochester School of Medicine and Dentistry; Consulting Staff, Strong Memorial
Hospital
Deborah I Friedman, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American Headache
Society, American Neurological Association, Association for Research in Vision and Ophthalmology, North American NeuroOphthalmology Society, Society for
Neuroscience, and United Council of Neurologic Subspecialties, Certification in Headache Medicine
Disclosure: MAP Pharmaceuticals Grant/research funds Site PI (through university); AGA Medical Grant/research funds Site PI (through university); Teva Grant/research
funds Site PI (through university); Pfizer Grant/research funds Site PI; Neurology Reviews Honoraria Editorial board; Merck Grant/research funds Site PI
J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of
Emergency Physicians, and Society for Academic Emergency Medicine
Edsel Ing, MD, FRCSC Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Consulting Staff, Toronto East
General Hospital, Canada
Edsel Ing, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and
Strabismus, American Society of Ophthalmic Plastic and Reconstructive Surgery, Canadian Ophthalmological Society, North American NeuroOphthalmology Society, and
Royal College of Physicians and Surgeons of Canada
David Y Ko, MD Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of Southern
California

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society,
and American Headache Society
Disclosure: GSK Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Lundbeck Consulting fee Consulting; Westward Consulting fee Consulting
Amelito Malapira, MD Consulting Staff, Northwest Neurology
Jorge E Mendizabal, MD Consulting Staff, Corpus Christi Neurology
Jorge E Mendizabal, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, National Stroke Association, and
Stroke Council of the American Heart Association
Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of Cleveland
Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society
for Academic Emergency Medicine
Joseph Quinn, MD Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University
Hampton Roy Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and PanAmerican Association
of Ophthalmology
Soma SahaiSrivastava, MD Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, Keck School of
Medicine of the University of Southern California
Soma SahaiSrivastava, MD is a member of the following medical societies: American Academy of Neurology, American Headache Society, and American Medical
Association
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; EditorinChief, Medscape Drug Reference
Disclosure: Medscape Reference Salary Employment
Jeff T Wright, MD Instructor, Department of Emergency Medicine, Summa Health System; Corporation President and Consulting Staff, Summa Emergency Associates, Inc
Jeff T Wright, MD is a member of the following medical societies: American College of Emergency Physicians
Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro
Ophthalmology Society
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