Headache, Migraine

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. 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.

Pathophysiology
The pathophysiology of migraine headaches is not clearly understood. Growing evidence supports the role of neurogenic peptides, such as serotonin and dopamine, in the brain. 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.

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

DIFFERENTIALS
Other Problems to be Considered
Brain tumor (increased intracranial pressure) Opiate dependance/opiate withdrawal headache Pseudotumor cerebri Vascular pathology (eg, aneurysm)
WORKUP

Lab 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.
Drug Category: Analgesics
Initial therapy for patients with infrequent migraines can be simple analgesics.
Drug Name
Acetaminophen and codeine (Tylenol #3)
Description
Drug combination indicated for treatment of mild to moderately severe headache.Note: Some patients may respond to maximal acetaminophen alone, without codeine.
Adult Dose
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 Dose
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
Contraindications
Documented hypersensitivity
Interactions
CNS depressants or tricyclic antidepressants increase toxicity
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
Drug Name
Acetaminophen (Tylenol, Aspirin Free Anacin, Panadol)
Description
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.
Adult Dose
325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric Dose
<12>12 years: 325-650 mg PO q4h; not to exceed 5 doses in 24 h
Contraindications
Documented hypersensitivity; G-6-PD deficiency
Interactions
Rifampin can reduce analgesic effects; barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
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
Drug Name
Aspirin (Anacin, Ascriptin, Bayer Aspirin)
Description
May alleviate migraine attacks by inhibiting prostaglandin synthesis. Mild migraines usually respond well to this medication.
Adult Dose
325-650 mg PO q4-6h prn; not to exceed 4 g/d
Pediatric Dose
10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
Contraindications
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthmaBecause of association with Reye syndrome, do not use in children (<16>2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetusD - 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
Drug Category: 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.
Drug Name
Naproxen (Anaprox, Naprelan, Naprosyn)
Description
Used for relief of mild to moderately severe headaches. Inhibits inflammatory reactions and pain by decreasing activity of enzyme cyclooxygenase, thus inhibiting prostaglandin synthesis.
Adult Dose
500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric Dose
<2>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Contraindications
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
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
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetusD - 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
Drug Name
Ketoprofen (Oruvail, Orudis, Actron)
Description
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.
Adult Dose
25-50 mg PO q6-8h prn; not to exceed 300 mg/d
Pediatric Dose
<3>12 years: Administer as in adults
Contraindications
Documented hypersensitivity
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
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetusD - 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
Drug Name
Ketorolac (Toradol)
Description
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.
Adult Dose
30 mg IV single dose (most common route used in ED)>65 years, renal impairment, or body weight <50>2 years: 0.25-1 mg/kg PO/IV/IM/PR q4-6h prn
Contraindications
Documented hypersensitivity; children younger than 2 y (incidences of death due to respiratory depression)
Interactions
May have additive effects with other CNS depressants or anticonvulsants; with epinephrine may cause hypotension
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
Drug Name
Metoclopramide (Reglan)
Description
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.
Adult Dose
5-10 mg PO or 5-20 mg IV/IM tid
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; pheochromocytoma or GI hemorrhage, obstruction or perforation; history of seizure disorders
Interactions
Anticholinergic agents may antagonize effects of metoclopramide; opiate analgesics may increase metoclopramide toxicity in CNS
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
Drug Name
Droperidol (Inapsine)
Description
Neuroleptic agent that may reduce emesis by blocking dopamine stimulation of chemoreceptor trigger zone.
Adult Dose
2.5-10 mg IV/IM q3-4h prn (2.5 mg for headache)
Pediatric Dose
<2>12 years: Administer as in adults
Contraindications
Documented hypersensitivity; prolonged QT interval
Interactions
May increase toxicity of CNS depressants
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)
Drug Category: 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.
Drug Name
Ergotamine tartrate (Cafergot, Cafatine, Cafetrate)
Description
Has alpha-adrenergic antagonist and serotonin antagonist effects. Causes constriction of peripheral and cranial blood vessels.
Adult Dose
2 tab PO at onset of attack, 1 tab q30min prn; not to exceed 6 tab per attack or 10 tab/wk1 tab SL at first sign of attack and 1 tab q30min; not to exceed 3 tab/d or 5 tab/wk1 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 Dose
Not established
Contraindications
Documented hypersensitivity; hepatic or renal disease; peptic ulcer disease; sepsis; peripheral vascular disease
Interactions
Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Avoid using prolonged regimens because of danger of causing gangrene or dependency
Drug Name
Dihydroergotamine (D.H.E. 45, Migranal Nasal Spray)
