Headache

Randolph W. Evans, M.D
Baylor College of Medicine, Houston, TX

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

Migraine

• Recurrent unilateral or bilateral, pulsating, mild to severe headache, exacerbated by physical activity, often beginning in frontotemporal or ocular regions
• Pain in face, jaw, and neck are common
• Pain usually accompanied by nausea, photophobia, or phonophobia
• Visual aura in 20% of migraineurs
• Untreated or unsuccessfully treated episodes last from 4 to 72 hours; more than 72 hours is migraine status
• 85% of migraineurs report triggers or precipitating factors
• Episodic if ≤ 15 days/month

• Pressing or tightening in quality, mild to moderate in intensity, and bilateral in location
• No worse with physical activity
• Either phonophobia or photophobia, but not both
• Not accompanied by nausea or vomiting
• Duration without treatment 30 minutes to 7 days

• Frequency of 15 or more days a month for greater than 3 months

• Transformed migraine: often from medication abuse, stress, anxiety, or depression
• Chronic tension headache
• Hemicrania continua: rare, associated with ptosis, lacrimation, nasal congestion; responds to indomethacin
• New daily persistent headache

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Differential Diagnosis

• Extensive: over 300 different types and causes
• For "first or worst" headaches, consider possibility of subarachnoid hemorrhage
• For new-onset headache in persons > 50 yr, consider temporal arteritis as the cause

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Best Tests

• History and physical examination usually sufficient for diagnosis
• CT and MRI rarely abnormal when neurologic exam is normal
• Consider testing for the atypical patient or the one with red flags (e.g., abnormal neurologic exam, worst headache, thunderclap headache, onset in persons > 50 yr; change in attack frequency, severity, clinical features; headache not responding to treatment; new-onset headache in patients with history of cancer or HIV positive)
• Blood tests generally not useful, except as baseline before beginning medications
• Lumbar puncture may be helpful for diagnosis of meningitis, subarachnoid hemorrhage, carcinomatosis, pseudotumor cerebri; usually performed after doing CT or MRI

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Best Therapy

Migraine

• Treatment is more effective with any medication when given when headache is mild rather than moderate or severe

• Acetaminophen: efficacy rating (on a scale of 0 to 4): 2+
  • Dose: 750–1,000 mg
• Aspirin: efficacy rating (on a scale of 0 to 4): 2+
  • Dose: 650 mg
• Ibuprofen: efficacy rating (on a scale of 0 to 4): 2+
  • Dose: 400–800 mg
• Acetaminophen + aspirin + caffeine: efficacy rating (on a scale of 0 to 4): 3+
  • Dose: 500 mg acetaminophen; 500 mg aspirin; 130 mg caffeine

