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Author: Ronald Braswell, MD, Assistant Professor, Department of Ophthalmology, University of Alabama-Birmingham

Ronald Braswell is a member of the following medical societies: American Academy of Ophthalmology and North American Neuro-Ophthalmology Society

Editors: Eric R Eggenberger, DO, MS, Vice-Chairman, Professor, Department of Neurology and Ophthalmology, Michigan State University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Jane W Chan, MD, Associate Professor of Neurology/Ophthalmology, Departments of Neurology and Ophthalmology, University of Kentucky College of Medicine; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Robert A Egan, MD, Director of Neuro-Ophthalmology, St Helena Hospital

Author and Editor Disclosure

Synonyms and related keywords: complex migraines, migraine equivalent, migraine variant, classic migraine, cluster headache, aura, ophthalmoplegic migraine, retinal migraine, migrainous disorder, 5-hydroxytryptamine, 5-HT, dihydroergotamine, DHE, migraine headache, headache disorder

Background

This complex, recurrent headache disorder is one of the most common complaints in medicine today. The term migraine is derived from the Greek word hemikrania. This later was corrupted into low Latin as hemigranea, which eventually was accepted by the French translation as migraine. A typical episode is characterized by unilateral head pain that may be preceded by various prodromal symptoms. Other focal neurological symptoms, collectively known as an aura, may precede or coincide with the onset of headache. Although many more headache types are listed in the International Classification of Headache Disorders1, the following are the most often encountered in practice, with migraine being the most challenging:

  • Migraine without aura (formerly common migraine)
  • Probable migraine without aura
  • Migraine with aura (formerly classic migraine)
  • Probable migraine with aura
  • Chronic migraine
  • Chronic migraine associated with analgesic overuse
  • Tension-type headache
  • Cluster headache
  • Chronic daily headache
  • Ophthalmoplegic migraine
  • Retinal migraine
  • Childhood periodic syndromes that may not be precursors to or associated with migraine
  • Complications of migraine
  • Migrainous disorder not fulfilling above criteria

Pathophysiology

Historically, migraine has been associated with fluctuations in cerebral perfusion. Investigations show areas of hypoperfusion preceding the onset of headache, followed by a period of reactive hyperperfusion and eventual normalization of flow. Current theories advocate a primarily neurogenic phenomenon related to changes in levels of neuropeptides serotonin and dopamine.

  • Certain symptomatic and prophylactic agents are effective (in part) through binding at specific serotonin (5-hydroxytryptamine [5-HT]) binding sites.
  • Signs and symptoms (eg, anorexia, nausea, vomiting, pallor, yawning) respond to dopaminergic antagonists.
  • The concept of an altered migrainous threshold in individual patients has been advocated. Imbalances in inhibitory and excitatory neuronal pathways may sensitize the trigeminovascular system and provoke a migraine event.

Frequency

United States

Recent epidemiological studies indicate that 23 million Americans, approximately 18% of females and 6% of males, have one or more migraine headaches per year.

Migraine headaches are experienced by 64% of all female and 43% of all male sufferers of severe headache.

Mortality/Morbidity

Migraine headache continues to be a major health problem.

  • In the American Migraine Study, more then 85% of women and 82% of men with severe migraine had headache-related disability.
  • Estimated lost productivity is $1-13 billion dollars per year.
  • Migraineur males required 3.8 bedrest days per year; women, 5.6 days.

Race

  • A recent study showed that among women, 20.4% of whites, 16.2% of African Americans, and only 9.2% of Asian Americans met IHS criteria for migraine.
  • Similarly, in males, 8.6% of whites, 7.2% of African Americans, and 4.8% of Asian Americans were considered to have migraine.

Sex

In children younger than 10 years, prevalence appears to be higher in males than in females. After the onset of puberty, migraine is considerably more common in females (female-to-male ratio 3:1).

