eMedicine Specialties > Emergency Medicine > Neurology

Headache, Migraine

Michelle Blanda, MD, Chair, Department of Emergency Medicine, Summa Health System; Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine
Jeff T Wright, MD, Instructor, Department of Emergency Medicine, Summa Health System; Corporation President and Consulting Staff, Summa Emergency Associates, Inc

Updated: Sep 28, 2009

Introduction

Background

Migraine headaches are recurrent headaches that may be unilateral or bilateral. Migraine headaches may occur with or without a prodrome. The aura of a migraine may consist of neurologic symptoms, such as dizziness, tinnitus, scotomas, photophobia, or visual scintillations (eg, bright zigzag lines). The International Headache Society (IHS) redefined and classified headaches to formulate the current categorization, which has been maintained in the second edition.¹ The headache previously described as classic migraine is now known as migraine with aura, and that described as common migraine is now termed migraine without aura. Migraines without aura are the most common, accounting for more than 80% of all migraines.

In April 2000, the US Headache Consortium, a multispecialty group that includes the American College of Emergency Physicians, released evidence-based guidelines for the diagnosis, treatment, and prevention of migraine headaches. Guidelines are also available from the American Academy of Neurology, the National Headache Foundation, and the Canadian Association of Emergency Physicians.^2,3,4

Pathophysiology

The pathophysiology of migraine headaches is not clearly understood. Initially migraine headaches were felt to be of vascular origin. Evidence now supports a neurogenic cause, with neurogenic peptides, such as serotonin and dopamine, as a cause.⁵ These vasoactive neuropeptides stimulate an inflammatory cascade with the release of endothelial cells, mast cells, and platelets. This inflammation causes vasodilation and a perivascular reaction. The serotonin receptor (5-HT) is believed to be the most important receptor in the headache pathway.

Some of the symptoms associated with migraine headaches, such as nausea (80%), vomiting (50%), yawning, irritability, hypotension, and hyperactivity, can be associated with dopamine receptor activation. Dopamine receptor hypersensitivity has been shown experimentally with dopamine agonists such as apomorphine, bromocriptine, and pergolide. Dopamine antagonists, such as metoclopramide (Reglan), haloperidol (Haldol), and prochlorperazine (Compazine), have been shown clinically to treat migraine headaches effectively.

Frequency

United States

An estimated 10-20% of the US population suffers from migraine headaches. Frequency of headaches varies greatly by individual. An estimated 6% of men and 15-17% of women in the United States have migraine. Migraine is the second most common type of headache syndrome in the United States. Tension headaches are the most common.

Sex

Migraines most commonly are found in women, with a 3:1 female-to-male ratio. In childhood, however, migraines are more common in boys than in girls.

Age

The first attack often is in childhood, and incidence increases in adolescence. More than 80% of patients who develop migraines will have a first attack by age 30. Migraines continue through the patient's 30s and 40s. They may begin or occur at any age but are rare after age 50. With increased age, attacks usually decrease in severity and frequency. Age older than 55 years is a strong predictor for intracranial pathology.

Clinical

History

Moderately severe to severe headache with or without a prodrome

• Aura (20%) - A variety of preceding events that begins and ends days to hours prior to the headache itself. Visual aura symptoms are most common. Nonspecific prodrome may precede migraine without an aura.
  • Scotoma (blind spots)
  • Fortification (zig-zag patterns)
  • Scintilla (flashing lights)
  • Unilateral paresthesia/weakness
  • Hallucinations
  • Hemianopsia
• Headache
  • Unilateral, also known as hemicrania (30-40% are bilateral)
  • Throbbing or pulsatile (More than 50% of people who suffer from migraines report nonthrobbing pain at some time during the attack.)
  • Lasts 4-72 hours
• Systemic manifestations
  • Nausea (80-90%)
  • Vomiting (40-60%)
  • Photophobia (80%)
  • Phonophobia (75-80%)
  • Lightheadedness (70%)
• The patient might prefer to be in a quiet and darkened room.
• History factors suggesting a more serious underlying cause of headache
  • The first or worst headache of the patient's life, especially if the headache onset was rapid
  • A change in frequency, severity, or clinical features of the attack from what usually is experienced
  • New progressive headache that persists for days
• Precipitation of headache with Valsalva maneuvers (ie, coughing, sneezing, bearing down)

