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

Updated: Jun 22, 2016

Approach ConsiderationsMigraine treatment involves acute (abortive) and preventive (prophylactic) therapy.Patients with frequent attacks usually require both. Measures directed towardreducing migraine triggers are also generally advisable.

Acute treatment aims to reverse, or at least stop, the progression of a headache thathas started. Preventive treatment, which is given even in the absence of aheadache, aims to reduce the frequency and severity of the migraine attack, makeacute attacks more responsive to abortive therapy, and perhaps also improve thepatient's quality of life. An overview of migraine treatment is shown in the imagebelow.

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 onthe increased risk of stroke with smoking and oral contraceptive use.

A neurologist, neuroophthalmologist, and/or neurosurgeon should be consulted asdeemed clinically appropriate for the treatment of patients with migraine.

Emergency Department ConsiderationsEmergency medical services personnel should transport patients in a way thatminimizes visual and auditory stimulation. Once in the emergency department (ED),most patients should not receive opiate analgesics until a thorough neurologicexamination 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 EDbecause 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. Althoughnarcotics remain the most frequently administered medication for patients withmigraine and for ED patients with headache, evidence suggests that they arepotentially 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 otherprimary headache reported headache recurrence within 48 hours of ED discharge;in this study, naproxen 500 mg and oral sumatriptan 100 mg provided comparablerelief of postED recurrent migraine.[82]

Hospital admission for migraine may be indicated for the following:

Treatment of severe nausea, vomiting, and subsequent dehydrationTreatment of severe, refractory migraine pain (ie, status migrainosus)Detoxification from overuse of combination analgesics, ergots, or opioids

Reduction of Migraine TriggersPatients should avoid factors that precipitate a migraine attack (eg, lack of sleep,fatigue, stress, certain foods, use of vasodilators). Encourage patients to use a dailydiary to document the headaches. This is an effective and inexpensive tool to followthe 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 tomodify, change, or discontinue its use for a trial period.[83] Similarly, when hormonereplacement therapy is a suspected trigger, patients should reduce dosages, ifpossible. If headaches persist, consider discontinuing hormone therapy.

Nonpharmacologic TherapyBiofeedback, cognitivebehavioral therapy, and relaxation therapy are frequentlyeffective against migraine headaches and may be used adjunctively withpharmacologic treatments. Occipital nerve stimulators may be helpful in patientswhose 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 withaura for use in patients aged 18 years and older. Users hold the device with bothhands to the back of the head and press a button to release a pulse of magneticenergy that stimulates the occipital cortex. The recommended daily usage of thedevice 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 thedevice 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 thedevice were painfree, compared with 10% of the control group.

Contraindications and precautions regarding the use of the Cerena TMS include thefollowing[84, 85] :

Do not use for patients with any metal in the head, neck, or upper body that isattracted by a magnetDo 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 apersonal or family history of seizures

Trials of nonpharmacologic management have produced average reduction inmigraines of 4050%, closely paralleling results obtained in trials of preventivedrugs; however, the evidence base for nonpharmacologic and pharmacologicprevention remains limited. A 16month randomized, placebocontrolled trial byHolryod et al found that the combination of betablocker therapy and behavioralmanagement improved outcomes in patients with frequent migraines, while neitherintervention was effective by itself.[88]

Abortive TherapyNumerous abortive medications are used for migraine. The choice for an individualpatient depends on the severity of the attacks, associated symptoms such asnausea and vomiting, comorbid problems, and the patient's treatment response. Astratified 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 anew window)

Moderate Severe Extremely SevereNSAIDs Naratriptan DHE (IV)Isometheptene Rizatriptan OpioidsErgotamine Sumatriptan (SC,NS) Dopamine antagonistsNaratriptan 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 providedrelief for mild to moderately severe headaches and sometimes even for severeheadaches.[89] Acute treatment is most effective when given within 15 minutes ofpain onset and when pain is mild.[90]

Analgesics used in migraine include acetaminophen, NSAIDs, and narcoticanalgesics (eg, oxycodone, morphine sulfate). Propoxyphene (Darvon) was formerlyused; however, propoxyphene products were withdrawn from the United Statesmarket in 2010, because this agent can cause prolonged PR interval, widened QRScomplex, and prolonged QT interval at therapeutic doses. For more information, seeMedWatch safety information, from the US Food and Drug Administration (FDA).

