Practice Guidelines

Guidelines on Migraine: Part 2. General Principles of Drug Therapy



FREE PREVIEW Log in or buy this issue to read the full article. AAFP members and paid subscribers get free access to all articles. Subscribe now.


FREE PREVIEW Subscribe or buy this issue. AAFP members and paid subscribers get free access to all articles.

Am Fam Physician. 2000 Oct 15;62(8):1915-1917.

The U.S. Headache Consortium guidelines on the pharmacologic management of acute migraine emphasize the need for physicians and patients to work together to decide how to treat acute attacks. The panel members identified six goals for the long-term treatment of migraine: (1) reduce the frequency and severity of attacks; (2) reduce disability from the attacks; (3) improve the patient's quality of life; (4) prevent headache; (5) avoid escalation of medication used to treat migraine; and (6) educate patients and enable them to manage their headaches. The panel members also identified six goals for the treatment of acute attacks: (1) treat the attacks rapidly and consistently and eliminate recurrence of the attack; (2) restore the patient's ability to function; (3) minimize the use of backup and rescue medications; (4) optimize self-care and reduce subsequent use of resources; (5) institute cost-effective approaches for overall management; and (6) minimize or avoid adverse events. The guidelines are available at the American Academy of Neurology Web site (http://www.neurology.org) and at the American Academy of Family Physicians Web site (http://www.aafp.org).

To develop evidence-based recommendations for the pharmacologic treatment of acute migraine attacks, members of the headache consortium reviewed the migraine guidelines of the Agency for Healthcare Research and Quality (formerly the Agency for Health Care Policy and Research) as well as an analysis by the Duke University Center for Clinical Health Policy Research, Durham, N.C. Panel members analyzed data from many clinical studies of drugs used to treat acute migraine, including antiemetics, barbiturate hypnotics, ergot alkaloids and derivatives, nonsteroidal anti-inflammatory drugs (NSAIDs), combination analgesics, nonopiate analgesics, opiate analgesics and serotonin 5-HT agonists (i.e., the “triptans”). The accompanying table on page 1916 provides a breakdown of the various drugs used in the treatment of acute migraine and the strength of the evidence for their use. A summary of the headache consortium's recommendations for individual drugs will be published in the next issue of American Family Physician.

Strength of the Evidence for Clinical Benefits of Specific Drugs Used in the Treatment of Acute Migraine

Group 1: Proven pronounced statistical and clinical benefit, on the basis of at least two double-blind, placebo-controlled studies plus clinical impression of effect

Acetaminophen plus aspirin plus caffeine, orally

Aspirin, orally

Butorphanol, IN

Dihydroergotamine, SC, IM, IV

Dihydroergotamine, IV plus antiemetic

Dihydroergotamine, IN

Ibuprofen, orally

Naproxen sodium, orally

Naratriptan, orally

Prochlorperazine, IV

Rizatriptan, orally

Sumatriptan, SC, IN, orally

Zolmitriptan, orally

Group 2: Moderate statistical and clinical benefit, on the basis of one double-blind, placebo-controlled study plus clinical impression of effect

Acetaminophen plus codeine, orally

Butalbital plus aspirin plus caffeine plus codeine, orally

Butorphanol, IM

Chlorpromazine, IM, IV

Diclofenac-K, orally

Ergotamine plus caffeine plus pentobarbital plus bellafoline, orally

Flurbiprofen, orally

Isometheptene compound, orally

Ketorolac, IM

Lidocaine, IN

Meperidine, IM, IV

Methadone, IM

Metoclopramide, IV

Naproxen, orally

Prochlorperazine, IM, rectally

Group 3: Statistically effective but not proven clinically effective OR clinically effective but not proven statistically effective, on the basis of conflicting or inconsistent evidence

Butalbital plus aspirin plus caffeine, orally

Ergotamine, orally

Ergotamine plus caffeine, orally

Metoclopramide, IM, rectally

Group 4: Proven to be statistically or clinically ineffective, on the basis of failed efficacy versus placebo

Acetaminophen, orally

Chlorpromazine, IM

Granisetron, IV

Lidocaine, IV

Group 5: Clinical and statistical benefits unknown, on the basis of insufficient evidence available

Dexamethasone, IV

Hydrocortisone, IV


IM = intramuscularly; IN = intranasally; IV = intravenously; SC = subcutaneously.

Reprinted with permission from Matchar DB, Young WB, Rosenberg JH, Pietrzak MP, Silberstein SD, Lipton RB, et al. U.S. Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. Copyright by the American Academy of Neurology.

Strength of the Evidence for Clinical Benefits of Specific Drugs Used in the Treatment of Acute Migraine

View Table

Strength of the Evidence for Clinical Benefits of Specific Drugs Used in the Treatment of Acute Migraine

Group 1: Proven pronounced statistical and clinical benefit, on the basis of at least two double-blind, placebo-controlled studies plus clinical impression of effect

Acetaminophen plus aspirin plus caffeine, orally

Aspirin, orally

Butorphanol, IN

Dihydroergotamine, SC, IM, IV

Dihydroergotamine, IV plus antiemetic

Dihydroergotamine, IN

Ibuprofen, orally

Naproxen sodium, orally

Naratriptan, orally

Prochlorperazine, IV

Rizatriptan, orally

Sumatriptan, SC, IN, orally

Zolmitriptan, orally

Group 2: Moderate statistical and clinical benefit, on the basis of one double-blind, placebo-controlled study plus clinical impression of effect