Physical

• Usually, patients have no specific physical findings other than the physical manifestations of the associated systemic symptoms listed above (photophobia, phonophobia); abnormality on physical examination may suggest another cause of headache.
• The physician must perform a thorough screening neurologic examination.
• Physical examination findings suggesting a more serious cause of headache include the following:
  • Systemic symptoms (eg, myalgia, fever, malaise, weight loss, scalp tenderness, jaw claudication)
  • Focal neurologic abnormalities or confusion, seizures, or any impairment of level of consciousness
  • Focal neurologic findings that occur with the headache and persist temporarily after the pain resolves suggest a migraine variant. In hemiplegic migraine, the patient may have unilateral paralysis or weakness. Aphasia, syncope, and balance problems may be seen in basilar migraines. In ophthalmoplegic migraine, the patient may present with a third nerve palsy, with ocular muscle paralysis, including or sparing the pupillary response, as well as ptosis. Ophthalmic migraines cause a visual disturbance (usually lateral field deficit). This diagnosis is more common in children, with the abnormal motor findings lasting hours to days after the headache.

Causes

Exact etiology is unknown.

• Family history of migraine headaches (70-80%)
• Medications (ie, birth control pills, vasodilators)
• Fatigue or emotional stress
• Specific foods or alcohol
• Exertion

Differential Diagnoses

Other Problems to Be Considered

Brain tumor (increased intracranial pressure)
Opiate dependance/opiate withdrawal headache
Pseudotumor cerebri
Vascular pathology (eg, aneurysm)

Workup

Laboratory Studies

• Laboratory and radiographic evaluation excludes other potential diagnoses in the differential.
  

Imaging Studies

• CT scan of the head is indicated to rule out intracranial mass or hemorrhage in selected or atypical cases. A negative CT scan may miss some small subarachnoid hemorrhages, tumors, and strokes, particularly those in the posterior fossa. A CT scan without intravenous contrast also may miss some aneurysms. MRI and magnetic resonance angiography are more sensitive. Neuroimaging is rarely productive in patients who have a normal neurologic examination. Neuroimaging is not warranted in patients with a diagnosis of migraine who present with a typical event. They are useful if neurologic examination findings are abnormal, the migraine occurs for the first time after age 40 years, the frequency or intensity is increasing, and the accompanying symptoms of the attack change.

Procedures

• Lumbar puncture (LP): In selected patients with appropriately concerning histories, an LP should be performed to rule out infection or small subarachnoid hemorrhage not visible on CT scan of the head.

Treatment

Prehospital Care

Patients should be transported in a way that minimizes visual and auditory stimulation. Most patients should not receive opiate analgesics until a thorough neurologic examination can be completed by the responsible physician.

Emergency Department Care

• While the emergency physician must be able to identify patients with serious headache etiology, note that more than 90% of patients in the ED have migraine, tension, or mixed-type benign headache. Therefore, providing symptomatic relief should be a priority.
• Migraine-specific medications and analgesia are the keys of ED care.
• Rest in a darkened, quiet room is helpful.
• Some patients find cool compresses to painful areas helpful.

Consultations

Neurologic consultation may be required in complex cases, though referral to a primary care provider often is sufficient.

Medication

The goals of pharmacotherapy are to prevent attacks or alter the migraine attack once it is underway. Specifically, this is done by reducing the severity and the duration of the attack. Preventive therapy encompasses these same objectives and decreases the frequency of attacks, improves responsiveness to treatment, and improves function while decreasing disability.

An estimated half of migraine patients stop seeking care for their headaches, partly because they are dissatisfied with therapy.

Analgesics

Initial therapy for patients with infrequent migraines can be simple analgesics.