  • In general, the incidence of migraine in males declines to a low rate by age 28-29 years (1 case per 1000 person-years).
  • For females, the incidence of migraine with aura peaks at age 12-13 years (3-4 y before that of migraine without aura).
  • Migraine prevalence among females increases sharply up to age 40 years and then declines gradually. The male peak prevalence is slightly less and decreases over a broader age range.

Age

  • Incidence or age of onset of migraine with aura appears to peak at or before age 4-5 years (6.6 cases per 1000 person-years), whereas the highest incidence for migraine without aura occurs at age 10-11 years (10.1 cases per 1000 person-years).
  • Data indicate that migraine is a chronic condition, although prolonged remissions are common. One study showed that 62% of young adults were migraine free for more than 2 years, but only 40% continued to be migraine free after 30 years.
  • The severity and frequency of attacks tend to diminish with increasing age. After 15 years, approximately 30% of men and 40% of women no longer have migraine attacks.



History

The migraine headache is typically a unilateral and throbbing pain, but the features often vary. Migraineurs often experience a bilateral event. The pain can be felt anywhere around the head or neck.

  • Prodrome is experienced by 60% of patients.
    • Forewarning of a migraine may occur hours to days before a headache event.
    • Although the specific features of the prodrome vary, they tend to be consistent for a given individual. They may include the following:
      • Neurological symptoms (eg, photophobia, phonophobia, osmophobia)
      • Lethargy
      • Mental and mood changes (eg, depression, anger, euphoria)
      • Polyuria
      • Meningismus
      • Anorexia
      • Constipation or diarrhea
  • Aura is experienced by 10-20% of patients.
    • Aura is defined as focal neurological symptoms that evolve over a period of 5-15 minutes and generally last approximately 1 hour.
    • In most cases, the headache follows the aura. However, the 2 events can occur simultaneously, or the aura may develop after the headache is in progress.
    • Visual symptoms, including the following, are most common:
      • Negative scotomata or negative visual phenomena, such as homonymous hemianopic or quadrantic field defects, central scotomata, tunnel vision, altitudinal visual defects, or even complete blindness
      • Positive visual phenomena or scintillating scotomata, the most common consisting of an absent arc or band of vision with a shimmering or glittering zigzag border: This often is combined with photopsias or visual hallucinations, which may take various shapes. This is a highly characteristic syndrome that always occurs prior to the headache phase of an attack and is pathognomonic of a classic migraine. It is called a "fortification spectrum" because the serrated edges of the hallucinated "C" resemble a "fortified town with bastions around it."
      • Photophobia
      • Photopsia (uniform flashes of light) or simple forms of visual hallucinations that occur commonly with positive visual phenomena
  • Motor symptoms may be observed.
    • Hemiparesis
    • Aphasia
  • Headache characteristics typically include the following:
    • Unilateral (60-70%)
    • Gradual onset, lasting 4-72 hours
    • Described as a throbbing or pulsatile type of pain but can evolve into a chronic ache or bandlike pattern
  • Associated symptoms include the following:
    • Anorexia
    • Nausea
    • Vomiting
    • Blurred vision
    • Skin pallor
    • Photophobia
    • Phonophobia
    • Light-headedness

Physical

Evidence of autonomic nervous system involvement can be helpful, although most patients with migraine exhibit few or no findings. Serial neurologic examinations are recommended.

  • Possible findings
    • Cranial/cervical muscle tenderness
    • Horner syndrome (ie, relative miosis with 1-2 mm of ptosis on the same side as the headache)
    • Conjunctival injection
    • Tachycardia/bradycardia
    • Hypertension/hypotension
    • Hemisensory or hemiparetic neurological deficits (ie, complicated migraine)
    • Adie type pupil (ie, poor light reactivity with light-near dissociation)
  • Pertinent physical examination negatives
    • Dim scotoma lasting a few seconds to several minutes (ie, amaurosis)
    • Temporal artery tenderness in the elderly
    • Meningismus
    • Increased lethargy (unrelated to medication use)
    • Mental status changes

Causes

No specific etiology is known. Various precipitants of migraine events have been identified.

