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Headache, Migraine
Benjamin N. Schneider, MD
image BASICS
Recurrent headache disorder manifesting in attacks lasting 4 to 72 hours. Typical characteristics are unilateral location, pulsating quality, moderate or severe intensity, aggravation by physical activity, and association with nausea and/or photophobia and phonophobia (1).
  • Most frequent subtypes of migraine (1):
    • Without aura (common migraine): defining >80% of attacks, often associated with nausea, vomiting, photophobia, and/or phonophobia
    • With aura (classic migraine): visual or other types of fully reversible neurologic phenomenon lasting 5 to 60 minutes
    • Chronic (transformed) migraine: chronic headache pattern evolving from episodic migraine. Migraine-like attacks are superimposed on a daily or near-daily headache pattern (e.g., tension headaches), >15 headache days/month for at least 3 months.
    • Menstrual-related (moliminal) migraine: associated with onset of menstrual period
  • Rare but important subtypes (1):
    • Status migrainosus: debilitating migraine lasting >72 hours
    • With brainstem aura (basilar migraine): brainstem symptoms—dysarthria, vertigo, tinnitus, or ataxia, which are fully reversible and lasting 5 to 60 minutes.
    • Hemiplegic migraine: aura consisting of fully reversible hemiplegia and/or hemiparesis
    • Recurrent painful ophthalmoplegic neuropathy (ophthalmoplegic migraine): neuralgia accompanied by paresis of an ocular cranial nerve with ipsilateral headache
    • Retinal: repeated attacks of monocular visual disturbance, including scintillations, scotomata, or blindness, associated with migraine headache
Female > male (3:1)
  • Affects >28 million Americans
  • Adults: women 18%; men 6%
  • No longer believed to be primarily vascular in etiology; rather, cortical spreading depolarization/depression
  • Trigeminovascular hypothesis: hyperexcitable trigeminal sensory neurons in brainstem are stimulated and release neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP),leading to vasodilation and neurogenic inflammation.
  • >80% of patients have a positive family history.
  • Familial hemiplegic migraine has been shown to be linked to chromosomes 1, 2, and 19 (1).
  • Family history of migraine
  • Female gender
  • Stress
  • Menstrual cycle, hormones
  • Sleep pattern disruption
  • Diet: skipped meals (40-56%), alcohol (29-35%), chocolate (19-22%), cheese (9-18%), caffeine overuse (14%), monosodium glutamate (MSG) (12%), and artificial sweeteners (e.g., aspartame, sucralose)
  • Medications: estrogens, vasodilators
  • Avoid precipitants of attacks.
  • Biofeedback, education, and psychological intervention
  • Lifestyle modifications are the cornerstone of prevention: sleep hygiene, stress management, healthy diet, and regular exercise.
  • Prophylactic medication if attacks are frequent, severely debilitating, or not controlled by acute interventions
  • Depression, psychiatric disorders
  • Sleep disturbance (e.g., sleep apnea)
  • Cerebral vascular disease
  • Peripheral vascular disease
  • Seizure disorders
  • Irritable bowel syndrome
  • Obesity
  • Patent foramen ovale (PFO)
  • Medication overuse headache (MOH)
Migraine is a clinical diagnosis; thorough history and neuro examination are usually all that are necessary.
Neurologic exam should be performed including fundoscopy; abnormalities consistent with other causes to severe headaches MIGHT include the following:
  • Gait abnormalities and other new cerebellar findings
  • Loss of gross and/or fine motor function
  • Altered mental status including possible hallucinations (visual, auditory, olfactory)
  • Short-term memory loss
  • Other primary headache syndromes
  • If focal neurologic signs/symptoms are present, consider transient ischemic attack (TIA) or stroke.
  • Secondary headaches: tumor, infection, vascular pathology, prescription or illicit drug use (MOH)
  • Psychiatric disease
  • Rarely, atypical forms of epilepsy
Neuroimaging is appropriate ONLY with suspicious symptomatology and/or an abnormality on physical examination (3). Other red flags include the following:
  • New onset in patient >50 years of age
  • Change in established headache pattern
  • Atypical pattern or unremitting/progressive neurologic symptoms
  • Prolonged or bizarre aura
  • Type of imaging: Data are insufficient to make evidence-based recommendations regarding relative sensitivity of MRI compared with CT in the evaluation of migraine or other nonacute headache
  • EEG is NOT indicated unless evaluating loss of consciousness or altered mental status.