Acetaminophen and codeine (Tylenol #3)

Drug combination indicated for treatment of mild to moderately severe headache.
Note: Some patients may respond to maximal acetaminophen alone, without codeine.

Dosing

Adult

30-60 mg/dose based on codeine content PO q4-6h or 1-2 tab q4h; not to exceed 12 tab/d (4 g acetaminophen/d)

Pediatric

0.5-1 mg/kg/dose based on codeine content PO q4-6h; 10-15 mg/kg/dose based on acetaminophen content; not to exceed 2.6 g/d of acetaminophen

Interactions

CNS depressants or tricyclic antidepressants increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients dependent on opiates because this substitution may result in acute opiate-withdrawal symptoms; caution in severe renal or hepatic dysfunction

Acetaminophen (Tylenol, Aspirin Free Anacin, Panadol)

DOC for treatment of pain in patients with documented hypersensitivity to aspirin or NSAIDs, in those with upper GI disease, or in those taking oral anticoagulants.

Dosing

Adult

325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d

Pediatric

<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 5 doses in 24 h

Interactions

Rifampin can reduce analgesic effects; barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity

Contraindications

Documented hypersensitivity; G-6-PD deficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; acetaminophen contained in many OTC products, and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose

Aspirin (Anacin, Ascriptin, Bayer Aspirin)

May alleviate migraine attacks by inhibiting prostaglandin synthesis. Mild migraines usually respond well to this medication.

Dosing

Adult

325-650 mg PO q4-6h prn; not to exceed 4 g/d

Pediatric

10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d

Interactions

Antacids and urinary alkalinizers may decrease effects; corticosteroids decrease salicylate serum levels; anticoagulants may cause additive hypoprothrombinemic effects and increased bleeding time; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Contraindications

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma
Because of association with Reye syndrome, do not use in children (<16 y) with flu

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, in those with history of blood coagulation defects, or in those taking anticoagulants

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents may alleviate migraine pain by inhibiting prostaglandin synthesis, reducing serotonin release, and blocking platelet aggregation. Although the effects of NSAIDs in the treatment of migraine pain tend to be patient specific, ibuprofen usually is the DOC for the initial therapy. Other options include naproxen, ketoprofen, and ketorolac.

Naproxen (Anaprox, Naprelan, Naprosyn)

Used for relief of mild to moderately severe headaches. Inhibits inflammatory reactions and pain by decreasing activity of enzyme cyclooxygenase, thus inhibiting prostaglandin synthesis.

Dosing

Adult

500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d

Pediatric

<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d

Interactions

Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (monitor PT closely and instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Ketoprofen (Oruvail, Orudis, Actron)

Used for relief of mild to moderately severe headaches and inflammation.
Administer small dosages initially to patients with small body size, elderly patients, and patients with renal or liver disease.
Doses >75 mg does not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Dosing

Adult

25-50 mg PO q6-8h prn; not to exceed 300 mg/d

Pediatric

<3 months: Not established
3 months to 12 years: 0.1-1 mg/kg PO q6-8h
>12 years: Administer as in adults

Interactions

Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (monitor PT closely and instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Ketorolac (Toradol)

Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors.
PO form available, but no advantage vs other less expensive PO NSAIDs.

Dosing

Adult

30 mg IV single dose (most common route used in ED)
>65 years, renal impairment, or body weight <50 kg: 15 mg IV single dose
30-60 mg IM initially, followed by 15-30 mg q6h prn; not to exceed 5 d of treatment; consider only 1-2 d of treatment in elderly patients because of increased risk of GI bleeding

Pediatric

Not established; recommended dose 0.4-1 mg/kg once

Interactions

Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT in patients taking anticoagulants (monitor PT closely and instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
Do not administer into CNS

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in patients with preexisting renal disease or compromised renal perfusion; low WBC counts (rare) usually return to normal during ongoing therapy; discontinue therapy if persistent leukopenia, granulocytopenia, or thrombocytopenia occurs

5-HT1 Serotonin receptor agonists

The stimulation of 5-HT1 receptors produce a direct vasoconstrictive effect.