  • Family history
  • Stress
  • Excessive or insufficient sleep
  • Medications - Vasodilators, oral contraceptives
  • Smoking
  • Foods and food additives - Alcohol, caffeine, chocolate, artificial sweeteners (aspartame, saccharin), monosodium glutamate (MSG), citrus fruits, meats with nitrites, salt
  • Foods containing tyramines - Aged cheese, yogurt, sour cream, chicken livers, sausages, bananas, avocados, canned figs, raisins, peanuts, soy sauce, pickled fish, fresh-baked breads, pork, vinegars, beans
  • Exposure to bright or fluorescent lighting
  • Strong odors (eg, perfumes, colognes, petroleum distillates)
  • Hormonal changes - Menstruation (common association), pregnancy, ovulation
  • Head trauma
  • Weather changes
  • Metabolic or infectious diseases
  • Physical exertion or fatigue
  • Motion sickness
  • Cold stimulus (ice cream headaches)



Arteriovenous Malformations
Aseptic Meningitis
Cavernous Sinus Syndromes
Cerebral Aneurysms
Cluster Headache
Complex Partial Seizures
Dissection Syndromes
Headache: Pediatric Perspective
Intracranial Hemorrhage
Migraine Headache
Migraine Headache: Pediatric Perspective
Migraine Variants
Muscle Contraction Tension Headache
Neurosarcoidosis
Pathophysiology and Treatment of Migraine and Related Headache
Persistent Idiopathic Facial Pain
Pseudotumor Cerebri
Temporal/Giant Cell Arteritis
Temporomandibular Disorders
Tolosa-Hunt Syndrome
Trigeminal Neuralgia
Viral Meningitis

Other Problems to be Considered

Transient Ischemic attacks/amaurosis fugax
Adie pupil
Horner syndrome
Angle-closure glaucoma
Physiologic anisocoria
Sinusitis
Drug-seeking behavior
Sarcoidosis
Idiopathic intracranial hypertension



Lab Studies

  • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be necessary in the appropriate age group to rule out giant cell arteritis. Other causes should be ruled out using appropriate laboratory and/or radiographic tests.
  • Migraine is a diagnosis of exclusion. The clinician should have a heightened sense of concern in patients with solely unilateral headaches.

Imaging Studies

  • Head CT scan to rule out intracerebral hemorrhage, ischemic stroke, or previous head trauma
  • Head MRI/MRA (magnetic resonance angiogram) to rule out a mass lesion or vascular anomaly (aneurysm or arteriovenous malformation)
  • CT angiogram is another excellent choice for evaluating intracranial vascular lesions.

Other Tests

  • Visual field testing should be performed in patients with persistent visual phenomena.

Procedures

  • Lumbar puncture to rule out infection, inflammation, elevated intracranial pressure, or subarachnoid hemorrhage
  • Temporal artery biopsy when clinically appropriate



Medical Care

  • After making the appropriate diagnosis, the physician should counsel patients about nonpharmacologic treatments: regular rest, good sleep hygiene, and exercise.
  • Patients should avoid potential triggering factors.
    • Patients may need to discontinue any medications that exacerbate the headache.
    • If oral contraceptives or hormonal replacement therapy is suspected to be a potential trigger mechanism, reduce dosages, if possible.
    • Consider discontinuing hormone therapy, if headaches persist.
  • Intramuscular injections of botulinum toxin (BOTOX®) around the scalp have proven to be an effective treatment in some patients.

Consultations

Neurologist, neuro-ophthalmologist, and/or neurosurgeon should be consulted as deemed clinically appropriate.

Diet

Avoid dietary triggers of migraine.

Activity

Patients should exercise and/or sleep as needed.



Pharmacologic therapy is directed primarily at alleviating the acute phase. Repeated episodes of migraine may require long-term prophylactic therapy.

