• Recurrent headaches occur along with nausea/vomiting and/or photophobia and phonophobia.
• Each episode lasts 4 to 72 hours and usually ends with sleep.
• The headache has at least two of the classic features: it is unilateral, pulsating, moderate-to-severe intensity, and/or aggravated by movement.
• Five similar episodes must occur for diagnosis.
• No other condition better accounts for symptoms.
Acute Migraine Episodes
• Nonsteroidal antiinflammatory drugs (NSAIDs)
• Isometheptene-containing products
• Combination medications
• Tricyclic antidepressants
• Petasites (butterbur)7
7 Available as dietary supplement.
Migraines are episodic headaches accompanied by nausea and/or photophobia plus phonophobia. The headache must last 4 to 72 hours and have at least two defining features (it is unilateral, pulsating, moderate-to-severe intensity, and/or aggravated by movement). Five attacks and the exclusion of other conditions are required for diagnosis. Patients with migraine may also suffer from other types of headaches (e.g., tension).
About 45 million U.S. adults (18–23% of women, 6–9% of men) report migraine. Onset is usually between ages 12 and 30. Prevalence peaks in young adults. Migraine is diagnosed in about 30% of family medicine headache patients. A positive migraine diagnosis by a family physician is over 95% accurate, but cases may be misdiagnosed, especially as a tension or sinus headache.
Besides age and female sex, the biggest risk factor is family history.
Migraine results from complex interactions among multiple genetic and environmental factors. The primary neuronal process may be a depolarizing wave (Leão’s cortical spreading depression) activating the trigeminal nerve afferents and causing vasoactive neuropeptide release, local inflammation, vascular instability, and blood-brain barrier changes. The type and location of symptoms depend on which parts of the complex trigeminovascular system are activated. This system innervates pain-sensitive blood vessels and meninges and connects with various areas of the brain, including the thalamus and sensory cortex. Biochemically, serotonin, calcitonin gene-related peptide (CGRP), and other substances are implicated in migraine.
The suspected role of right–left cardiac shunts, especially patent foramen ovale, has not been validated.
The vulnerability to migraine cannot be eliminated, but patients can be assisted to reduce the number of attacks and minimize the negative impact of migraine through a consideration of triggers and use of prophylaxis.
Some migraineurs have specific precipitants for an attack. The strongest evidence is for stress, menstruation, missed meals, weather changes, and sleep disturbances. Migraines may be associated with stress or its relief (weekend migraine). Avoiding or minimizing triggers may reduce the likelihood of a migraine.
The U.S. Headache Consortium (USHC) and other guidelines recommend discussing prophylaxis with patients who meet the following criteria:
• They have severe and/or frequent symptoms that disrupt daily activities despite adequate treatment.
• They have a poor efficacy or inability to use standard treatments for acute attacks (e.g., because of adverse effects, contraindications, cost).
• They have specific rare migraine syndromes associated with dangerous neurologic complications (basilar migraine, prolonged aura, hemiplegic migraine).
Successful prophylaxis depends on balancing potential benefit against adverse effects and the demands of adherence to long-term medications. Selection of a prophylactic medication depends on patient factors (personal preferences, comorbidities such as hypertension and depression) and medication concerns (including efficacy, cost, pharmacokinetics, adverse effects, and medication interactions).
Prophylactic medication should be started at a low dose and gradually increased until benefit is demonstrated or adverse effects outweigh benefits. Individual patients show enormous variation in the effective dose of prophylactic medication. An adequate trial of prophylaxis requires several months. A patient may have poor outcomes from one agent but good response to an agent from a different class. A headache diary is useful to monitor symptoms and adverse effects. Therapy should be reevaluated every 3 to 6 months.
The USHC evidence-based recommendations for migraine prophylaxis based on efficacy and potential adverse effects have been updated by the American Academy of Neurology (AAN) (Table 1).
The AAN (2012) and European (2009) guidelines confirm the use of certain beta-blockers and antiepileptic medications and also for the first time rate herbal and complementary treatments. Level A evidence was established for petasites (butterbur extract)7 50 to 75 mg twice daily. Magnesium (400–600 mg),1 feverfew7 (as MIG-99 extract, 6.25 mg three times daily), and riboflavin7 (400 mg) were classified as level B. Coenzyme Q107 (100 mg tid) was classified as level C and omega-37 (3 g twice daily) as level U.
Medications for Migraine Prophylaxis
Sources: 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;78:1337–1345; Silberstein SD, Holland S, 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;78:1346–1353. Dosages from Becker WJ, Gawel M, Mackie G, et al. Migraine treatment. Can J Neurol Sci 2007;34:S10–19 and Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine: Revised report of an EFNS task force. Eur J Neuro 2009;16:968–981; Ramadan NM, Silberstein SD, Freitag F, Gilbert TT, Frishberg BM. Evidence-based guidelines for migraine headache in the primary care setting: Pharmacological management for prevention of migraine. U.S. Headache Consortium, 2000. Available at www.aan.com/professional/practice.