Sumatriptan (Imitrex)

Selective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.

Dosing

Adult

25 mg PO; if satisfactory response not observed in 2 h, additional dose of up to 100 mg may be administered; additional doses at intervals of 2 h prn; not to exceed 300 mg/d
6 mg SC; if satisfactory response not observed in 1 h, an additional 6 mg SC may be administered; not to exceed 2 injections/d
Intranasal: Single dose of 5, 10, or 20 mg may be administered in 1 nostril; give 10-mg dose by administering single 5-mg dose in each nostril; if satisfactory response not observed in 2 h, additional dose may be administered; not to exceed 40 mg/d

Pediatric

Not established

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; coadministration or within 2 wk of MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Flushing and chest pain are common;
hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, and bloody diarrhea may occur rarely
Patients with known or suspected coronary artery disease may have increased risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT1 agonists may cause coronary vasospasm)

Zolmitriptan (Zomig, Zomig-ZMT)

Selective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.

Dosing

Adult

2.5 mg or 5 mg PO; repeat dose after 2 h prn; not to exceed 10 mg/d

Pediatric

Not established

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; another serotonin agonist or ergotamine within last 24 h; MAOI within last 2 wk

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Flushing and chest pain are common; hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur
Decrease dose of almotriptan and do not exceed 12.5 mg/d in renal or hepatic impairment

Frovatriptan (Frova)

Used to treat acute migraine. Selective 5-HT_1B/1D receptor agonist with long half-life of 24 h and low headache recurrence rate within 24-hour period of taking the drug. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. Has unique characteristics and benefits in the acute treatment of migraine.

Dosing

Adult

2.5 mg PO once at onset of migraine attack

Pediatric

Not established

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination

Contraindications

Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur

Eletriptan (Relpax)

Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT_1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine.

Dosing

Adult

20-40 mg/dose PO at onset of migraine; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d

Pediatric

<18 years: Not established

Interactions

Potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) may increase toxicity; concurrent administration with ergot-containing drugs may increase vasospastic reactions

Contraindications

Documented hypersensitivity; severe hepatic impairment; age >65 y; administration within 72 h of potent CYP450 3A4 inhibitors

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients with known or suspected coronary artery disease may have increased risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT1 agonists may cause coronary vasospasm)

Almotriptan (Axert)

Used to treat acute migraine. Selective 5-HT_1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.

Dosing

Adult

6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP450-3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity

Contraindications

Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Decrease dose and do not exceed 12.5 mg/d in renal or hepatic impairment

Rizatriptan (Maxalt, Maxalt-MLT)

Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.

Dosing

Adult

5-10 mg PO q2h prn for headache; not to exceed 30 mg/d

Pediatric

Not established

Interactions

Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur when administering this medication

Combination antimigraine drugs

These agents are useful in aborting acute migraine attacks. The first combination product of a 5-HT1 receptor agonist and an NSAID, Treximet, was approved by the US Food and Drug Administration in April 2008. Efficacy was demonstrated in 2 randomized, double-blind, multicenter, parallel-group trials comparing the combination product to placebo and each individual active component (ie, sumatriptan and naproxen sodium). The percentage of patients remaining pain free without use of other medications through 24 hours postdose was significantly greater (p<0.01) among patients receiving a single dose of Treximet (25% and 23%) compared with placebo (8% and 7%) or either sumatriptan (16% and 14%) or naproxen sodium (10%) alone.⁶

Sumatriptan and naproxen (Treximet)

Combination product containing sumatriptan, a selective 5-hydroxytryptamine (5-HT₁) receptor agonist, and naproxen sodium, an arylacetic acid nonsteroidal anti-inflammatory drug (NSAID). Fixed combination contains sumatriptan 85 mg and naproxen sodium 500 mg. Indicated for acute migraine. Sumatriptan mediates vasoconstriction of the basilar artery and vasculature of dura mater, which correlates with migraine relief. Naproxen provides analgesic, anti-inflammatory, and antipyretic properties. Decreases activity of cyclooxygenase, thereby interrupting prostaglandin synthesis.