See more on New Developments in Headache Diagnosis and Management

Drug Category: 5-HT1 receptor agonists

These agents are used for acute treatment of migraine.

Eletriptan (Relpax) has recently been approved for use in the United States. It is also a selective serotonin agonist and 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. The adult dose is 20-40 mg PO at onset of migraine; and, if the initial dose is ineffective, dose may be repeated once after 2 h. Use in children <18 y is not established. The total daily dose should not exceed 80 mg.

Drug interactions include potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), which may increase toxicity, and concurrent administration with ergot-containing drugs, which may increase vasospastic reactions. In patients with known or suspected coronary artery disease, eletriptan (similar to other serotonin agonists) may increase risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT1 agonists may cause coronary vasospasm).

Drug NameSumatriptan (Imitrex), frovatriptan (Frova), eletriptan (Relpax), naratriptan (Amerge, Naramig)
DescriptionVascular 5-HT1 receptor subtypes (to which these agents bind selectively and through which they presumably exert antimigrainous effects) have been shown to be excellent first-line therapy for acute migraine events. Naratriptan has a duration of action of up to 24 h with low headache recurrence rate. Useful for patients with slow onset, prolonged migraine (eg, menstrual migraine). Frovatriptan possesses long half-life (ie, 26-30 h), decreasing recurrence of migraine within 24 h after treatment. Eletriptan has half-life of 18 h.
Adult DoseSumatriptan: 6 mg SC injection; if no response, repeat after 1 h; not to exceed 2 doses in 24 h
25-100 mg PO single dose; repeat at intervals of at least 2 h; not to exceed 200 mg/d (100 mg/d if injection)
5-20 mg intranasally; reevaluate if no response; may repeat once after 2 h; not to exceed 40 mg/d
Frovatriptan: 2.5 mg PO once at onset of migraine attack
Eletriptan: 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
Naratriptan: 1-2.5 mg PO initially PO q4h; not to exceed 5 mg/d
Pediatric DoseNot recommended
ContraindicationsDocumented ischemic cardiac, cerebrovascular, or peripheral vascular syndromes; vasospastic coronary artery disease; uncontrolled hypertension; basilar or hemiplegic migraine; within 24 h of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists; during or within 2 wk after discontinuing MAOIs
InteractionsToxicity 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
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsConfirm diagnosis; avoid excessive use; exclude underlying cardiovascular disease, supervise first dose, and consider monitoring ECG in patients with a likelihood of unrecognized coronary artery disease (eg, postmenopausal women, those with hypercholesterolemia, men >40 y, patients with hypertension, those with a strong family history, and patients who are obese, diabetic, or smoke); hepatic or renal dysfunction

Drug NameZolmitriptan (Zomig, Zomig-ZMT), almotriptan (Axert), rizatriptan (Maxalt, Maxalt-MLT)
DescriptionSelective agonist for serotonin 5-HT1 receptors in cranial arteries. Suppresses inflammation associated with migraine headaches.
Adult DoseZolmitriptan: 2.5 mg PO initially; repeat dose after 2 h if headache returns; not to exceed 10 mg/24 h
Almotriptan: 6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
Rizatriptan: 5-10 mg intranasally initially; repeat after 2 h; not to exceed 30 mg/d; concomitant administration of 5 mg/dose PO propranolol; not to exceed 3 doses/d
Pediatric DoseNot recommended
ContraindicationsDocumented hypersensitivity; documented ischemic cardiac, cerebrovascular, or peripheral vascular syndromes; vasospastic coronary artery disease; uncontrolled hypertension; basilar or hemiplegic migraine; within 24 h of ergot-type drugs (eg, methysergide, dihydroergotamine) or other 5-HT1 agonists; during or within 2 wk after discontinuing MAOIs
InteractionsToxicity 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
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsHypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur when administering this medication

Drug Category: Anticonvulsants

For use in acute and prophylactic treatment of migraine. Agents that interact with the GABAergic system seem to have a positive effect in reducing migraine attacks. Valproate and topiramate are most commonly used.