1 Not FDA approved for this indication.
2 Exceeds dosage recommended by the manufacturer.
3 Available as dietary supplement.
4 Not available in the United States.
* Short-term use only.
† Dosage not established.
Nondrug therapies to prevent attacks may be preferred by some patients, including those who have had limited success with medications. The four main types of nonpharmacologic therapies are relaxation training, biofeedback therapy, cognitive-behavioral training (stress-management training), and physical treatments (acupuncture, cervical manipulation, and mobilization therapy). Each may be used alone or in combination with other therapies, including medications.
Research evidence is lacking or controversial for many of these therapies. The USHC concluded that relaxation training, thermal biofeedback combined with relaxation training, and cognitive- behavioral therapy are all modestly effective in preventing migraine (Grade A); behavioral therapy (relaxation, biofeedback) combined with preventive drug therapy (propranolol [Inderal], amitriptyline [Elavil]1) may provide additional clinical improvement (Grade B); but no recommendations could be made for hypnosis, acupuncture, transcutaneous electric neuromuscular stimulation, cervical manipulation, occlusal adjustment, and hyperbaric oxygen as preventive or acute therapy for migraine.
Prodrome: About 60% of migraineurs experience 1 to 2 days of symptoms such as yawning, intense hunger, mild euphoria, or depression/irritability before an attack.
About 25% of migraineurs report consistent, specific neurologic changes about 5 to 60 minutes before the onset of headache. Common aura symptoms include visual (flashing lights, zigzag lines, scotoma), sensory (paresthesia, numbness), or speech disturbances.
Migraine combines a specific type of headache (unilateral, throbbing, moderate-to-severe, worse with activity) with other diagnostic symptoms (nausea/vomiting and/or photophobia/phonophobia).
Many patients also experience vertigo, allodynia, and fatigue. Additional symptoms may be prominent in migraine subtypes such as basilar or ophthalmoplegic migraine. Patients vary enormously in the symptom pattern as well as in the frequency, intensity, and impact of attacks. Some have infrequent episodes with mild symptoms, whereas others are incapacitated by recurrent, severe attacks.
Duration and Complications
Classically, migraine patients lie still in a dark room until sleep resolves symptoms. Afterward, some patients feel refreshed, others are tired, and others experience localized skull tenderness or headache on movement.
Status migrainosus is debilitating migraine lasting more than 72 hours. The patient may be dehydrated, exhausted, and/or suffering adverse medication effects. Very rarely, migraine subtypes (basilar, ophthalmoplegic, hemiplegic) are complicated by seizure or cerebral infarction. Chronic migraine (defined as symptoms on more than 15 days per month) requires investigation, especially for medication- rebound headache. With inappropriate therapy, migraine can transform into chronic daily headache.
Migraine diagnosis depends on history. Identifying classic symptoms has a high probability of accurate diagnosis (Table 2). The headache pattern should distinguish migraine from other primary headaches (e.g., tension, cluster). The clinical history and examination target identifying conditions that could cause secondary headache.
Neurologic examination must be documented, because change over time is crucial in detecting the rare cases of intracranial pathology that present with migraine-type symptoms.
Diagnostic Probability of Symptoms for Migraine (POUND Mnemonic)
|Character of headache described as pulsing or throbbing Duration average One day (4–72 h)
Associated symptoms include Nausea or Vomiting Severity ranked as disabling
Probability of migraine 92% with 4 POUND symptoms, 64% with 3, 17% with 0–2.
|From Gilmore and Michael (2011).|
Diagnostic imaging is not indicated in migraine patients with normal neurologic examination. Guidelines recommended imaging only for atypical symptoms or “red flag” indications of serious
pathology but recognize that some patients may require testing for excessive anxiety (Table 3). Other testing (e.g., complete blood count, sedimentation rate, analysis of cerebrospinal fluid) are selected to identify specific potential causes of symptoms in individual patients. Guidelines stress that testing should be done only if results are likely to change management.
“Red Flag” Findings Associated with Increased Risk of Underlying Pathology in Headache
Age greater than 55 years
Associated symptoms (fever, neurologic symptoms, mental status changes)
Abnormal neurologic examination
|Adapted from Silberstein (2000).
Notes: Headache type, severity, characteristics, or duration were not risk factors; increasing frequency and headache awakening from sleep were positively associated. In the ER setting, patients over 50 years of age with acute onset and neurologic signs had 98.6% specificity for serious intracranial pathology.
Other recurrent headaches, especially tension or cluster, can usually be distinguished by the combination of features (unilaterality, nausea, photo/phonophobia) and pattern (frequency of occurrence and duration).
