The U.S. Headache Consortium guidelines on the pharmacologic management of acute migraine include recommendations for individual drugs. The recommendations are based on scientific evidence and on clinical opinion. Because few clinical trials have head-to-head comparisons of different agents, the consortium could not develop recommendations that specify the use of one agent over another. Similarly, the lack of sufficient data did not allow construction of an algorithmic approach to the selection of drug therapy for acute migraine. The second part of the migraine guidelines, published in the October 15, 2000 issue of American Family Physician, contained a table that grouped the various drugs used in the treatment of acute migraine according to the strength of the evidence for clinical benefit. In this issue, the specific recommendations for individual drugs are described. 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 (https://www.aafp.org).

The headache consortium evaluated data from many clinical studies and developed efficacy and safety profiles of each drug. Three categories (Grade A, Grade B and Grade C) were used to measure the quality of the evidence for clinical efficacy of the different drugs and doses. In addition, consortium participants rated the efficacy and adverse effects on the basis of the results of randomized controlled trials and on consensus of the U.S. Headache Consortium. The accompanying table summarizes findings on efficacy and safety of the various drugs used in the treatment of acute migraine.

Specific Recommendations for Individual Drugs

The following is an excerpt of the section in the migraine guidelines that outlines the findings from clinical studies and the specific recommendations for individual drugs. Definitions for the three classes of recommendations (Grades A, B and C) are at the bottom of the table on page 2146.

• Oral antiemetics in general—Findings: Studies of specific agents, such as domperidone and prochlorperazine, suggest some clinical benefit, but studies are limited. No studies were identified for other oral antiemetics as monotherapy to manage acute migraine attacks.

  Recommendation: Oral antiemetics may be used as an adjunct in the treatment of nausea associated with migraine (Grade C recommendation).

• Intramuscular (IM) metoclopramide—Findings: Studies did not demonstrate efficacy as monotherapy for the treatment of acute migraine.

  Recommendation: IM metoclopramide may be considered as an adjunct to control nausea in the treatment of migraine (Grade C recommendation).

• Intravenous (IV) metoclopramide—Findings: Two out of three studies reported that IV metoclopramide is effective for the acute treatment of migraine.

  Recommendation: IV metoclopramide may be an appropriate choice as adjunct therapy for the treatment of pain or nausea in the appropriate setting (Grade C recommendation). It may be considered as monotherapy for migraine pain relief (Grade B recommendation).

• Parenteral prochlorperazine—Findings: One study each evaluated the efficacy of prochlorperazine IM, IV and rectally and found it to be relatively safe and effective for the treatment of migraine headache and associated nausea and vomiting.

  Recommendation: Prochlorperazine IM, IV and rectally may be a therapeutic choice for migraine in the appropriate setting (Grade B recommendation). Prochlorperazine rectally may be considered an adjunct in the treatment of acute migraine with nausea and vomiting (Grade C recommendation).

• Serotonin receptor (5-HT3) antagonists—Findings: Studies of the efficacy of granisetron and zatosetron (not currently available in the United States) did not demonstrate a statistically significant clinical benefit for headache relief. Sufficient studies have not been done to demonstrate the clinical efficacy of this class of drug.

  Recommendation: Evidence is insufficient to establish or refute a role for 5-HT₃ antagonists as monotherapy in the management of acute attacks (Grade B recommendation). However, 5-HT₃ antagonists may be considered as adjunct therapy to control nausea in select patients with migraine attacks (Grade C recommendation).

• Butalbital-containing agents—Findings: No randomized, placebo-controlled studies prove or refute efficacy of butalbital-containing agents in the treatment of acute migraine headaches.

  Recommendation: Based on concerns of overuse, medication-overuse headache and withdrawal, the use of butalbital-containing analgesics should be limited and carefully monitored (Grade B recommendation).

• Oral and rectal ergotamine (and caffeine combination)—Findings: Evidence is inconsistent to support efficacy of ergotamine for the treatment of migraine. Studies documented a higher incidence of adverse events with ergots as compared with placebo, sumatriptan, isometheptene, nonsteroidal anti-inflammatory drugs (NSAIDs) or dextropropoxyphene compounds.

  Recommendation: In the treatment of select patients with moderate to severe migraine, ergot derivatives may be considered (Grade B recommendation).

• Subcutaneous (SC), IV and IM dihydroergotamine (DHE)—Findings: No placebo-controlled trials in migraine patients have demonstrated efficacy and safety as monotherapy. Clinical opinion suggests that SC DHE is relatively safe and effective when compared with other migraine therapies and that SC DHE has fewer adverse events than IV DHE.

  Recommendation: Because of their inability to tolerate or take oral medication, patients with nausea and vomiting may be given SC, IV or IM DHE (Grade C recommendation). Initial treatment with SC or IM DHE is a reasonable choice when the headache is moderate to severe or when an adequate trial of NSAIDs or other nonopiate analgesics, including combination analgesics such as acetaminophen plus aspirin plus caffeine, has failed to provide adequate relief in the past (Grade C recommendation). The use of IM or SC DHE may be considered in patients with moderate to severe migraine (Grade B recommendation).