Drug NameTopiramate (Topamax)
DescriptionSulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiates inhibitory activity of neurotransmitter GABA. In addition, may block glutamate activity. Not necessary to monitor plasma concentrations to optimize therapy.
Adult Dose50 mg/d PO; titrate by 50 mg/d at 1-wk intervals to target dose of 200 mg bid; not to exceed 1600 mg/d
Pediatric Dose<2 years: Not established
2-16 years: 1-3 mg/kg PO initially; not to exceed 25 mg/d, then titrate dose upward by 1-3 mg/kg/d divided bid (not to exceed dosage increases of 25 mg) q1-2wk until total daily dose is 5-9 mg/kg/d divided bid
>16 years: Administer as in adults
ContraindicationsDocumented hypersensitivity
InteractionsPhenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants since may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsRisk of developing a kidney stone formation is increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop can lead to glaucoma (primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur); oligohidrosis and hyperthermia have been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures); may cause hyperchloremic, nonanion gap metabolic acidosis acute or chronic metabolic acidosis resulting in hyperventilation and nonspecific symptoms, such as fatigue and anorexia, or more severe adverse effects including cardiac arrhythmias or stupor
Chronic, untreated metabolic
acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate levels

Drug NameValproic acid (Depakote)
DescriptionNo evidence suggests that valproic acid is useful in the acute treatment of migraine headaches. Mechanism of action unknown.
Adult Dose250 mg PO bid initially; not to exceed 1 g/d
Pediatric Dose<16 years: Not established
>16 years: Administer as in adults
ContraindicationsDocumented hypersensitivity; hepatic disease/dysfunction
InteractionsCoadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsThrombocytopenia and abnormal coagulation parameters have occurred; the risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or a hemostasis/coagulation disorder occur; hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness

Drug Category: Ergot preparations

These agents are used in the acute treatment of migraine.

Drug NameDihydroergotamine (DHE 45, Migranal)
DescriptionAlpha-adrenergic blocking agent with direct stimulating effect on smooth muscle of peripheral and cranial blood vessels; depresses central vasomotor centers. Indicated to abort or prevent vascular headache when rapid control needed or when other routes of administration not feasible.
Adult Dose1 mg/mL injection: 1 mL IM/IV at attack's onset, then 1 mL after 1 h, if needed; not to exceed 2 mL IV or 3 mL IM per attack, 6 mL/wk; premedicate with metoclopramide (10 mg IV or IM) or another antiemetic
Intranasal administration: Spray once in each nostril, then repeat 15 min later; not to exceed 6 puffs/24 h and 8 puffs/wk
Pediatric DoseNot established
ContraindicationsCoronary or peripheral vascular disease; hypertension; impaired hepatic or renal function; sepsis; breastfeeding mothers
InteractionsIncreases effects of heparin and toxicity of nitroglycerin, propranolol, erythromycin, and clarithromycin
PregnancyX - Contraindicated; benefit does not outweigh risk
PrecautionsCaution in angina, hypertension, impaired renal or hepatic function, or peripheral vascular disease

Drug Category: Beta-adrenergic blockers

These agents are effective in prophylactic therapy, possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.