Pregnancy Considerations
  • Frequency may decrease in 2nd and 3rd trimesters.
  • Nonpharmacologic methods are mainstay of treatment.
  • No treatment drug has an FDA approval during pregnancy.
    • Acetaminophen (Category C) triptans, antiemetics, and short-acting opioids can be considered for acute headaches during pregnancy.
    • Ergotamines are contraindicated (Category X).
    • Avoid herbal remedies.
    • Sumatriptan, naratriptan and opiates are pregnancy Category C—risk cannot be rule out but early data suggest no increase in birth defects.
    • Sumatriptan by injection is ideal for breastfeeding women with disabling migraines.
    • Propranolol (Category C) is effective for prophylaxis during pregnancy and lactation.
  • Most patients manage attacks with self-care.
  • Cold compresses to area of pain
  • Withdrawal from stressful surroundings
  • Sleep is desirable.
  • See also “General Prevention.”
  • First-line abortive treatments
    • Mild to moderate attacks:
      • NSAIDs, such as ibuprofen, naproxen, and diclofenac are inexpensive and effective in up to 60% of cases.
      • Aspirin 500 mg-acetaminophen 500 mg-caffeine 130 mg (AAC) combination (e.g., Excedrin Migraine) is an inexpensive, nonprescription, and FDA-approved treatment.
    • Moderate to severe attacks:
      • Triptans are preferred when OTC agents fail for mild/moderate attacks OR as initial treatment for moderate to severe attacks:
      • All triptans have similar efficacy and tolerability, but some patients may respond better to one triptan over another.
      • P.441

      • Early intervention with triptans during the aura, prior to onset of pain, prevent headache 89% of the time.
    • Common adverse drug reactions include chest pressure, flushing, weakness, dizziness, feeling of warmth, and paresthesia.
      • Suggested initial doses (refer to individual labeling for more detailed dosing instructions)
      • Sumatriptan 100 mg PO; 6 mg SQ; 20 mg intranasal
      • SQ route quickest onset but most side effects
      • Eletriptan 40 mg PO
      • Rizatriptan 10 mg PO
      • Zolmitriptan 2.5 mg PO; 5 mg intranasal
      • Naratriptan 2.5 mg PO
      • Frovatriptan 2.5 mg PO
        • 44-77% of patients taking triptans report complete pain relief within 2 hours.
        • Frovatriptan and naratriptan have slow onset but long half-lives.
    • Combination triptan and NSAID: sumatriptan 85 mg/naproxen 500 mg PO at onset of HA show improved efficacy over either alone.
    • Antiemetics: Consider antinausea medications that antagonize dopamine receptors:
      • Metoclopramide, prochlorperazine
      • Emergency therapy; 10 to 25 mg single dose (4)[A]
  • Contraindications to treatments
    • Avoid 5-HT-1 agonists (triptans) and ergots in coronary artery disease, peripheral vascular disease, uncontrolled hypertension, and complicated migraine (e.g., brainstem or hemiplegic migraine).
    • Triptans should not be used with ergots, MAOI, or other triptans.
    • Avoid opioids or butalbital in patients with frequent migraines.
  • Precautions
    • Frequent use of acute-treatment drugs may lead to increase in migraine patterns and medication overuse headache.
  • Second-line abortive treatment
    • Acetaminophen 1,000 mg or aspirin 975 mg plus the addition of a dopamine antagonist (e.g., metoclopramide 10 mg) may be as effective as PO sumatriptan 100 mg for acute migraine.
    • Ergotamines (e.g., dihydroergotamine SC, Migranal intranasal): drug of choice in status migrainosus and nonpregnant patients but limited use due to side effects and replaced by triptans
    • Opiate use is controversial and can contribute to medication overuse or chronic daily headache with use as few as 8 days per month (5).
      • IV dexamethasone: Use as adjunctive
  • First-line preventative treatment
    • Prevention should not be limited to pharmacologic agents. Trigger reduction, biofeedback, relaxation techniques, and cognitive behavioral therapy have evidence of efficacy.
