Practice Guidelines

AAFP/ACP-ASIM Release Guidelines on the Management and Prevention of Migraines



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Am Fam Physician. 2003 Mar 15;67(6):1392-1397.

The American Academy of Family Physicians (AAFP) and the American College of Physicians–American Society of Internal Medicine (ACP-ASIM), working jointly and with assistance from the American Headache Society, recently developed guidelines for primary care physicians on the pharmacologic management of acute migraine attacks and the prevention of migraines. The clinical guidelines were in the November 19, 2002, issue of Annals of Internal Medicine. The guidelines were based on articles by Matchar and associates and Ramadan and colleagues (available at www.aan.com/professionals/practice/guidelines.cfm) but contain somewhat different recommendations based on the levels of evidence needed to make a positive recommendation.

Diagnosis and Initial Management

Migraine is a primary headache disorder with a wide variety of manifestations. Recurrent acute attacks may not have the same characteristics in all patients or even in the same patient. Criteria for the diagnosis of migraine have been developed by the International Headache Society. However, physicians need to be aware that a patient can have more than one headache disorder (e.g., migraine and episodic tension-type headaches).

Patient Education and Involvement

Recommendation. The patient should be educated about the control of acute migraine attacks and preventive treatment. The patient should be involved in formulating a management plan. Regular reevaluation of therapy is important.

A discussion of the benefits and adverse effects of therapeutic options can help the patient establish realistic expectations. Together, the physician and patient should decide how acute attacks are to be treated and whether the patient would benefit from preventive medication.

Patient input is crucial to treatment selection and evaluation. Tracking progress with a daily flow sheet can be helpful in assessing treatment. The patient's headache diary should include the severity, frequency, and duration of migraine attacks; the degree of disability resulting from the attacks; the response to treatment; and adverse effects from medication. The patient also should be encouraged to identify factors or situations that trigger migraines (e.g., alcohol, caffeine, foods containing tyramine or nitrates, stress, fatigue, perfumes, fumes, glare, flickering lights).

Management of Acute Attacks

Management of acute migraine attacks needs to be individualized. Factors to consider include associated symptoms (e.g., nausea, vomiting), the frequency and severity of the attacks, and the degree of disability caused by the attacks. Comorbid conditions (e.g., uncontrolled hypertension, heart disease, pregnancy) and previous responses to specific medications may limit treatment options.

To guard against medication-overuse headaches, experts suggest limiting the use of acute treatment to no more than twice a week. Preventive migraine therapy should be considered if medication overuse is suspected or considered to be a risk.

Consideration should be given to the possibility of rebound headaches, which are associated with the withdrawal of analgesic drugs or abortive migraine medications. Although universal agreement is lacking, it is generally thought that rebound headaches can be caused by opiates, triptans, ergotamine, and analgesic medications that contain caffeine, isometheptene, or butalbital.

The physician may need to consider the patient's use of a rescue medicine (e.g., an opioid, a compound that contains butalbital) at home when other treatments for severe migraine attacks are not successful. Appropriate situations for use should be addressed.

Recommendation. In most patients with migraine, non-steroidal anti-inflammatory drugs (NSAIDs) are first-line treatment.

Evidence for efficacy is most consistent for these agents: aspirin, ibuprofen, naproxen sodium, tolfenamic acid (not currently available in the United States), and the acetaminophen-aspirin-caffeine combination. Acetaminophen alone is ineffective.

Recommendation. Migraine-specific agents (triptans, dihydroergotamine [DHE]) should be used in patients whose migraine attacks do not respond to NSAIDs.

Evidence for efficacy is good for the following triptans (serotonin1B/1D agonists): orally administered naratriptan, rizatriptan, and zolmitriptan, and orally and subcutaneously administered sumatriptan. Triptans should not be used in a patient who has uncontrolled hypertension or basilar or hemiplegic migraine or who is at risk for heart disease.

Evidence for efficacy and safety is good for intranasally administered DHE. There also is good evidence for the efficacy of butorphanol nasal spray. Treatment with opioids may be considered if other medications cannot be used and if the risk of abuse has been addressed and sedation is not a concern.