• Isometheptene mucate 65 mg + dichloralphenazone 100 mg + acetaminophen 325 mg: efficacy rating (on a scale of 0 to 4): 3+
  • Dose: 2 capsules at onset followed by 1 capsule q. 1 hr (max 5/24 hr)
• Butalbital 50 mg + aspirin 325 mg: efficacy rating (on a scale of 0 to 4): 3+
  • Can lead to medication overuse headache and habituation
  • Dose: 2 capsules q. 4–6 hr
• Acetaminophen 325 mg + caffeine 40 mg + codeine 30 mg: efficacy rating (on a scale of 0 to 4): 3+
  • Can lead to medication overuse headache and habituation
  • Dose: 2 capsules q. 4-6 hr
• Butorphanol nasal spray: efficacy rating (on a scale of 0 to 4): 3+. For patients who cannot keep oral drugs down or do not respond to other medications
  • Can lead to medication overuse headache and habituation
  • Dose: 1 spray q. 4 hr p.r.n.
• Triptans: Contraindicated in patients with ischemic heart disease or those at risk for unrecognized coronary artery disease, peripheral vascular disease, cerebrovascular disease, and uncontrolled hypertension. Patients may respond differently to different triptans.
  • Almotriptan (Axert): efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 12.5 mg
    • Cost/mo: $239/12 tabs
  • Eletriptan (Relpax): efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 20 mg or 40 mg
    • Cost/mo: $136/6 tabs
  • Frovatriptan (Frova): efficacy rating (on a scale of 0 to 4): 3+
    • Minimal side effects and less recurrence
    • Dose: 2.5 mg
    • Cost/mo: $210/9 tabs
  • Naratriptan (Amerge): efficacy rating (on a scale of 0 to 4): 3+
    • Minimal side effects and less recurrence
    • Dose: 2.5 mg
    • Cost/mo: $264/9 tabs
  • Rizatriptan (Maxalt) tab and MLT (orally dissolving wafer): efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 10 mg
    • Cost/mo: $281/12 tabs or MLT
  • Sumatriptan (Imitrex): efficacy rating (on a scale of 0 to 4): 4+; 4+ for subcutaneous or intranasal for patients with nausea/vomiting; subcutaneous administration provides the fastest and highest efficacy of all the triptans
    • Dose: 25, 50, 100 mg tab; 20 mg nasal spray; 6 mg S.C.
    • Cost/mo: $227/9 100 mg tabs; $248/6 20 mg nasal inhalers; $471/5 vials for S.C. injection
  • Sumatriptan/naproxen sodium (Treximet): efficacy rating (on a scale of 0 to 4): 4+
    • Dose: sumatriptan 85 mg, naproxen sodium 500 mg
    • Cost: $200/9 tabs
  • Zolmitriptan ( Zomig): tab and ZMT (orally disintegrating tablet) and nasal spray; efficacy rating (on a scale of 0 to 4): 4+
    • Minimal side effects and less recurrence
    • Dose: 2.5 mg or 5 mg tab or ZMT and 5 mg nasal spray
    • Cost/mo: $140/6 2.5 mg tabs or ZMT; $202/6 single-use bottles of 5 mg nasal spray
• Dihydroergotamine nasal spray: efficacy rating (on a scale of 0 to 4): 3–4+
  • Minimal side effects and low recurrence rate; cannot be given within 24 hr of a triptan
  • Ergot derivative; contraindicated in the following:
    • Ischemic heart disease
    • Peripheral arterial disease
    • Severe hepatic or renal disease
    • Pregnancy
    • Patients taking protease inhibitors or macrolide antibiotics
  • Dose: 0.5 mg in each nostril; may repeat once after 15 min
  • Cost/mo: $869/8 ampules

• I.V. fluids and electrolytes may be needed for intractable vomiting

• Sumatriptan: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 4–6 mg S.C.
• Dihydroergotamine: efficacy rating (on a scale of 0 to 4): 4+
  • May cause nausea (combine with antiemetic); do not use within 24 hr of a triptan
  • Dose: 0.5–1 mg by slow I.V.
• Prochlorperazine: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 5–10 mg I.V.
• Ketorolac: efficacy rating (on a scale of 0 to 4): 4+
  • May cause nausea (combine with antiemetic); do not use within 24 hr of a triptan
  • Dose: 30–60 mg I.M.
• Corticosteroids: efficacy rating (on a scale of 0 to 4): 1+
  • Modest effect in preventing recurrence (number needed to treat is 9)
  • Prednisone
  • Dose: single or rapidly tapering dose, starting at 80 mg/day
• Dexamethasone
  • Dose: 6 mg p.o. or I.V.
• Meperidine: efficacy rating (on a scale of 0 to 4): 2+
  • May be combined with promethazine
  • Dose: 50–100 mg
• Valproate sodium: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 500 mg diluted in 50 ml saline I.V. over 5–10 min q. 8 hr
• Droperidol: efficacy rating (on a scale of 0 to 4): 4+
  • Rare risk of torsade de pointes
  • Dose: 2.5 mg I.M. or I.V.