Drug NamePropranolol (Inderal)
DescriptionIndicated for prophylaxis of migraine headache. Mechanism of action unknown.
Adult Dose80 mg/d PO divided tid/qid initially; may increase to 160-240 mg/d PO
Pediatric DoseNot recommended
ContraindicationsDocumented hypersensitivity; asthma; sinus bradycardia; second- or third-degree AV block; overt heart failure; cardiogenic shock
InteractionsPotentiated by alcohol, CNS depressants, other antihypertensives, antithyroid drugs, haloperidol, chlorpromazine, and cimetidine; bradycardia with catecholamine-depleting drugs; antagonized by NSAIDs, barbiturates, rifampin, and phenytoin; may increase cardiac effects of calcium channel blockers, digitalis, and lidocaine; potentiates theophylline, antipyrine, and lidocaine; may block epinephrine; may interfere with glaucoma screening tests
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCHF, Wolff-Parkinson-White syndrome; renal or hepatic dysfunction; bronchospastic disease and COPD; diabetes; hyperthyroidism; surgery; SLE; avoid abrupt cessation; discontinue if results are poor after 4-6 wk of therapy

Drug Category: Nonsteroidal anti-inflammatory agents

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

Drug NameIbuprofen (Ibuprin, Advil, Motrin)
DescriptionFirst-line treatment for mild to moderately severe migraine events. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Adult Dose400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; not to exceed 3.2 g/d
Pediatric Dose20-70 mg/kg/d PO divided tid/qid; start at lower end of dosing range and titrate; not to exceed 2.4 g/d
ContraindicationsDocumented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding
InteractionsCoadministration 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
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCategory D in third trimester of pregnancy; caution in CHF, hypertension, and decreased renal and hepatic function; caution in coagulation abnormalities or during anticoagulant therapy

Drug NameNaproxen (Anaprox, Naprelan, Naprosyn)
DescriptionFor relief of mild to moderately severe pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult Dose500 mg PO, followed by 250 mg q6-8h; not to exceed 1.25 g/d
Pediatric Dose<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
ContraindicationsDocumented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
InteractionsProbenecid may increase toxicity; ibuprofen may decrease effects of loop diuretics; may prolong PT in patients receiving anticoagulants (watch for signs of bleeding); may increase serum lithium levels and risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity)
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAcute 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 NameKetorolac (Toradol)
DescriptionInhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Adult Dose30-60 mg IM initially, followed by 15-30 mg q6h prn; not to exceed 5 d of treatment
Pediatric DoseNot established; recommended dose is 0.4-1 mg/kg IM once
ContraindicationsDocumented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; do not administer into CNS
InteractionsCoadministration 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
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsCategory D in third trimester of pregnancy; 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 occur

Drug NameAspirin (Anacin, Ascriptin, Bayer Aspirin)
DescriptionTreats mild to moderately severe pain and headache. Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.
Adult Dose325-650 mg PO q4-6h; not to exceed 4 g/d
Pediatric Dose10-15 mg/kg/dose PO q4-6h; not to exceed 60-80 mg/kg/d
ContraindicationsDocumented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma
Because of association with Reye syndrome, do not use in children (age <16 y) with flu
InteractionsEffects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; 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
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsMay cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Drug Category: Antidepressants

These agents are used for prophylaxis (mechanism of action is independent of antidepressant effect, but unknown). Inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

Drug NameAmitriptyline (Elavil)
DescriptionAnalgesic for certain chronic and neuropathic pain. Mechanism of action in migraine headaches unknown.
Adult Dose10-300 mg PO qd in divided doses or hs; titrate dose to alleviate symptoms
Pediatric DoseNot recommended
ContraindicationsDocumented hypersensitivity; during or within 14 d of MAOIs; acute post-MI
InteractionsHyperpyretic crisis, convulsions, death with MAOIs; potentiates alcohol; CNS stimulation with reserpine; antagonized by barbiturates, carbamazepine, and phenytoin; paralytic ileus, hyperpyrexia with anticholinergics; blocks guanethidine; potentiated by hepatic enzyme inhibitors; monitor serum levels with cimetidine
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsCaution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly persons