Recommendation. A nonoral route of administration should be selected when nausea or vomiting present early as significant components of migraine attacks. Nausea should be treated with an antiemetic drug.

Preventive Therapy

Numerous medications with varying efficacies are used to prevent migraines ( www.annals.org). Nonpharmacologic therapies also are used ( www.aan.com/professionals/practice/guidelines.cfm).

The AAFP/ACP-ASIM recommendations and the U.S. Headache Consortium recommendations are compared in the accompanying table.

Recommendation. The patient with migraine should be evaluated for the use of preventive treatment.

Commonly accepted indications for migraine prevention are as follows: two or more migraine attacks per month, with the attacks producing disability for three or more days per month; use of rescue medication more than twice a week; failure of acute treatments or contraindications for such treatments; or the presence of uncommon migraine conditions (e.g., prolonged aura, migrainous infarction, hemiplegic migraine). Additional factors that need to be considered include the patient's preference, adverse events with treatments for acute migraine attacks, and how much treatment costs for acute attacks and migraine prevention.

Recommendation. First-line agents for the prevention of migraines are as follows: propranolol, 80 to 240 mg per day; timolol, 20 to 30 mg per day; amitriptyline, 30 to 150 mg per day; divalproex sodium, 500 to 1,500 mg per day; and sodium valproate, 800 to 1,500 mg per day.

Some other drugs have been shown to be efficacious, but data on associated adverse events are limited. These agents include methysergide and a number of agents that currently are not available in the United States, including flunarizine, lisuride, pizotifen, and time-released DHE.

There is good evidence for the efficacy of propranolol and timolol. Common adverse effects of beta blockers, including dizziness, nausea, fatigue, depression, and insomnia, appear to be tolerated fairly well.

Summary of U.S. Headache Consortium Recommendations and the AAFP/ACP-ASIM Recommendations*

Treatment type U.S. Headache Consortium AAFP/ACP-ASIM

Acute

Use migraine-specific agents (triptans, DHE, ergotamine) in patients with severe migraine and in patients whose migraines respond poorly to NSAIDs or combination analgesics such as aspirin-acetaminophen-caffeine. Recommended medications based on at least two double-blind, placebo-controlled trials and clinical impression of effect: oral acetaminophen-aspirin-caffeine; oral aspirin; intranasal butorphanol; SC, IM, IV, or intranasal DHE; IV DHE plus an antiemetic; oral ibuprofen; oral naproxen sodium; oral naratriptan; IV prochlorperazine; oral rizatriptan; SC, intranasal, or oral sumatriptan; oral zolmitriptan

Use NSAIDs as first-line therapy. Recommended agents: aspirin, ibuprofen, naproxen sodium, tolfenamic acid, † acetaminophen-aspirin-caffeine

In patients whose migraines fail to respond to NSAIDs, use migraine-specific agents. Recommended agents: intranasal DHE, oral naratriptan, SC or oral sumatriptan, oral rizatriptan, oral zolmitriptan

Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex.

Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex. Treat nausea with an antiemetic.

Consider a self-administered rescue medication for patients with severe migraine that does not respond well to other treatments. ‡

Guard against medication-overuse headache.

Educate patients with migraine about their condition and its treatment, and encourage them to participate in their own management.

Educate patients with migraine about their condition and its treatment, and encourage them to participate in their own management.

Preventive

Medication use: initiate treatment with lowest effective dose; give each treatment an adequate trial; avoid interfering medications; use a long-acting formulation to improve adherence.

Patients with migraine should be evaluated for use of preventive therapy. Generally accepted indications for migraine prevention include (1) two or more attacks per month that produce disability that lasts three or more days per month, (2) contraindication to, or failure of, acute treatments, (3) use of abortive medication more than twice per week, or (4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction.