• IV DHE plus IV antiemetic—Findings: The combination of IV DHE and antiemetic has been shown to be effective and moderately safe in the treatment of moderate to severe migraine as compared with parenteral opiates.

  Recommendation: IV DHE plus antiemetics is an appropriate treatment choice for patients with severe migraine (Grade B recommendation).

• DHE nasal spray—Findings: DHE nasal spray is safe and effective for the treatment of acute migraine attacks.

  Recommendation: DHE nasal spray is an appropriate treatment choice and should be considered for use in patients with moderate to severe migraine (Grade A recommendation). Because of their inability to tolerate or take oral medications, patients with nausea and vomiting may be given intranasal DHE (Grade C recommendation). Initial treatment with DHE nasal spray is a reasonable choice when the headache is moderate to severe or when an adequate trial of NSAIDs or other nonopiate analgesics, including combination analgesics such as acetaminophen plus aspirin plus caffeine, has failed to provide adequate relief in the past (Grade C recommendation).

• Acetaminophen—Findings: No evidence establishes the efficacy of acetaminophen in the acute treatment of migraine.

  Recommendation: Acetaminophen is not a specific treatment option for migraine (Grade B recommendation).

• Oral NSAIDs and combination analgesics in general—Findings: The most consistent evidence exists for aspirin, ibuprofen, naproxen sodium, tolfenamic acid (not currently available in the United States) and the combination agent acetaminophen plus aspirin plus caffeine. Limited (only one study) or inconsistent (some positive and some negative) evidence exists for other NSAIDs.

  Recommendation: Their favorable tolerability makes these agents a reasonable first-line treatment choice for mild to moderate migraine attacks or severe attacks that have been responsive in the past to similar NSAIDs or nonopiate analgesics (Grade A recommendation).

• IM ketorolac—Findings: No placebo-controlled trials testing the efficacy of IM ketorolac for the treatment of acute migraine attack have been published. Small comparative trials suggest possible equivalence to some agents, and a single comparison trial with meperidine demonstrated inferiority.

  Recommendation: IM ketorolac is an option that may be used in a physician-supervised setting, although conclusions regarding clinical efficacy cannot be made at this time (Grade C recommendation).

• Butorphanol nasal spray—Findings: The clinical efficacy of butorphanol specifically for migraine has been documented in two published reports.

  Recommendation: Clinical experience and expert consensus concur that butorphanol represents a treatment option for some patients with migraine (Grade A recommendation). Specifically, butorphanol may be considered when other medications cannot be used or as a rescue medication when significant sedation would not jeopardize the patient (Grade C recommendation). Clinical concerns regarding the use of butorphanol lie in the fact that it is widely used despite the established risk of overuse and dependence. In certain patients for whom use might be indicated, special attention should be given to these clinical concerns.

• Oral combination opiates—Findings: Studies demonstrate the effectiveness of oral opiate combination agents in terms of pain relief.

  Recommendation: Oral opiate combinations may be considered for use in acute migraine when sedation side effects will not put the patient at risk and/or the risk for abuse has been addressed (Grade A recommendation).

• IM and IV opiates—Findings: Only one placebo-controlled study has been published for IM methadone and IM meperidine. This study demonstrated the effectiveness of opiates for pain relief.

  Recommendation: Parenteral opiates may be considered for rescue therapy in a supervised setting when sedation side effects will not put the patient at risk and when the risk of abuse has been addressed (Grade B recommendation).

• Serotonin receptor agonists, or “triptans”—Findings: These agents (naratriptan, rizatriptan, sumatriptan and zolmitriptan) are effective and relatively safe for the acute treatment of migraine headaches. No evidence supports their use during the aura phase of an attack. (Published case reports of cardiovascular ischemic events with this class of drug are found in the literature and are included in the product label.)

  Recommendation: The triptans are an appropriate treatment choice and may be considered for use in patients with moderate to severe migraine who have no contraindications to their use (Grade A recommendation). Because of their inability to take oral medications, patients with nausea and vomiting may be given intranasal or SC sumatriptan (Grade C recommendation). Migraine-specific agents (triptans, DHE, ergotamine) should be used 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 (Grade C recommendation).

• Isometheptene and isometheptene-combination agents—Findings: Isometheptene-containing compounds are superior to placebo, with a small but statistically significant effect.

  Recommendation: Based on clinical evidence and favorable tolerability, isometheptene-containing compounds may be a reasonable choice for patients with mild to moderate headache (Grade B recommendation).

• Dexamethasone or hydrocortisone—Findings: No studies of good quality support or refute the effectiveness of steroids for acute migraine.

  Recommendation: Corticosteroids may be considered as a treatment choice for rescue therapy in patients with status migrainosus (Grade C recommendation).

• Intranasal and IV lidocaine—Findings: Limited studies of intranasal lidocaine reported lidocaine to be superior to placebo in relieving acute migraine headache at 15 minutes. Mixed results have been reported in the incidence of recurrence. A few small studies suggest that IV lidocaine is not significantly better than placebo and is less effective than other parenteral therapies for the treatment of acute migraine.

  Recommendation: Evidence is insufficient at this time to establish a defined role for intranasal lidocaine in the management of acute migraine (Grade B recommendation). Evidence is insufficient to support the role of IV lidocaine in the management of acute migraine (Grade B recommendation).