Acetaminophen plus codeine, orally

Butalbital plus aspirin plus caffeine plus codeine, orally

Butorphanol, IM

Chlorpromazine, IM, IV

Diclofenac-K, orally

Ergotamine plus caffeine plus pentobarbital plus bellafoline, orally

Flurbiprofen, orally

Isometheptene compound, orally

Ketorolac, IM

Lidocaine, IN

Meperidine, IM, IV

Methadone, IM

Metoclopramide, IV

Naproxen, orally

Prochlorperazine, IM, rectally

Group 3: Statistically effective but not proven clinically effective OR clinically effective but not proven statistically effective, on the basis of conflicting or inconsistent evidence

Butalbital plus aspirin plus caffeine, orally

Ergotamine, orally

Ergotamine plus caffeine, orally

Metoclopramide, IM, rectally

Group 4: Proven to be statistically or clinically ineffective, on the basis of failed efficacy versus placebo

Acetaminophen, orally

Chlorpromazine, IM

Granisetron, IV

Lidocaine, IV

Group 5: Clinical and statistical benefits unknown, on the basis of insufficient evidence available

Dexamethasone, IV

Hydrocortisone, IV


IM = intramuscularly; IN = intranasally; IV = intravenously; SC = subcutaneously.

Reprinted with permission from Matchar DB, Young WB, Rosenberg JH, Pietrzak MP, Silberstein SD, Lipton RB, et al. U.S. Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. Copyright by the American Academy of Neurology.

General Principles of Management

The U.S. Headache Consortium identified two general principles of care for patients with migraine: (1) involve patients in their own management, such as discussing preferences for treatment, and (2) tailor treatment to the individual patient's needs, such as according to the severity of the migraines, comorbidity, coexisting conditions and previous response to medications.

Five general recommendations for the treatment of acute migraine were formulated by the headache consortium:

  • Educate patients with migraine about their condition and its treatment and encourage them to participate in their own management. According to the guidelines, the patient's input can provide the best guide to the selection of treatment, in part because patients differ in their response to individual agents. In addition, by obtaining the patient's input, the physician can better understand and accommodate the patient's goals of treatment. Because strategies for treating acute migraine attacks can be complex, the patient is more likely to achieve success if he or she is engaged in developing the treatment plan.

  • Use migraine-specific agents in patients with more severe migraine and in those whose headaches respond poorly to NSAIDs or combination analgesics such as aspirin plus acetaminophen plus caffeine. The consortium members believe that clinical experience strongly indicates that headaches of different types and severity respond to specific agents, even though no data support this impression.

  • Select a nonoral route of administration for patients whose migraines are characterized by nausea or vomiting early in the course of an attack. The guidelines state that an antiemetic should not be limited to patients who have vomiting or who are likely to vomit because nausea is one of the most disabling symptoms of a migraine attack. The combination of an antiemetic and an oral migraine drug may be appropriate in some patients.

  • Consider use of a self-administered rescue medication for patients with severe migraines that fail to respond well to other treatments. A rescue medication is used at home when other migraine treatments fail to provide relief. While a rescue medication may not completely eliminate the pain, it can provide relief and obviate the need for the patient to visit the physician's office or the emergency department.

  • Guard against medication-overuse headache. Medication-overuse headache, sometimes referred to as “rebound headache” or “drug-induced headache,” is characterized by an increased frequency in the headaches, to as often as daily. The guidelines state that rebound headache is different from medication-overuse headache. Rebound headache is associated with withdrawal of analgesics or of medications used to abort migraine attacks. The consortium found that there is no agreement concerning which agents can cause rebound headache. In general, this phenomenon is thought to occur with ergotamine, opiates, serotonin 5-HT agonists, NSAIDs and analgesics containing butalbital, caffeine or isometheptene. To decrease the risk of medication-overuse headaches, the consortium members point out that many experts suggest that acute therapy be reserved for those patients who regularly have two or more headache days per week. Preventive therapy may be considered in patients suspected of medication overuse or at risk of overuse.

Questions to Be Answered by Future Research

The U.S. Headache Consortium identified a number of aspects of migraine treatment that require research. For example, among the unanswered questions are whether it is effective to target therapy to headache severity and whether early aggressive therapy provides significant benefit in less severe migraine or migraine prodrome. Studies are also needed to identify the etiology of headache recurrence and measures that can be taken to avoid it and to treat it. Research is also needed to identify any factors, including specific agents and dosages, that may increase the susceptibility to rebound headache. While rescue medications are often used in the management of migraine, clinical studies are needed to clarify which patients are likely to benefit from this approach.

With regard to specific agents used in the treatment of migraine, the consortium members found that long-term studies are needed to evaluate the efficacy of opiate analgesics in reducing the frequency, severity and duration of migraine attacks. They also found that no randomized, placebo-controlled trials have been performed to evaluate the efficacy of butalbital-containing analgesics in the treatment of migraine, despite their widespread use.


This is the second of a five-part series summarizing the U.S. Headache Consortium guidelines on migraine. The first part, on the use of diagnostic imaging in nonacute headache, appeared in the October 1, 2000 issue of American Family Physician. The third part, on recommendations for specific drugs, will appear in the next issue. Participants in the consortium included the American Academy of Neurology, the American Academy of Family Physicians, the American Headache Society, the American College of Emergency Physicians, American College of Physicians–American Society of Internal Medicine, American Osteopathic Association and the National Headache Foundation.

The evidence-based guidelines for migraine headache were supported by: Abbott Laboratories, AstraZeneca, Bristol Myers Squibb, Glaxo Wellcome, Merck, Pfizer, Ortho-McNeil and the AAN Education and Research Foundation, along with the seven participant member organizations.


Copyright © 2000 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


Article Tools

  • Print page
  • Share this page
  • AFP CME Quiz

Information From Industry

More in Pubmed

Navigate this Article