Migraine in Adults

Background

• Migraine is a common primary headache disorder, is 1 of the leading causes of disability worldwide, and has a profound impact on people living with the disorder, their families, healthcare systems, and society.
• The pathophysiology of migraine is not fully understood but likely involves multiple components of the central and peripheral nervous system. It is recurrent in nature and classically presents as moderate-to-severe head pain lasting 4-72 hours. It is typically unilateral with a pulsating quality, accompanied by nausea, vomiting, photophobia, and/or phonophobia, and may be preceded by aura that consists of sensory, motor, or language symptoms.
• In addition to migraine with or without aura, migraine is commonly classified as follows:
  • By frequency:
    • Episodic migraine is defined as having headaches on < 15 days/month.
    • Chronic migraine is defined as having headache on ≥ 15 days/month for > 3 months, including migraine features ≥ 8 days/month.
  • As intractable, or not: Intractable headaches are considered to be resistant to multiple pharmacotherapies and/or are poorly controlled. Status migrainosus may occur with migraine headache lasting > 72 hours.
• Several other subtypes of migraine have been described, including familial hemiplegic migraine and migraine with brainstem aura.
• Migraine is associated with a number of other conditions and disorders including sleep-related disorders, obesity, and neurologic, psychiatric, cardiovascular, pregnancy-related, and gynecologic conditions.
• Complications associated with migraine include reduced quality of life, increased work absences or reduced productivity when at work, disrupted family relationships, and increased risk of stroke, pain, and other disorders such as asthma, anxiety, and depression.

Evaluation

• Ask about characteristics of headache attacks, including:
  • unilateral location, gradual onset, pulsating quality, moderate-to-severe intensity, and aggravation by or causing avoidance of physical activities such as walking or climbing stairs
  • if attacks are typically accompanied by nausea, vomiting, photophobia, or phonophobia
  • the duration of attacks (typical migraine duration 4-72 hours), how often attacks occur, and how many attacks the patient has had in their life
  • the presence of any combination of visual, hemisensory, or language abnormalities occurring ≤ 60 minutes prior to headache onset, spreading gradually over ≥ 5 minutes (indicative of aura)
  • any potential "triggers" such as food, sensory stimuli, events, or other factors preceding attacks
• Ask about the disabling effects of migraine on the patient's life, including migraine-associated disability, quality of life, and functional disability affecting family, work, and other life functions. Validated and succinct measures of migraine-related disability include the Migraine Disability Assessment (MIDAS) and Migraine-specific Quality of Life Questionnaire (MSQ).
• Ask about symptoms that may suggest a potentially serious secondary cause of headache, including:
  • numbness or tingling that is not consistent with aura-like sensory symptoms
  • unusual aura - symptoms lasting > 60 minutes or beginning or persisting after headache pain dissipates
  • unusual headache characteristics, including;
    • change in headache patterns such as increased frequency (particularly daily headaches) and intensity
    • severe headache pain ("worst headache of life") or headache causing awakening from sleep
    • headache lasting > 72 hours
    • very sudden-onset headache or neurologic symptoms
    • persistent pain on only 1 side of head
    • headache triggered by effort, exercise, orgasm, coughing, sneezing, a particular body position/posture, or during Valsalva maneuver
    • headache associated with fever, blurred vision, seeing halos around lights, systemic illness, or change in personality or mental status
    • new onset headache after age 50 years
    • headache refractory to previously effective treatment
  • jaw pain (claudication)
  • previous head trauma
• Conduct a thorough physical exam. Positive findings may suggest a potentially serious secondary cause of headache, and normal findings may reassure the patient. Concerning findings include papilledema, tenderness over the temporal artery, and signs of meningeal inflammation. See Headache - Approach to the Adult Patient for additional information.
• Diagnose migraine in patients with a typical headache pattern in a clinical exam.
• Routine blood tests, neuroimaging, electroencephalography, or other testing are not necessary for most patients, especially among those with a normal neurologic examination, but it may be considered to evaluate for other conditions.