For more severe pain, 5hydroxytryptamine–1 (5HT1) agonists (triptans) and/oropioid analgesics are used, either alone or in combination with dopamineantagonists (eg, prochlorperazine [Compazine]). The use of abortive medicationsmust be limited to 23 days a week to prevent development of a rebound headachephenomenon.

Intravenous metoclopramide is recognized as an effective therapy for acutemigraine, but the optimal dosing has not been established. A study by Friedman etal determined that 20 or 40 mg of metoclopramide is no better in the treatment ofacute migraine than 10 mg of the drug.[91]

A systematic review by Taggart et al found that ketorolac is an effective alternativeagent for the relief of acute migraine headache in the ED. Ketorolac provides painrelief similar to that with meperidine (with less potential for addiction) and is moreeffective than sumatriptan; however, it may not be as effective asmetoclopramide/phenothiazine agents. Sideeffect profiles were similar withketorolac and these other agents.[92]

Triptans and ergot alkaloids

The 2 categories of migrainespecific oral medications are triptans and ergotalkaloids. The specific ergot alkaloids include ergotamine and dihydroergotamine(DHE).[93] The specific triptans include the following[94] :

SumatriptanRizatriptanZolmitriptanNaratriptanAlmotriptanEletriptanFrovatriptan

Although the triptans share a common mechanism of action, they differ in theavailable routes of administration, onset of action, and duration of action. Routes ofadministration include oral, intranasal, subcutaneous, and intramuscular.Transdermal patches have proved effective for the delivery of sumatriptan, and onesuch product has received FDA approval.[95] The sumatriptan iontophoretictransdermal system (Zecuity, NuPathe Inc) was approved by the FDA in January2013 for the acute treatment of migraine with or without aura in adults. The singleuse patch also treats migrainerelated nausea. In phase 3 trials involving 800patients, the patches safely and effectively relieved migraine pain, migrainerelatednausea, sonophobia, and photophobia within 2 hours of activation.[95]

The FDA approved a lowdose intranasal sumatriptan powder for migraine inJanuary 2016. The product consists of 22 mg of sumatriptan powder and is the firstbreathpowered intranasal medication delivery system to treat migraines. Approvalwas based on data from phase 2 and phase 3 trials, reference data on the use ofsumatriptan, 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 berepeated in 2 hours as needed, with a maximum of 2 doses daily. While differentformulations of a specific triptan may be used in the same 24hour period, only 1triptan may be used during this time frame.

The longeracting triptans (eg, frovatriptan, naratriptan) may be used continuouslyfor several days (miniprophylaxis) to treat menstrual migraine. Triptans should notbe used more than 3 days weekly, to avoid transformed migraine and medicationoveruse headache.

The effectiveness and tolerability of triptans varies among patients. Lack of responseor 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 coronaryvasospasm from triptan use is exceedingly rare. However, triptans should not betaken by patients with known or suspected coronary artery disease, as they mayincrease risk of myocardial ischemia, infarction, or other cardiac or cerebrovascularevents.

The dose of rizatriptan must be reduced to 5 mg in patients taking propranolol.Sumatriptan, zolmitriptan, and rizatriptan are primarily metabolized by monoamineoxidase (MAO) and should be avoided in patients taking MAOA inhibitors.