Drug NameNortriptyline (Pamelor, Aventyl HCl)
DescriptionHas demonstrated effectiveness in the treatment of chronic pain. Mechanism of action in the treatment of migraine headaches unknown. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane this drug increases the synaptic concentration of these neurotransmitters in the central nervous system.
Pharmacodynamic effects such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play a role in its mechanisms of action.
Adult Dose10-125 mg PO qd in divided doses or hs; titrate dose to alleviate symptoms
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; narrow-angle glaucoma; do not administer to patients who have taken MAOIs in past 14 d
InteractionsCimetidine may increase nortriptyline levels when used concurrently; nortriptyline may increase prothrombin time in patients stabilized with warfarin
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; because of pronounced effects in cardiovascular system, best to avoid in elderly persons

Drug Category: Analgesic, non-narcotics

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

Drug NameIsometheptene, dichloralphenazone, acetaminophen (Midrin, Midchlor, Isocom)
DescriptionAcetaminophen/aspirin combinations are indicated for initial migraine events. Isometheptene acts by constricting dilated cranial and cerebral arterioles, reducing stimuli that lead to vascular headaches. Acetaminophen raises threshold to painful stimuli, thus exerting an analgesic effect against all types of headaches.
Adult Dose2 cap PO initially, followed by 1 cap PO q1h until desired response obtained; not to exceed 5 cap per 12 h
Pediatric DoseNot recommended
ContraindicationsDocumented hypersensitivity; glaucoma, hypertension, organic heart disease, severe renal disease, or hepatic disease; do not administer within 2 wk of taking MAOI
InteractionsConcurrent use of MAOIs with isometheptene may result in severe headache, hypertension, and hyperpyrexia, which, in turn, may result in hypertensive crisis
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in hypertension, peripheral vascular disease, and recent cardiovascular injuries

Drug NameAcetaminophen (Tylenol, Feverall, Aspirin-Free Anacin)
DescriptionDOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.
Adult Dose325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; known G-6-P deficiency
InteractionsRifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsHepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen is contained in many OTC products and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose

Drug Category: Barbiturates

These agents are used for acute treatment of mild-to-moderate migraine headaches.

Drug NameButalbital compound (Fioricet or Fiorinal)
DescriptionDrug combination for tension headaches. Barbiturate component has generalized depressant effect in CNS.
Adult Dose1-2 tab or cap PO q4h prn; not to exceed 6 doses/d
Pediatric DoseNot recommended
ContraindicationsDocumented hypersensitivity; porphyria; varicella or influenza in teenagers; bleeding or coagulation disorders; peptic ulcer; third trimester of pregnancy
InteractionsEffects decreased by coadministration of phenothiazines, quinidine, tricyclic antidepressants, theophylline, haloperidol, chloramphenicol, ethosuximide, corticosteroids, warfarin, doxycycline, and beta-blockers; effects are increased with coadministration of CNS depressants, methylphenidate, valproic acid, propoxyphene, and benzodiazepines; aspirin may increase effect of anticoagulants
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsCaution in elderly persons and those who are debilitated; caution in patients with history of substance abuse, impaired hepatic or renal function, acute abdomen, depression, suicidal tendencies, asthma, bleeding disorders, or gastritis; monitor blood pressure, BUN, and uric acid levels



Further Inpatient Care

  • Refractory migraine on maximum medical treatment may require inpatient care.

Further Outpatient Care

  • Avoid migraine precipitants.
  • Take medications as prescribed. Most patients are able to benefit from some form of antimigrainous therapy.
  • Closely follow up with a primary care physician or neurologist.

In/Out Patient Meds

Deterrence/Prevention

  • Avoid migraine precipitants (see Causes)

Complications

  • Status migrainosus

Prognosis

  • Usually good: Most patients gain some improvement with treatment.

Patient Education



Medical/Legal Pitfalls

  • Beware of any potentially dangerous intracranial process (eg, subarachnoid hemorrhage, aneurysm, meningitis) that may present as an atypical migraine headache. Consider sight-threatening entities such as giant cell arteritis or narrow-angle glaucoma.



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Migraine Headache: Neuro-Ophthalmic Perspective excerpt

Article Last Updated: Oct 3, 2006