    • Lifestyle modifications should be recommended for all migraine sufferers.
    • ˜38% of migraineurs need preventative therapy, but only 3-13% use it (6). Trial and error is needed to determine optimal therapy.
  • The American Migraine Prevalence and Prevention Study recommendations suggest prophylactic treatment when:
    • Quality of life is severely impaired.
    • ≥6 headache days/month of any severity, ≥4 headache days/month of moderate severity, or ≥2 headache days/month of severe impairment.
    • Migraine unresponsive to abortive treatment.
    • Frequent, very long, or uncomfortable auras occur.
  • For prevention of episodic migraine, divalproex, valproate, topiramate, metoprolol, and timolol are effective for migraine prevention and should be offered to patients to reduce attack frequency and severity (6)[A].
    • NSAIDs are probably effective for migraine prevention, especially for people with predictable triggers (menses, etc.) but pose a risk for MOH.
  • For treatment/prevention of chronic migraine, the FDA has approved botulinum toxin A (Botox), as it significantly reduced the frequency of headache days in chronic migraineurs.
  • Obscure diagnosis, concomitant medical conditions, significant psychopathology
  • Unresponsive to usual treatment
  • Analgesic-dependent headache patterns
  • Butterbur (Petasites hybridus; Petadolex): 50 to 75 mg BID
    • Use caution with CYP3A4 meds.
  • Riboflavin (vitamin B2): 400 mg/day
  • Magnesium: 400 mg/day
  • MIG-99 (feverfew): 6.25 mg TID
  • Histamine SC: 1 to 10 ng twice weekly
  • Acupuncture is at least as effective as, or possibly more effective than prophylactic drug treatment and has fewer adverse effects.
Admission Criteria/Initial Stabilization
Consider if diagnosis not clear; status migrainosus; may need to exclude intracranial bleeds, TIA, stroke; monitor vital signs and patient comfort.
IV Fluids
Fluids are a necessary part of inpatient management.
Discharge Criteria
Judgment based on patient's overall clinical status and patient's ability to tolerate PO medications
  • Early intervention is key at the onset of an attack.
  • Preventative treatment should aim to decrease frequency and severity of acute attacks, make acute treatments more efficacious, and minimize adverse drug reactions.
Patient Monitoring
  • Monitor frequency of attacks, pain behaviors, and medication usage via headache diary.
  • Encourage lifestyle modifications. Counsel patients and manage expectations.
Educate patients about migraine triggers.
  • With increasing age, there may be a reduction in severity, frequency, and disability of attacks.
  • Most attacks subside within 72 hours.
1. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013;33(9):629-808.
2. Detsky ME, McDonald DR, Baerlocher MO, et al. Does this patient with headache have a migraine or need neuroimaging? JAMA. 2006;296(10):1274-1283.
3. Loder E, Weizenbaum E, Frishberg B, et al. Choosing wisely in headache medicine: the American Headache Society's list of five things physicians and patients should question. Headache. 2013;53(10):1651-1659.
4. Gilmore B, Michael M. Treatment of acute migraine headache. Am Fam Physician. 2011;83(3):271-280.
5. Taylor FR, Kaniecki RG. Symptomatic treatment of migraine: when to use NSAIDs, triptans, or opiates. Curr Treat Options Neurol. 2011;13(1):15-27.
6. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17): 1337-1345.
See Also
Algorithm: Headache, Chronic
  • G43.909 Migraine, unsp, not intractable, without status migrainosus
  • G43.109 Migraine with aura, not intractable, w/o status migrainosus
  • G43.409 Hemiplegic migraine, not intractable, w/o status migrainosus
Clinical Pearls
  • Migraine is a chronic headache disorder of unclear etiology often characterized by unilateral, throbbing headaches that may be associated with additional neurologic symptoms.
  • Accurate diagnosis of migraine is crucial.
  • Consider nonspecific analgesics for milder attacks; migraine-specific treatments (triptans) for more severe attacks.
  • Avoid opiates and barbiturates as well as frequent (>8/month) use of triptans or NSAIDs to avoid creating an MOH.
  • All patients should be counseled on lifestyle modifications and trigger identification.
  • Those with frequent or highly debilitating migraines prophylactic treatment should be encouraged.