The first combination product of a triptan and an NSAID, Treximet, was approved bythe FDA in 2008. Treximet contains sumatriptan and naproxen sodium. In 2randomized, doubleblind, multicenter, parallelgroup trials, a significantly greaterpercentage of patients remained pain free for 24 hours postdose after a single doseof Treximet (25% and 23%) than after use of placebo (8% and 7%) or eithersumatriptan (16% and 14%) or naproxen sodium (10%) alone.[98]

Patients with severe headaches need subcutaneous, intravenous, or oralformulations of an ergot alkaloid or triptan. Do not administer vasoconstrictors, suchas 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 emesisassociated with acute migraine attacks. Patients with severe nausea and vomiting atthe onset of an attack may respond best to intravenous prochlorperazine. Thesepatients may be dehydrated, and adequate hydration is necessary.

Antiemetics are commonly combined with diphenhydramine to minimize the risk ofakathisia. This combination of drugs has been found to be superior to subcutaneoussumatriptan when given intravenously in emergency patients.[99]

Prophylactic TherapyThe following may be considered indications for prophylactic migraine therapy:

Frequency of migraine attacks is greater than 2 per monthDuration of individual attacks is longer than 24 hoursThe headaches cause major disruptions in the patient’s lifestyle, withsignificant disability that lasts 3 or more daysAbortive therapy fails or is overusedSymptomatic medications are contraindicated or ineffectiveUse of abortive medications more than twice a weekMigraine variants such as hemiplegic migraine or rare headache attacksproducing profound disruption or risk of permanent neurologic injury [5]

The goals of preventive therapy are as follows:

Reduce attack frequency, severity, and/or durationImprove responsiveness to acute attacksReduce disability

Currently, the major prophylactic medications for migraine work via one of thefollowing mechanisms:

5HT2 antagonism MethysergideRegulation of voltagegated ion channels Calcium channel blockersModulation of central neurotransmitters Beta blockers, tricyclicantidepressantsEnhancing gammaaminobutyric acidergic (GABAergic) inhibition Valproicacid, gabapentin

Another notable mechanism is alteration of neuronal oxidative metabolism byriboflavin and reduction of neuronal hyperexcitability by magnesium replacement.

As with abortive medications, the selection of a preventive medication must take intoconsideration 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 initiationof 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 lineHigh 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 newwindow)

Comorbid Condition MedicationHypertension Beta blockersAngina Beta blockersStress Beta blockersDepression Tricyclic antidepressants, SSRIsOverweight Topiramate, protriptylineUnderweight Tricyclic antidepressants (nortriptyline, protriptyline)Epilepsy Valproic acid, topiramateMania Valproic acidSSRIs = selective serotonin reuptake inhibitors

Propranolol, timolol, methysergide, valproic acid, and topiramate (Topamax) havebeen approved by the FDA for migraine prophylaxis. However, a 2009 reportsuggested that longterm topiramate use in pediatric patients can cause metabolicacidosis and hypokalemia; the risk was deemed mild but statistically significant.[100]

Misra et al reported that in migraineurs with allodynia, prophylactic therapy withdivalproex and amitriptyline were equally effective in relieving allodynia. In studypatients, the presence of allodynia was related to the duration, severity, andfrequency of migraine and to female gender.[101]

The NSAID naproxen sodium has also been used for prophylaxis. In controlledclinical trials, naproxen sodium demonstrated better efficacy than placebo andsimilar efficacy to propranolol. However, this agent should be reserved for shorttermuse, such as for menstrual migraines.[102] Tolfenamic acid has also been tried formigraine 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 migraineprophylaxis in patients with migraine refractory to treatment with standard therapies(eg, atenolol, nortriptyline, flunarizine). The authors stated that controlled studieswould be necessary to confirm their observations.[103]

Classes of prophylactic drugs

The 3 principal classes of medications that are effective for migraine prevention areas follows:

AntiepilepticsAntidepressantsAntihypertensives

For any of these prophylactic agents, prophylaxis should not be considered a failureuntil 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 topiramateare weight loss and dysesthesia.[104] Valproic acid (Depakote) is useful as a firstlineagent. It is a good mood stabilizer and can benefit patients with concomitant moodswings. 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 gainweight.