Dosing

Adult

1 tab PO at onset of migraine; do not exceed 2 tab/24 h; if second dose administered, do not administer until at least 2 h after first dose

Pediatric

Not established

Interactions

Do not split, crush, or chew tab
Sumatriptan: Do not administer within 24 h of ergotamine-containing or ergot-type drugs (eg, dihydroergotamine, methysergide); coadministration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase risk for serotonin syndrome; coadministration with MAOIs or within 2 wk of discontinuing MAOIs may increase sumatriptan levels (see Contraindications)
Naproxen: Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Contraindications

Documented hypersensitivity; ischemic heart disease (eg, stable angina, vasospastic forms of angina, myocardial infarction, silent myocardial ischemia); uncontrolled hypertension; cerebrovascular or peripheral vascular disease; history of coronary artery bypass graft (CABG) surgery; peptic ulcer disease; recent GI bleeding or perforation; renal (CrCl <30 mL/min) or hepatic insufficiency; coadministration with MAOIs or within 2 wk of discontinuing MAOI; hemiplegic or basilar migraine; patients in whom aspirin or other NSAIDs induce asthma, rhinitis, nasal polyps, or urticaria

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Sumatriptan may increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke
Naproxen may increase risk of serious GI adverse events (eg, bleeding, ulceration, stomach or intestinal perforation); acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug; preexisting asthma

Isometheptene dichloralphenazone acetaminophen (Midrin)

Has sympathomimetic properties. Dilates cranial and cerebral arterioles, causing reduction in stimuli that lead to vascular headaches.

Dosing

Adult

2 cap PO at once followed by 1 cap q1h until satisfactory response obtained; not to exceed 5 cap/12 h

Pediatric

Not established

Interactions

Concurrent MAOIs may result in severe headache, hypertension, and hyperpyrexia, which, in turn, may result in hypertensive crisis

Contraindications

Documented hypersensitivity; glaucoma; hypertension; organic heart disease; severe renal disease; hepatic disease; MAOI within last 2 wk

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension, peripheral vascular disease, and recent cardiovascular injuries

Ergot alkaloids and derivatives

These are direct vasoconstrictors of smooth muscle in cranial blood vessels. Their activity depends on the CNS vascular tone at the time of administration.

Ergotamine tartrate (Cafergot, Cafatine, Cafetrate)

Has alpha-adrenergic antagonist and serotonin antagonist effects. Causes constriction of peripheral and cranial blood vessels.

Dosing

Adult

2 tab PO at onset of attack, 1 tab q30min prn; not to exceed 6 tab per attack or 10 tab/wk
1 tab SL at first sign of attack and 1 tab q30min; not to exceed 3 tab/d or 5 tab/wk
1 supp PR at first sign of attack with second dose after 1 h prn; not to exceed 2 supp/attack or 5 supp/wk

Pediatric

Not established

Interactions

Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin

Contraindications

Documented hypersensitivity; hepatic or renal disease; peptic ulcer disease; sepsis; peripheral vascular disease

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Avoid using prolonged regimens because of danger of causing gangrene or dependency

Dihydroergotamine (D.H.E. 45, Migranal Nasal Spray)

More effective when given early in migraine attack. Has alpha-adrenergic antagonist and serotonin antagonist effects.

Dosing

Adult

1 mg IM at first sign of headache, repeat q1h; not to exceed 3 mg total dose
2 mg IV maximum dose for faster effects; most commonly given at 0.5-1 mg IV with antiemetic; not to exceed 6 mg/wk
Intranasal: 1 spray into each nostril and repeat prn within 15 min; not to exceed 6 sprays/d or 8 sprays/wk

Pediatric

Not established

Interactions

Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin

Contraindications

Documented hypersensitivity; sumatriptan or zolmitriptan within last 24 h; MAOIs in last 2 wk

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease

Barbiturates

These agents are used in combination with aspirin and acetaminophen for pain relief and to induce sleep. Caffeine is also used to increase GI absorption. However, butalbital and narcotics are associated with rebound headaches. Increasing the use of combination preparations may fail to provide pain relief and worsen headache symptoms.