Description
More effective when given early in migraine attack. Has alpha-adrenergic antagonist and serotonin antagonist effects.
Adult Dose
1 mg IM at first sign of headache, repeat q1h; not to exceed 3 mg total dose2 mg IV maximum dose for faster effects; most commonly given at 0.5-1 mg IV with antiemetic; not to exceed 6 mg/wkIntranasal: 1 spray into each nostril and repeat prn within 15 min; not to exceed 6 sprays/d or 8 sprays/wk
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; sumatriptan or zolmitriptan within last 24 h; MAOIs in last 2 wk
Interactions
Increases effects of heparin; increases toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Caution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease
Drug Category: 5- HT1 Serotonin receptor agonist
The stimulation of 5-HT1 receptors produce a direct vasoconstrictive effect.
Drug Name
Sumatriptan (Imitrex)
Description
Selective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.
Adult Dose
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/d6 mg SC; if satisfactory response not observed in 1 h, an additional 6 mg SC may be administered; not to exceed 2 injections/dIntranasal: 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 Dose
Not established
Contraindications
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; coadministration or within 2 wk of MAOIs
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
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 rarelyPatients 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)
Drug Name
Zolmitriptan (Zomig, Zomig-ZMT)
Description
Selective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.
Adult Dose
2.5 mg or 5 mg PO; repeat dose after 2 h prn; not to exceed 10 mg/d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; another serotonin agonist or ergotamine within last 24 h; MAOI within last 2 wk
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
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 occurDecrease dose of almotriptan and do not exceed 12.5 mg/d in renal or hepatic impairment
Drug Name
Frovatriptan (Frova)
Description
Used to treat acute migraine. Selective 5-HT1B/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.
Adult Dose
2.5 mg PO once at onset of migraine attack
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
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
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
Drug Name
Eletriptan (Relpax)
Description
Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine.
Adult Dose
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 Dose
<18>65 y; administration within 72 h of potent CYP450 3A4 inhibitors
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
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)
Drug Name
Almotriptan (Axert)
Description
Used to treat acute migraine. Selective 5-HT1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.
Adult Dose
6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
Pediatric Dose
<18>18 years: Administer as in adults
Contraindications
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
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
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
Drug Name
Rizatriptan (Maxalt, Maxalt-MLT)
Description
Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.
Adult Dose
5-10 mg PO q2h prn for headache; not to exceed 30 mg/d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
Interactions
Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs
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
Drug Category: Combination antimigraine drugs
These agents are useful in aborting migraine attacks.
Drug Name
Isometheptene dichloralphenazone acetaminophen (Midrin)
Description
Has sympathomimetic properties. Dilates cranial and cerebral arterioles, causing reduction in stimuli that lead to vascular headaches.
Adult Dose
2 cap PO at once followed by 1 cap q1h until satisfactory response obtained; not to exceed 5 cap/12 h
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; glaucoma; hypertension; organic heart disease; severe renal disease; hepatic disease; MAOI within last 2 wk
Interactions
Concurrent MAOIs may result in severe headache, hypertension, and hyperpyrexia, which, in turn, may result in hypertensive crisis
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
Drug Category: 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.
Drug Name
Acetaminophen/butalbital/caffeine (Fioricet)
Description
Drug combination used to relieve tension headaches. Barbiturate component has generalized depressant effect on CNS.
Adult Dose
1-2 tab or cap PO q4h; not to exceed 6 tab or cap/d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity
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
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
Drug Name
Aspirin/butalbital/caffeine (Fiorinal)
Description
Drug combination used to relieve tension headaches. Barbiturate component has generalized depressant effect on CNS.
Adult Dose
1-2 tab or cap PO q4h; not to exceed 6 tab or cap/d
Pediatric Dose
Not established
Contraindications
Documented hypersensitivity; children or adolescents experiencing flulike symptoms or chickenpox
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
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

FOLLOW-UP
Further Outpatient Care
Avoid precipitants of attacks, if possible.
Follow-up with primary care physician and neurologist after first or subsequent attacks.

In/Out Patient Meds
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
Medical/Legal Pitfalls
Must rule out other potentially life-threatening forms of headache (eg, subarachnoid hemorrhage, meningitis).

REFERENCES
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Headache, Migraine excerpt
Article Last Updated: Jan 3, 2008