Management

• For treatment of acute migraine attack:
  • For patients presenting to the emergency department, consider IV metoclopramide (combined with IV prochlorperazine) 10-20 mg or subcutaneous sumatriptan 6 mg (however, avoid in patients who have had ergotamine, dihydroergotamine (DHE), or a triptan within the past 24 hours).
  • IV magnesium might be considered for pain reduction in selected patients with acute migraine, but adverse effects may include flushing, hypotension, vasodilation, muscle paralysis, and cardiac conduction abnormalities. Do not use IV magnesium in patients with kidney disease or myasthenia gravis.
  • For mild-to-moderate migraine attacks:
    • If nausea and/or vomiting are absent, consider simple or combination oral analgesics such as aspirin 900-1,000 mg, ibuprofen 400 mg, or acetaminophen 1,000 mg or aspirin plus acetaminophen plus caffeine.
    • If nausea and/or vomiting are present, consider oral or rectal antiemetic in combination with simple or combination oral analgesics.
  • For moderate-to-severe migraine attacks:
    • If nausea and/or vomiting are absent, consider:
      • sumatriptan 50-100 mg orally or other triptans if sumatriptan not effective
      • combination therapy with sumatriptan 50-85 mg and naproxen 500 mg
    • If vomiting or severe nausea are present:
      • Consider oral or rectal antiemetic and nonoral migraine-specific medications such as sumatriptan subcutaneously or intranasally, zolmitriptan intranasally or disintegrating tablet, or parenteral DHE.
      • Triptans have potential adverse effects to the fetus in animal studies, but evidence in humans is limited. Consider in pregnant women with severe migraine only if potential benefits outweigh harms.
      • Do not use triptans in patients with ischemic heart disease, previous myocardial infarction, coronary vasospasm, cerebral or peripheral vascular disease, or severe or uncontrolled hypertension.
        • Do not use within 24 hours of using another triptan or an ergot derivative (due to possibility of additive vasoconstriction).
        • If triptans or DHE are contraindicated, consider oral calcitonin gene-related peptide (CGRP) receptor antagonists such as rimegepant 75 mg orally disintegrating tablet or ubrogepant 50 mg or 100 mg orally.
  • Frequent analgesic use can cause medication overuse headache.
  • See Migraine - Treatment of Acute Attack in Adults for a complete discussion of options including detailed recommendations and evidence summaries.
• For migraine prophylaxis:
  • First-line medication options include:
    • propranolol starting dose 20-40 mg orally twice daily (or 10 mg twice daily in young women) and then increased by 20 mg twice daily every 1-2 weeks as tolerated to 40-240 mg/day in divided doses (or once daily if long-acting formulation)
    • timolol 5-30 mg/day
    • metoprolol starting dose 25-50 mg orally twice daily and then increased as tolerated to 100-200 mg/day in divided doses (or once if sustained-release formulation)
    • frovatriptan 2.5 mg orally twice daily from 2 days before to 3 days after menstruation onset for short-term prophylaxis of menstrual migraine
    • topiramate
      • starting dose 15-25 mg orally at bedtime and then increased by 15-25 mg/day/week as tolerated to 100 mg/day at bedtime (may also consider 50 mg at bedtime or up to 200 mg/day in divided doses)
      • considerations for optimal dosing include lack of evidence for 25 mg/day for prevention of episodic migraine, decreased efficacy for 50 mg/day compared with 100-200 mg/day (which has comparable efficacy), and increased adverse events for > 200 mg/day
    • amitriptyline starting dose 10 mg orally at or 1 hour before bedtime and then increased by 10 mg every 1-2 weeks as tolerated to 10-150 mg/day.
    • consideration of botulinum toxin A for prophylaxis only in patients who have not responded to at least 3 prior pharmacologic prophylaxis therapies and the condition is appropriately managed for medication overuse; considerations for optimal dosing include:
      • 5 units/injection intramuscularly for patients with chronic migraine
      • 31 injections of 0.1 mL in 7 head and neck muscles
  • CGRP monoclonal antibodies also have evidence for a large effect on migraine frequency and duration but are an emerging therapy and have limited evidence for long-term efficacy and safety outcomes.
  • Also consider lifestyle management (such as diet, exercise, and sleep hygiene) and nonpharmacologic strategies (such as counseling).
  • See Migraine Prophylaxis in Adults for a complete discussion of options including detailed recommendations and evidence summaries.