Acetaminophen/butalbital/caffeine (Fioricet)

Drug combination used to relieve tension headaches. Barbiturate component has generalized depressant effect on CNS.

Dosing

Adult

1-2 tab or cap PO q4h; not to exceed 6 tab or cap/d

Pediatric

Not established

Interactions

Effects decreased by phenothiazines, quinidine, tricyclic antidepressants, theophylline, haloperidol, chloramphenicol, ethosuximide, corticosteroids, warfarin, doxycycline, and beta-blockers; effects increased by CNS depressants, methylphenidate, valproic acid, propoxyphene, and benzodiazepines

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Risk of rebound headache and overuse; caution in patients with history of substance abuse

Aspirin/butalbital/caffeine (Fiorinal)

Drug combination used to relieve tension headaches. Barbiturate component has generalized depressant effect on CNS.

Dosing

Adult

1-2 tab or cap PO q4h; not to exceed 6 tab or cap/d

Pediatric

Not established

Interactions

Effects decreased by phenothiazines, quinidine, tricyclic antidepressants, theophylline, haloperidol, chloramphenicol, ethosuximide, corticosteroids, warfarin, doxycycline, and beta-blockers; effects increased by CNS depressants, methylphenidate, valproic acid, propoxyphene, and benzodiazepines

Contraindications

Documented hypersensitivity; children or adolescents experiencing flulike symptoms or chickenpox

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Risk of rebound headache and overuse; caution in patients with history of substance abuse

Antiemetics

These agents are used to treat migraine and the emesis associated with acute attacks.

Prochlorperazine (Compazine)

Antidopaminergic drug that blocks postsynaptic mesolimbic dopamine receptors, has an anticholinergic effect, and can depress reticular activating system, possible mechanism for relieving nausea and vomiting.

Dosing

Adult

5-10 mg PO/IM tid/qid; not to exceed 40 mg/d
2.5-10 mg IV q3-4h prn (most common route given in ED); not to exceed 10 mg/dose or 40 mg/d
25 mg PR bid

Pediatric

2.5 mg PO/PR q8h or 5 mg q12h prn; not to exceed 15 mg/d IV not recommended for children
0.1-0.15 mg/kg/dose IM; change to PO as soon as possible

Interactions

Coadministration with other CNS depressants or anticonvulsants may cause additive effects; with epinephrine may cause hypotension

Contraindications

Documented hypersensitivity; bone marrow suppression; narrow-angle glaucoma; severe liver or cardiac disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Drug-induced Parkinson syndrome or pseudoparkinsonism occurs quite frequently; akathisia most common extrapyramidal reaction in elderly; lowers seizure threshold; caution with history of seizures

Promethazine (Phenergan)

Phenothiazine derivative that possesses antihistaminic, sedative, antimotion sickness, antiemetic, and anticholinergic effects.

Dosing

Adult

12.5 mg PO/PR tid and 25 mg hs
25 mg IV/IM, repeat prn in 2 h; switch to PO as soon as possible

Pediatric

<2 years: Contraindicated
>2 years: 0.25-1 mg/kg PO/IV/IM/PR q4-6h prn

Interactions

May have additive effects with other CNS depressants or anticonvulsants; with epinephrine may cause hypotension

Contraindications

Documented hypersensitivity; children younger than 2 y (incidences of death due to respiratory depression)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, impaired liver function, seizures, sleep apnea, and asthma

Metoclopramide (Reglan)

Indicated for migraine-associated nausea. Works by blocking dopamine receptors in the chemoreceptor trigger zone of the CNS. Can be used as an alternative to prochlorperazine. Studies have shown that prochlorperazine is better.