Valproic acid also carries substantial risks in pregnancy; it may be best suited forwomen who have had tubal ligation and who cannot tolerate calcium channelblockers 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 andadolescents aged 12 years or older. The safety and effectiveness of topiramate inpreventing migraine headaches in adolescents were established in a clinical trial of103 participants. Frequency of migraine decreased by approximately 72% in treatedpatients, compared with 44% in participants receiving placebo.[106, 107]

Antidepressants

Tricyclic antidepressants are good secondline alternatives because of theiradverseeffect profile and efficacy. Headtohead comparisons of agents in this classhave not been conducted, but amitriptyline and nortriptyline are commonly used.

Although selective serotonin reuptake inhibitors (SSRIs) are widely used, dataregarding their efficacy in migraine prevention are lacking; consequently, SSRIs arenot recommended for migraine prevention. However, limited data do support the useof 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 youngand anxious. Moreover, they may not be the ideal choice for elderly patients orpatients with depression, thyroid problems, or diabetes. Calcium channel blockersare 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 withintractable, chronic migraine that has failed to respond to at least 3 conventionalpreventive medications. The injections are administered to the scalp and temple.They may reduce the frequency and severity of migraine attacks after 23 months ofinjections.

The injections are expensive and must be administered every 23 months tomaintain their effectiveness. The most appropriate duration of prophylactic therapyhas 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 noevidence of a beneficial effect from botulinum toxin. These authors do notrecommend the widespread use of botulinum toxin therapy in headaches.[111]

More recently, however, 2 multicenter, placebocontrolled trials included in the Phase3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical programfound onabotulinumtoxinA to be effective for headache prophylaxis in adults withchronic migraine. Nearly 1400 patients were included in the results. Secondarybenefits included significantly reduced headacherelated disability and improvedfunctioning, vitality, and overall healthrelated quality of life.[112]

In 2016, the American Academy of Neurology updated its 2008 guidelines on usingbotulinum toxin for brain disorders. Botulinum toxin A is now recommended for themanagement of chronic migraine, defined as attacks lasting 4 or more hours on atleast 15 days each month for 3 months. Botulinum toxin A is not recommended forless frequent, "episodic" migraine.[113]

Devices

In March 2014, the FDA approved the first device for the preventive treatment ofmigraine headaches for adults, a transcutaneous electrical nerve stimulation (TENS)device that is worn for 20 minutes a day. The device fits across the forehead andover the ears and stimulates the trigeminal nerve with a selfadhesive electrode inthe center of the forehead. Approval was based on a study of 67 migraine patients inwhich the device reduced the number of migraine days per month and medicationuse, and on a patient satisfaction study of 2313 device users, in which more than53% of patients were satisfied with the device.[114]

Status Migrainosus TreatmentApproximately 40% of all migraine attacks do not respond to a given triptan or anyother 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 urgentcare or emergency department. In rare cases, patients may need to be hospitalizedfor a short period and may need to be treated with intravenous valproate ordihydroergotamine (intravenously/subcutaneously/intramuscularly) for a few days.[115]

Treatment of Menstrual MigraineAbortive therapy for menstrual migraine is the same as for nonmenstrual migraine.Patients with frequent and severe attacks may benefit from shortterm, perimenstrualuse of preventive agents (eg, frovatriptan[116] ). Patients with menstrual andnonmenstrual migraine who are receiving continuous preventive therapy andexperiencing 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 fromhormonal therapy. Perimenstrual estrogen supplementation with estradiol (0.5 mgorally twice a day, or a 1mg transdermal patch) may be beneficial. A study by DeLeo et al of oral contraceptive use in women with menstrual migraine without aurafound that a regimen of 24 ethinyl estradiol/drospirenone pills and 4 inert pills wasmore effective than a regimen of 21 active pills and 7 inert pills.[117]

Complementary and Alternative TreatmentsInterest in the use of complementary and alternative medicine (CAM) by headachepatients is widespread. A 2002 survey showed that more than 85% of headachepatients 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 beenproven by studies to be effective in preventing migraine. Biofeedback and behavioraltherapy should be part of the standard of care for a difficult migraine patient.

