Headache, Migraine

Benjamin N. Schneider, MD Reviewed 06/2017

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Subject: Headache, Migraine

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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. Migrainelike attacks are superimposed on a daily or neardaily headache pattern (e.g., tension headaches) >15 headache days/month for at least 3 months.
    • ▪ Menstrual-related (molimina) 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. 


  • Screening mnemonic “POUND”: Pulsating, duration of to 72 hOurs, Unilateral, Nausea, Disabling

    • ▪ + Likelihood ratio (LR) = 24 for migraine diagnosis if 4 of 5 criteria present
    • ▪ + LR = 0.41 for migraine diagnosis if ≤2 criteria present 2
  • Headache usually begins with mild pain escalating into unilateral (30-40% bilateral) throbbing (40% nonthrobbing) pain lasting 4 to 72 hours.

  • Intensified by movement and associated with systemic manifestations: nausea (87%), vomiting (56%), diarrhea (16%), photophobia (82%), phonophobia (78%), muscle tenderness (65%), light-headedness (72%), and vertigo (33%)

  • May be preceded by aura

    • ▪ Visual disruptions are most common—scotoma, hemianopsia, fortification spectra, geometric visual patterns, and occasionally hallucinations.
    • ▪ Somatosensory disruption in face or arms
    • ▪ Speech difficulties
  • Obtain headache profile: number of headaches per month, number of days per month headaches limit daily activities, and frequency and amount of all headache medications used.

  • Migraine disability assessment (MiDAS) is a useful tool to assess level of disability and correlates well with headache diaries.

  • Identify possible triggers (e.g., stress, sleep disturbance, food, caffeine, alcohol).


Neurologic exam should be performed including funduscopy; 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.

Pediatric Considerations

NSAIDs and triptans appear to be effective for the acute treatment of children and adolescents with migraine. Triptans may have better efficacy than NSAIDs but also have higher rates of side effects. Not all triptans are approved for use in children 4

Pregnancy Considerations

  • Frequency may decrease in 2nd and 3rd trimesters.

  • Nonpharmacologic methods are preferred.

  • No treatment drug has FDA approval in 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 ruled 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:
      • * Acetaminophen is effective for mild to moderate attacks and when combined with metoclopramide has relief rates similar to triptans 5[A].
      • * NSAIDs are inexpensive and effective in up to 60% of cases 5[B].
      • * Aspirin-acetaminophen-caffeine (Excedrin Migraine) is an inexpensive, OTC treatment with efficacy higher than its components 5[B].
    • ▪ Moderate to severe attacks:
      • * Triptans when OTC agents fail for moderate attacks OR first line for severe attacks 6[B]
      • * All triptans have similar efficacy/tolerability, but patients often respond better to one triptan over another 5[C].
    • ▪ Suggested initial doses 6[B]:
    • ▪ Combination triptan and NSAID: Sumatriptan 85 mg/naproxen 500 mg PO at onset of headache show improved efficacy over either alone.
    • ▪ Antiemetics: Dopamine antagonists are excellent adjunctive medications 5,6[B].
  • Contraindications to treatments

    • ▪ Avoid triptans and ergots in coronary artery or peripheral vascular disease, uncontrolled hypertension, and complicated migraine (e.g., brainstem or hemiplegic migraine).
    • ▪ Do not combine triptans or use with ergots or MAOIs.
    • ▪ Avoid opioids or butalbital in patients with frequent migraines.
  • Precautions

    • ▪ Frequent use of acute-treatment drugs can result in MOH.
    • ▪ Triptan adverse reactions are common and include chest pressure, flushing, weakness, dizziness, feeling of warmth, and paresthesias.
  • Second-line abortive treatment

    • ▪ Ergotamines (e.g., dihydroergotamine SC, Migranal intranasal): drug of choice in status migrainosus 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 7.
  • First-line preventative treatment

    • ▪ Should not be limited to pharmacologic agents; trigger reduction, biofeedback, relaxation techniques, and CBT 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. Trial and error is needed to determine optimal therapy.
  • The American Migraine Prevalence and Prevention Study suggests prophylactic treatment when:

    • ▪ Quality of life is severely impaired.
    • ▪ ≥6 headache days/month, ≥4 headache days/month of moderate severity, or ≥2 headache days/month of severe impairment
    • ▪ Migraines do not respond to abortive treatment.
    • ▪ Frequent, very long, or uncomfortable auras occur.
  • Prevention of episodic migraine, divalproex, valproate, topiramate, metoprolol, and timolol are effective in reducing frequency/severity 6[A].

    • ▪ NSAIDs are probably effective for prevention in people with predictable triggers (menses, etc.) but pose a risk for MOH 8[B].
    • ▪ For treatment/prevention of chronic migraine, botulinum toxin A (Botox) significantly reduces frequency of headache days.


  • Obscure diagnosis, concomitant medical conditions, significant psychopathology

  • Unresponsive to usual treatment

  • Analgesic-dependent headache patterns


  • Butterbur (Petasites hybridus; Petadolex): 50 to 75 mg BID 8[A]—Use caution with CYP3A4 meds.

  • Riboflavin (vitamin B2): 400 mg/day 8[B]

  • Magnesium: 400 mg/day 8[B]

  • MIG-99 (Feverfew): 6.25 mg TID 8[B]

  • Histamine SC: 1 to 10 ng twice weekly 8[B]

  • Acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment and has fewer adverse effects 9[B].


  • Consider if diagnosis not clear; status migrainosus; may need to exclude intracranial bleeds; TIA; stroke; monitor vital signs and patient comfort.

  • Fluids are a necessary part of inpatient management. Keeping patients hydrated and on antiemetics around the clock may be helpful.

  • 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 to decrease frequency and severity of 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.


  • Status migrainosus (>72 hours)

  • Cerebral ischemic events (rare)

  • MOH: headache occurring 10 or more days/month for >3 months as a consequence of regular overuse of an acute or symptomatic headache medication. Likelihood with butalbital > opiates > triptans > NSAIDs.


Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia.  2013;33(9):629–808. [View Abstract on OvidInsights]
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. [View Abstract on OvidInsights]
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. [View Abstract on OvidInsights]
Richer  L, Billinghurst  L, Linsdell  MA, et al. Drugs for the acute treatment of migraine in children and adolescents. Cochrane Database of Syst Rev.  2016;(4):CD005220. [View Abstract on OvidInsights]
Becker  WJ. Acute migraine treatment in adults. Headache.  2015;55:778–793. [View Abstract on OvidInsights]
Gilmore  B, Michael  M. Treatment of acute migraine headache. Am Fam Physician.  2011;83(3):271–280. [View Abstract on OvidInsights]
Taylor  FR, Kaniecki  RG. Symptomatic treatment of migraine: when to use NSAIDs, triptans, or opiates. Curr Treat Options Neurol.  2011;13(1):15–27. [View Abstract on OvidInsights]
Holland  S, Silberstein  SD, Freitag  F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments 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):1346–1353. [View Abstract on OvidInsights]
Linde  K, Allais  G, Brinkhaus  B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev.  2009;(6):CD001218. [View Abstract on OvidInsights]


Algorithm: Headache, Chronic 



Algorithm: Headache, Chronic 


  • 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 mild attacks; migraine-specific treatments 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.

  • In those with frequent or highly debilitating migraines, prophylactic treatment should be encouraged.