Dosing

Adult

5-10 mg PO or 5-20 mg IV/IM tid

Pediatric

Not established

Interactions

Anticholinergic agents may antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS

Contraindications

Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction or perforation; history of seizure disorders

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in history of mental illness and Parkinson disease

Droperidol (Inapsine)

Neuroleptic agent that may reduce emesis by blocking dopamine stimulation of chemoreceptor trigger zone.

Dosing

Adult

2.5-10 mg IV/IM q3-4h prn (2.5 mg for headache)

Pediatric

<2 years: Not established
2-12 years: 0.088-0.165 mg/kg IV/IM prn
>12 years: Administer as in adults

Interactions

May increase toxicity of CNS depressants

Contraindications

Documented hypersensitivity; prolonged QT interval

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypovolemic patients may experience hypotension; droperidol may decrease pulmonary arterial pressure; tardive dyskinesia in patients receiving droperidol is 40%; elderly persons may experience high rate of extrapyramidal reactions; life-threatening arrhythmias may occur in patients receiving this medication (for droperidol, the black box warning: potentially fatal QT prolongation; many institutions recommend an ECG or rhythm strip to look for QT prolongation before administering)

Follow-up

Further Outpatient Care

• Avoid precipitants of attacks, if possible.
• Follow-up with primary care physician and neurologist after first or subsequent attacks.
  

Inpatient & Outpatient Medications

• Multitude of drugs used for migraine prophylaxis
  • Beta-blockers: Atenolol, propranolol, timolol
  • Antidepressants: Amitriptyline (Elavil), nortriptyline (Pamelor)
  • Ergot derivatives: Methysergide (Sansert)
  • Antihistamines: Cyproheptadine (Periactin)
  • Anticonvulsants: Valproic acid (Depakene, Depakote)
• Abortive therapies
  • Alpha2-adrenergic receptor agonists (Clonidine)
  • Calcium channel blockers: Nimodipine, nifedipine, verapamil
  • NSAIDs

Patient Education

• For excellent patient education resources, see eMedicine's Headache Center. Also, visit eMedicine's patient education articles Causes and Treatments of Migraine and Related Headaches, Migraine Headache, Alternative and Complementary Approaches to Migraine and Cluster Headaches, Migraine Headache FAQs, and Understanding Migraine and Cluster Headache Medications.
• For more information, see Medscape's Headache Resource Center.

Miscellaneous

Medicolegal Pitfalls

• Must rule out other potentially life-threatening forms of headache (eg, subarachnoid hemorrhage, meningitis).

References

1. [Guideline] Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9-160. [Medline].

2. {Guideline} Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care setting: Pharmacological management of acute attacks. American Academy of Neurology. Available at http://www.aan.com. Accessed October 31, 2007.

3. [Guideline] Solomon GD, Cady RK, Klapper JA, Ryan RE Jr. Standards of care for treating headache in primary care practice. National Headache Foundation. Cleve Clin J Med. Jul-Aug 1997;64(7):373-83. [Medline].

4. [Guideline] Ducharme J. Canadian Association of Emergency Physicians Guidelines for the acute management of migraine headache. J Emerg Med. Jan-Feb 1999;17(1):137-44. [Medline].

5. Cutrer FM, Charles A. The neurogenic basis of migraine. Headache. Oct 2008;48(9):1411-4. [Medline].

6. [Best Evidence] Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. Apr 4 2007;297(13):1443-54. [Medline].

7. Bussone G, Grazzi L, D'Amico D, et al. Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac- K/Sumatriptan Migraine Study Group. Cephalalgia. May 1999;19(4):232-40. [Medline].

8. Cady R. Migraine. In: Five Minute Clinical Consult. 1997:676-77.

9. Caesar R. Acute headache management: the challenge of deciphering etiologies to guide assessment and treatment. Emerg Med Rep. 1995;16(13):117-28.