Intracranial pathology (including acute or chronic bleeding, infection, or space-occupying lesions) can cause headache resembling migraine. This can also occur with head and neck conditions such as temporal arteritis, sinusitis, temporomandibular joint syndrome, and various neuralgias as well as systemic conditions including carbon monoxide poisoning, sudden rise in blood pressure, or medication adverse effect. Diagnosis depends on recognizing that the clinical picture is not completely congruent with migraine, and also on identifying risk factors, symptoms, and signs, along with positive targeted testing for the underlying condition.
Treatment goals for acute migraine are rapid symptom control, minimizing adverse effects, preventing recurrence, and optimizing function. Self-management and efficient use of resources are priorities. The USHC guidelines (2000) and more recent European guidelines (2009) are based on research evidence. Individual patients vary enormously in response to specific medications and in the effective dose. Patients who do not respond to an appropriate dose of one medication may have good outcomes from another agent in the same class or one from a different class. Medications should be taken in adequate dosage as early as possible during a migraine attack.
Nonoral formats or adjunct medications may be necessary because of vomiting or poor absorption resulting from gastric stasis.
Many medications have antimigraine activity (Table 4).
Considerations in selecting an agent include patient comorbidities (e.g., hypertension) and the medication’s potential adverse effects. Cost may be a significant concern.
Medications for Treatment of Acute Migraine
1 Not FDA approved for this indication.
* Doses < 1000 mg in combination with antiemetics and other agents in studies.
† Not included in U.S. Headache Consortium Guidelines, 2000.
Of first-line therapies, NSAIDs or combination analgesics with caffeine are recommended for mild-to-moderate attacks or more severe attacks that have previously responded to these agents.
Evidence also supports intramuscular ketorolac (Toradol)1 as a useful strategy for vomiting patients.
Triptans are recommended for moderate-to-severe migraine and for mild-to-severe attacks that have not responded adequately to other first-line therapies. Individual triptans have comparable efficacy and tolerability but differ in speed of onset and duration of action. This allows for the selection of an agent with pharmacokinetics that correspond to the patient’s migraine symptom pattern. The most effective agent and dose for each patient can only be established by experience. Triptans may be combined synergistically with NSAIDs.
Potential triptan adverse effects include vasoconstriction and serotonin syndrome.
Ergotamines are effective in migraine but limited by adverse effects, especially vasoconstriction. They are less effective than triptans but may have good results in some patients. Nasal spray is useful if the patient cannot take oral medications. In emergency room studies, parenteral dihydroergotamine (D.H.E. 45) combined with antiemetics has been as effective as opiates. Opiates are rarely appropriate for migraine. Studies show that other agents are more effective with fewer adverse effects and no risk of addiction or exploitation.
An estimated 3% of migraine sufferers progress to develop chronic migraine each year. Chronic migraine is defined as at least three months of headache on 15 or more days per month with headaches fulfilling criteria for migraine on at least eight days per month. Other causes of symptoms, including medication overuse, must be excluded for diagnosis of chronic migraine. Persistent changes in brain structure and function occur in chronic migraine resulting in central sensitization, intractable symptoms and vulnerability to psychiatric comorbidities. Treatment requires lifestyle modification, consideration of non-pharmacological therapies (biofeedback, cognitive behavioral therapy, physical therapy, relaxation therapy or acupuncture), management of symptoms, and prophylactic therapy. The only currently approved prophylactic treatments specifically for chronic migraine are onabotulinumtoxin A (Botox) and topiramate (Topamax)1 but other prophylactic therapies may reduce the frequency and impact of recurrent migraine headaches in patients with chronic migraine.
Regular monitoring can allow for the adjustment of medication for maximum efficacy and minimal adverse effects, promote healthy lifestyles, and aid in screening for migraine comorbidities, especially depression. Conversion to chronic daily headache by overuse of medications is a major concern.
1. Aurora S.K., Brin M.F. Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Headache 20. 2017;57:109–125.
2. Gilmore B., Michael M. Treatment of acute migraine headache. Am Fam Physician. 2011;83:271–280.
3. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgia, and facial pain. Cephalalgia. 1988;8:1–96.
4. International Classification of Headache Disorders. 3rd edition (beta version). Cephalalgia. 2013;33(9):629–808.
5. Lipton R.B., Stewart W.F., Diamond S., et al. Prevalence and burden of migraine in the United States: Data from the American Migraine Study II. Headache. 2001;41:646–657.
6. Loder E., Burch R., Rizzoli P. The 2012 AHS/AAN Guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache. 2012;52:930–945.
7. Marmura M.J., Silberstein S.D., Schwedt T.J. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies.Headache. 2015;55:3–20.
8. Stokes M., Becker W.J. Lipton RB et al. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS), Headache. 2011;51:1056–1077.
9. Silberstein S.D. Practice parameter: Evidence-based guidelines for migraine headache (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754–762.
1 Not FDA approved for this indication.
1 Not FDA approved for this indication.