• Consider daily preventive medication in the following circumstances:
  • Headaches significantly interfere with daily routine
  • Acute medications are contraindicated, ineffective, overused, or not tolerated
  • Migraines occur ≥ 2 times/wk
  • The cost is significantly less than that of acute treatment
• Principles of preventive treatment
  • Start with low dose and increase slowly
  • Give each drug a 2- to 3-mo trial
  • Discontinue or taper drugs that may be causing rebound headache
  • Patient should keep a record of headaches

• Beta blockers: side effects—hypotension, tiredness, depression
  • Propranolol: efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 40–120 mg b.i.d.
    • Cost/mo: $8
  • Long-acting propranolol
    • Dose: 60–160 mg/day
    • Cost/mo: $39
  • Metoprolol: efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 50–200 mg/day
    • Cost/mo: $39
  • Atenolol: efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 50–100 mg/day
    • Cost/mo: $4
  • Timolol: efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 10–30 mg/day
    • Cost/mo: $8
  • Nadolol: efficacy rating (on a scale of 0 to 4): 4+
    • Dose: 40–160 mg/day
    • Cost/mo: $13
• Antidepressants
  • Amitriptyline: efficacy rating (on a scale of 0 to 4): 4+
    • Anticholinergic side effects, weight gain
    • Dose: 25–150 mg h.s.
    • Cost/mo: $8
  • Nortriptyline: efficacy rating (on a scale of 0 to 4): 4+
    • Anticholinergic side effects, weight gain
    • Dose: 25–150 mg/day
    • Cost/mo: $10
  • Venlafaxine: efficacy rating (on a scale of 0 to 4): 4+ (anecdotal, not well studied)
    • Fewer side effects than tricyclics; weight-neutral
    • Dose: 75–150 mg XR/day
    • Cost/mo: $39
• Anticonvulsants
  • Divalproex sodium and ER: efficacy rating (on a scale of 0 to 4): 4+
    • Nausea, tremor, weight gain, alopecia, fetal anomalies
    • Dose: 500–1,000 mg/day
    • Cost/mo: $20
  • Topiramate: efficacy rating (on a scale of 0 to 4): 4+
    • Weight loss, paresthesias, cognitive effects, kidney stones (about 1%)
    • Dose: 50–300 mg h.s. (100 mg h.s. usual effective dose); start at 25 mg h.s. and increase by 25 mg/week
    • Cost/mo: $25
  • Gabapentin: efficacy rating (on a scale of 0 to 4): 2+
    • Dizziness, tiredness, drowsiness
    • Dose: 300–800 mg t.i.d.
    • Cost/mo: $69

Drugs for Tension Headache

• Acetaminophen: efficacy rating (on a scale of 0 to 4): 3+
  • Dose: 500 mg
• Aspirin: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 500–650 mg
• Ibuprofen: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 400–800 mg
• Acetaminophen + aspirin + caffeine: efficacy rating (on a scale of 0 to 4): 4+
  • Dose: 1–2 tablets q. 4 hr
• Isometheptene mucate: efficacy rating (on a scale of 0 to 4): 3+
  • Dose: 2 capsules at onset followed by 1 capsule q. 1 hr (max 5/24 hr)
• Butalbital 50 mg combination drugs: efficacy rating (on a scale of 0 to 4): 3+
  • Can lead to medication overuse headache and habituation
  • Dose: 1–2 q. 4 hr
• Muscle relaxants
  • Baclofen: Nonhabituating
    • Dose: 5–10 mg t.i.d., p.r.n.
  • Tizanidine: nonhabituating; monitor liver function for elevated transaminase
    • Dose: 2–4 mg t.i.d.

• Tricyclic antidepressants may be more effective than SSRIs

• Biofeedback, relaxation training, cognitive behavioral therapy
• Physical therapy for myofascial symptoms
• Trigger-point injection or occipital nerve block may help in some cases
• Preventive and symptomatic medications same as for migraine and tension headaches

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Best References

Evans RW (ed). Migraine and Other Primary Headaches. Neurol Clin 27:321-572, 2009 [PMID: 19289217]

Headache Classification Subcommittee of the International Headache Society: Cephalalgia 24(suppl 1):1, 2004 [PMID 14979299]

Silberstein SD, Lipton RB, Dodick DW: Wolff's Headache and Other Head Pain, 8th ed. Oxford University Press, New York, 2008