10. Capobianco DJ, Cheshire WP, Campbell JK. An overview of the diagnosis and pharmacologic treatment of migraine. Mayo Clin Proc. Nov 1996;71(11):1055-66. [Medline].

11. Diener HC, Kaube H, Limmroth V. A practical guide to the management and prevention of migraine. Drugs. Nov 1998;56(5):811-24. [Medline].

12. Evans RW. Diagnostic testing for the evaluation of headaches. Neurol Clin. Feb 1996;14(1):1-26. [Medline].

13. Henry GL. Headache. In: Emergency Medicine Concepts and Clinical Practice. 3^rd ed. 1992:1751-66.

14. Hoffman GL. Headache and facial pain. In: Emergency Medicine. 4^th ed. 1996:chap192/1008-14.

15. Lance JW. Current concepts of migraine pathogenesis. Neurology. Jun 1993;43(6 Suppl 3):S11-5. [Medline].

16. [Guideline] Members of the task force; Evers S, Afra J, Frese A, Goadsby PJ, Linde M. EFNS guideline on the drug treatment of migraine - report of an EFNS task force. Eur J Neurol. Jun 2006;13(6):560-72. [Medline].

17. Ramirez-Lassepas M, Espinosa CE, Cicero JJ, et al. Predictors of intracranial pathologic findings in patients who seek emergency care because of headache. Arch Neurol. Dec 1997;54(12):1506-9. [Medline].

18. Saper JR. Diagnosis and symptomatic treatment of migraine. Headache. 1997;37 Suppl 1:S1-14. [Medline].

19. Sheftell FD, Tepper SJ. New paradigms in the recognition and acute treatment of migraine. Headache. Jan 2002;42(1):58-69. [Medline].

20. Silberstein SD. Evaluation and emergency treatment of headache. Headache. Sep 1992;32(8):396-407. [Medline].

21. Silberstein SD. Recent developments in migraine. Lancet. Oct 18 2008;372(9647):1369-71. [Medline].

22. Stewart WF, Lipton RB, Celentano DD, et al. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. Jan 1 1992;267(1):64-9. [Medline].

23. Stewart WF, Shechter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology. Jun 1994;44(6 Suppl 4):S17-23. [Medline].

24. Tfelt-Hansen P. Efficacy and adverse events of subcutaneous, oral, and intranasal sumatriptan used for migraine treatment: a systematic review based on number needed to treat. Cephalalgia. Oct 1998;18(8):532-8. [Medline].

25. Thomas SH, Stone CK. Emergency department treatment of migraine, tension, and mixed-type headache. J Emerg Med. Sep-Oct 1994;12(5):657-64. [Medline].

26. Thomas SH, Stone CK, Ray VG, et al. Intravenous versus rectal prochlorperazine in the treatment of benign vascular or tension headache: a randomized, prospective, double-blind trial. Ann Emerg Med. Nov 1994;24(5):923-7. [Medline].

Keywords

migraine, migraine headache, headache, migraine variant, classic migraine, cluster headache, aura, dizziness, tinnitus, scotomas, photophobia, visual scintillations, bright zigzag lines, migraine with aura, migraine without aura, dopamine receptor hypersensitivity, visual aura, fortification spectra, geometric visual patterns, hemianopsia, blind spots, hallucinations, hemicrania,throbbingheadache, pulsatile headache, lightheadedness, phonophobia, Valsalva maneuvers, hemiplegic migraine, aphasia, third nerve palsy, ophthalmoplegic migraine, ocular muscle paralysis, ptosis, alcohol consumption, fatigue, emotional stress, birth control pills, vasodilators

Contributor Information and Disclosures

Author

Michelle Blanda, MD, Chair, Department of Emergency Medicine, Summa Health System; 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
Disclosure: Nothing to disclose.

Coauthor(s)

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
Disclosure: Nothing to disclose.

Medical Editor

Edward A Michelson, MD, Program Director, Associate Professor, Department of Emergency Medicine, University Hospital Health Systems in 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
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
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
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA 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
Disclosure: Nothing to disclose.

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