Good studies have demonstrated the effectiveness of the herb butterbur (Petasiteshybridus) in preventing migraines.[119] A guideline from the American Academy ofNeurology and the American Headache Society (AAN/AHS) recommends offeringbutterbur to patients with migraine to reduce the frequency and severity of migraineattacks (level A recommendation).[102] Patients on butterbur require monitoring ofliver enzymes.

The AAN/AHS found moderate evidence of effectiveness for riboflavin (vitamin B2),magnesium, and feverfew. A 3month, randomized, controlled trial of highdoseriboflavin (400 mg) found that riboflavin was superior to placebo in reducing attackfrequency and headache days.[120]

A randomized, controlled trial of coenzyme Q10 (CoQ10) documented that CoQ10 iseffective and well tolerated for migraine prophylaxis.[121] Results of a trial in childrenand adolescents suggested that prophylaxis with CoQ10 may lead to earlierimprovement in headache severity than does placebobased prophylaxis, but thetrial found no longterm difference in headache outcomes between the CoQ10 andplacebo groups.[122]

Melatonin has also been used for migraine prevention. Alstadhaug et al conducted arandomized, controlled, 8week trial of prolongedrelease melatonin (2 mg 1 hourbefore bedtime) in adult patients experiencing 27 migraine attacks per month.Although the investigators found that in the melatonin group the average attackfrequency fell from 4.2 to 2.8 per month, this result was not significantly superiorstatistically to the reduction seen with placebo.[116]

A variety of other CAM techniques are not bolstered by solid scientific data, but theymay be perceived to be of benefit to patients.[123] Techniques that some patients usefor headache relief include the following:

Body work Eg, chiropractic, massage, and craniosacral therapy [124] )Nutritional/herbal supplements Eg, vitamins and herbsYoga [125]

Acupressure and acupuncture [126]

Biofeedback [127, 128]

Overall, scientific evidence on the efficacy of these modalities is lacking, partly dueto the poor design and/or poor quality of the studies performed to date.

Mindfulnessbased stress reduction and home meditation have been studied as amethod to reduce the pain and improve healthrelated quality of life in patients withchronic pain syndromes. While this method proved effective for chronic arthritispatients, it was not deemed effective in patients with chronic headache/migraine orfibromyalgia.[129]

The advantages of CAM therapies are that many of these remedies have noadverse effects, they advocate a selfhelp technique that is attractive to patients, andthey offer a holistic approach. The practitioners often spend significant time with theirpatients, and that in itself makes the patient feel as if he or she has been givencareful attention.

The disadvantages of CAM therapies include the lack of standardization of either thepractice or the dispensing of the therapies and techniques. In addition, for many ofthese modalities, no standard format exists to ensure that practitioners areadequately trained in the techniques they use.

Surgical CareSurgical therapy for migraine is highly controversial. In a study of 60 patients,Dirnberger and Becker reported that corrugator muscle resection produced totalrelief of migraine in 28.3% of patients, essential improvement in 40%, and minimalor no change in 31.7%. The more severe their migraine, however, the less likelypatients were to experience improvement. In addition, 11 patients who had a veryfavorable shortterm response experienced a gradual return of their headaches topreoperative 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 includethe following:

Alcohol Particularly wine and beerCaffeine overuse or caffeine withdrawalChocolateAspartame eg, NutraSweet and EqualMonosodium 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 fruitNuts Peanuts, soy nuts, and soy sauce

Tyramine, a biogenic amine that accumulates in food as it ages, may provokemigraine. Sources include the following:

Dairy Aged cheeseMeat Bacon, sausage, luncheon meat, deli meat, pepperoni, and smoked orcured meatPickled foodsHeavily yeasted breads Eg, sourdoughVinegars Especially wine vinegarSome types of beans

Nutraceuticals shown to be effective in randomized clinical trials include theaforementioned vitamin B2, CoQ10, magnesium, and butterbur (Petadolex).[132]

ActivityOne study of exercise for migraine prevention (40 minutes 3 times weekly for 3months) reported a mean attack reduction of 0.93 during the final month oftreatment, which was not significantly different from the reductions achieved in thecontrol groups using topiramate or a relaxation program.[133] However, most studiesof aerobic exercise in migraine patients have not found a significant reduction ofheadache attacks or headache duration, although regular exercise has been shownto reduce pain intensity in many patients.[134]

Novel Treatments and Future DrugsTonabersat is a novel benzopyran compound that markedly reduces corticalspreading depression (CSD) and CSDassociated events by inhibiting gapjunctioncommunication between neurons and satellite glial cells in the trigeminal ganglion.[135] In a randomized, doubleblind, placebocontrolled crossover trial, preventivetherapy with tonabersat reduced the frequency of aura attacks with or withoutheadache but had no efficacy on nonaura attacks.[16]

The pipeline of future compounds for the treatment of acute migraine headachesalso includes the following medications:

Transient receptor potential vanilloid type 1 antagonistsProstaglandin E receptor 4 receptor antagonistsSerotonin 5HT1(F) receptor agonistsNitric oxide synthase inhibitors

The immediate future of preventive treatment for migraine headaches will likelyinvolve glutamate NmethylDaspartic acid (NMDA) receptor antagonists and gapjunction blockers.[136]

Guidelines

Contributor Information and DisclosuresAuthorJasvinder 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 ElectrodiagnosticMedicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Chief EditorHelmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU StrokeCenter

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.

AcknowledgementsMichelle Blanda, MD Chair, Department of Emergency Medicine, Summa Health System Akron City/St. Thomas Hospital; Professor of Emergency Medicine, NortheasternOhio 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

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Joseph Carcione Jr, DO, MBA Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central WestchesterNeuromuscular Care, PC; Medical Director, Oxford Health Plans

Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

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 forAcademic Emergency Medicine

Disclosure: Nothing to disclose.

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 NeuroOphthalmologySociety, and Oregon Medical Association

Disclosure: Nothing to disclose.

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, AmericanOsteopathic Association, and North American NeuroOphthalmology Society

Disclosure: Nothing to disclose.

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

Disclosure: Nothing to disclose.

Deborah I Friedman, MD, MPH Professor of Ophthalmology and Neurology, University of Rochester School of Medicine and Dentistry; Consulting Staff, Strong MemorialHospital

Deborah I Friedman, MD, MPH is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American HeadacheSociety, American Neurological Association, Association for Research in Vision and Ophthalmology, North American NeuroOphthalmology Society, Society forNeuroscience, 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/researchfunds 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 ofEmergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Edsel Ing, MD, FRCSC Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Consulting Staff, Toronto EastGeneral Hospital, Canada

Edsel Ing, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology andStrabismus, American Society of Ophthalmic Plastic and Reconstructive Surgery, Canadian Ophthalmological Society, North American NeuroOphthalmology Society, andRoyal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

David Y Ko, MD Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of SouthernCalifornia

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

Disclosure: Nothing to disclose.

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, andStroke Council of the American Heart Association

Disclosure: Nothing to disclose.

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 Societyfor Academic Emergency Medicine

Disclosure: Nothing to disclose.

Joseph Quinn, MD Assistant Professor, Department of Neurology, Portland VA Medical Center, Oregon Health Sciences University

Disclosure: Nothing to disclose.

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 Associationof Ophthalmology

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Soma SahaiSrivastava, MD Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, Keck School ofMedicine 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 MedicalAssociation

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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

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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 NeuroOphthalmology Society

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