Recommended agents found to have medium to high efficacy and mild or infrequent side effects: amitriptyline, divalproex sodium, lisuride, † propranolol, timolol

Recommended first-line agents, currently available in the United States, for the prevention of migraine headache: propranolol, 80 to 240 mg per day; timolol, 20 to 30 mg per day; amitriptyline, 30 to 150 mg per day; divalproex sodium, 500 to 1,500 mg per day; sodium valproate, 800 to 1,500 mg per day

Recommended agents found to have medium to high efficacy but with side effect concerns: methysergide, flunarizine,† pizotifen, † time-released DHE†

Other medications with proven efficacy but limited published data on adverse events, or frequent or severe adverse events: flunarizine, † lisuride, † pizotifen, † time-released DHE, † methysergide

Recommended agents based on consensus and clinical experience: cyproheptadine, bupropion, diltiazem, doxepin, fluvoxamine, ibuprofen, imipramine, mirtazepine, nortriptyline, paroxetine, protriptyline, sertraline, tiagabine, topiramate, trazodone, venlafaxine

Patient education: maximize adherence; address patients' expectations; create a formal management plan

Educate patients with migraine about the control of acute attacks and preventive therapy, and engage them in the formulation of a management plan. Therapy should be reevaluated on a regular basis.

Evaluation: monitor patients' headaches by having them keep headache diaries; reevaluate therapy.

Encourage patients to be actively involved in their management by tracking their own progress through daily flow sheets, for example. Diaries should measure attack frequency, severity, duration, disability, response to type of treatment, and adverse effects of medication.

Comorbid conditions: once a comorbid condition is identified, select a pharmacologic agent that will treat both disorders; establish that the coexisting condition is not a contraindication to the selected migraine therapies and that the therapy will not exacerbate the migraine.


AAFP = American Academy of Family Physicians; ACP-ASIM = American College of Physicians–American Society of Internal Medicine; DHE = dihydroergotamine; NSAID = nonsteroidal anti-inflammatory drug; SC = subcutaneous; IM = intramuscular; IV = intravenous.

*— Consortium recommendations are based on published articles by Matchar and associates and Ramadan and colleagues (available at www.aan.com/professionals/practice/guidelines.cfm). The ACP-ASIM historically has not used a grading system for guideline recommendations because its development process mandates the use of only high-quality evidence (i.e., randomized controlled trials, or “A”-level evidence) as a basis for recommendations.

†— Currently not available in the United States.

‡— A rescue medication is an agent (e.g., opioid) that the patient can use at home when other treatments have failed.

Adapted with permission from Snow V, Weiss K, Wall EM, Mottur-Pilson C. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137:842–3.

Summary of U.S. Headache Consortium Recommendations and the AAFP/ACP-ASIM Recommendations*

View Table

Summary of U.S. Headache Consortium Recommendations and the AAFP/ACP-ASIM Recommendations*

Treatment type U.S. Headache Consortium AAFP/ACP-ASIM

Acute

Use migraine-specific agents (triptans, DHE, ergotamine) in patients with severe migraine and in patients whose migraines respond poorly to NSAIDs or combination analgesics such as aspirin-acetaminophen-caffeine. Recommended medications based on at least two double-blind, placebo-controlled trials and clinical impression of effect: oral acetaminophen-aspirin-caffeine; oral aspirin; intranasal butorphanol; SC, IM, IV, or intranasal DHE; IV DHE plus an antiemetic; oral ibuprofen; oral naproxen sodium; oral naratriptan; IV prochlorperazine; oral rizatriptan; SC, intranasal, or oral sumatriptan; oral zolmitriptan

Use NSAIDs as first-line therapy. Recommended agents: aspirin, ibuprofen, naproxen sodium, tolfenamic acid, † acetaminophen-aspirin-caffeine

In patients whose migraines fail to respond to NSAIDs, use migraine-specific agents. Recommended agents: intranasal DHE, oral naratriptan, SC or oral sumatriptan, oral rizatriptan, oral zolmitriptan

Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex.

Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex. Treat nausea with an antiemetic.

Consider a self-administered rescue medication for patients with severe migraine that does not respond well to other treatments. ‡

Guard against medication-overuse headache.

Educate patients with migraine about their condition and its treatment, and encourage them to participate in their own management.

Educate patients with migraine about their condition and its treatment, and encourage them to participate in their own management.

Preventive

Medication use: initiate treatment with lowest effective dose; give each treatment an adequate trial; avoid interfering medications; use a long-acting formulation to improve adherence.

Patients with migraine should be evaluated for use of preventive therapy. Generally accepted indications for migraine prevention include (1) two or more attacks per month that produce disability that lasts three or more days per month, (2) contraindication to, or failure of, acute treatments, (3) use of abortive medication more than twice per week, or (4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction.

Recommended agents found to have medium to high efficacy and mild or infrequent side effects: amitriptyline, divalproex sodium, lisuride, † propranolol, timolol

Recommended first-line agents, currently available in the United States, for the prevention of migraine headache: propranolol, 80 to 240 mg per day; timolol, 20 to 30 mg per day; amitriptyline, 30 to 150 mg per day; divalproex sodium, 500 to 1,500 mg per day; sodium valproate, 800 to 1,500 mg per day

Recommended agents found to have medium to high efficacy but with side effect concerns: methysergide, flunarizine,† pizotifen, † time-released DHE†

Other medications with proven efficacy but limited published data on adverse events, or frequent or severe adverse events: flunarizine, † lisuride, † pizotifen, † time-released DHE, † methysergide

Recommended agents based on consensus and clinical experience: cyproheptadine, bupropion, diltiazem, doxepin, fluvoxamine, ibuprofen, imipramine, mirtazepine, nortriptyline, paroxetine, protriptyline, sertraline, tiagabine, topiramate, trazodone, venlafaxine

Patient education: maximize adherence; address patients' expectations; create a formal management plan

Educate patients with migraine about the control of acute attacks and preventive therapy, and engage them in the formulation of a management plan. Therapy should be reevaluated on a regular basis.

Evaluation: monitor patients' headaches by having them keep headache diaries; reevaluate therapy.

Encourage patients to be actively involved in their management by tracking their own progress through daily flow sheets, for example. Diaries should measure attack frequency, severity, duration, disability, response to type of treatment, and adverse effects of medication.

Comorbid conditions: once a comorbid condition is identified, select a pharmacologic agent that will treat both disorders; establish that the coexisting condition is not a contraindication to the selected migraine therapies and that the therapy will not exacerbate the migraine.


AAFP = American Academy of Family Physicians; ACP-ASIM = American College of Physicians–American Society of Internal Medicine; DHE = dihydroergotamine; NSAID = nonsteroidal anti-inflammatory drug; SC = subcutaneous; IM = intramuscular; IV = intravenous.

*— Consortium recommendations are based on published articles by Matchar and associates and Ramadan and colleagues (available at www.aan.com/professionals/practice/guidelines.cfm). The ACP-ASIM historically has not used a grading system for guideline recommendations because its development process mandates the use of only high-quality evidence (i.e., randomized controlled trials, or “A”-level evidence) as a basis for recommendations.

†— Currently not available in the United States.

‡— A rescue medication is an agent (e.g., opioid) that the patient can use at home when other treatments have failed.

Adapted with permission from Snow V, Weiss K, Wall EM, Mottur-Pilson C. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137:842–3.

One comparative trial suggested that propranolol is superior in the patient with migraine alone, but that amitriptyline is more effective in the patient with mixed migraine and tension-type headache. Tricyclic antidepressants, including amitriptyline, can cause weight gain, drowsiness, and anticholinergic symptoms.

Evidence for efficacy is good for divalproex sodium and sodium valproate. These agents may be particularly effective in the patient who has prolonged or atypical migraine aura. Adverse effects can include hair loss, tremor, weight gain, and teratogenic effects (e.g., neural tube defects).

Once a drug for migraine prevention has been chosen, treatment should be initiated with a low dose. The dose should be increased slowly until benefits are achieved without adverse effects or are limited by adverse events. An adequate trial of the drug is important because clinical benefits may not become apparent for two to three months. After a period of stability, consideration can be given to tapering or discontinuing the drug.



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