American College of Physicians: Internal Medicine — Doctors for Adults ®


Drug therapies to treat—and prevent—migraines

From the July-August ACP-ASIM Observer, copyright 2002 by the American College of Physicians-American Society of Internal Medicine.

By Jason van Steenburgh

Is it really a migraine?
A summary of drugs to treat acute migraine headaches

PHILADELPHIA-If you're like many physicians, you probably tell patients suffering from migraine headaches to try ibuprofin before you prescribe something stronger.

But by the time they come to you for help, most patients have already tried nonsteroidal anti-inflammatory drugs (NSAIDs), according to panelists at an Annual Session presentation on migraines. If you tell them to do something so obvious, the panelists said, you'll only frustrate patients—and possibly lose them to specialists.

While it's true that NSAIDs are the first line of defense in treating migraines, experts say that you should consider using other drugs, particularly when one class of agents isn't working. Even more importantly, you need to tell patients that NSAIDs are only the first part of your strategy to treat their migraines.

To give patients relief from the pain, nausea and light sensitivity of migraines, physicians can offer a multi-tiered regimen of drugs.


When evaluating how well migraine medications are working, consider how fast patients feel relief, and whether they are pain free after two hours. When initial drugs don't work and you need to turn to rescue medications, pay particular attention to how often you use those drugs to treat recurrences in the two to 24 hours that follow.

Here is an overview of drugs to consider:

  • First-line treatments. Because they produce relatively few side effects, NSAIDs are a good place to start. David B. Matchar, FACP, director and professor of medicine at Duke University Center for Clinical Health Policy Research in Durham, N.C., said research has shown that NSAIDs like ibuprofen and naproxen, as well as analgesics like aspirin, can be effective in treating migraines. He also noted that agents that combine acetaminophen, aspirin and caffeine, such as Excedrin Migraine, also work for some patients.

    Dr. Matchar said, however, that NSAIDs help only a limited group of patients. He pointed out that studies have shown that NSAIDs are only 10% to15% more effective than placebo.

  • Second-line treatments. Triptans are the next line of treatment—and they are one of your best options to treat acute migraine attacks.

    The most commonly prescribed is sumatriptan. Research has shown that 65% of patients responded to it within two hours, and 29% were pain free after two hours. (These numbers rise 10% when the drug is injected.)

    Almotriptan, naratriptan, rizatriptan and zolmitriptan have similar efficacy, but Dr. Matchar said that physicians need more research to compare the drugs. Research is especially needed to determine whether physicians can tailor triptan treatment based on patients' needs and specific drug characteristics.

    Although triptans are the primary class of migraine-specific drug on the market, Dr. Matchar said they are far from ideal. "Any individual who has risk factors for coronary artery disease should not take them," he said. A frequent cause of worry for patients is a feeling of pain, pressure, heaviness or tightness in the chest—a common adverse reaction. This condition is temporary, however, and in the vast majority of cases is not coronary-related.

    Evidence shows that another drug, dihydroergotamine (DHE), is as clinically effective as the triptans. While Dr. Matchar said DHE is another secondary option to treat migraines, he pointed out that the drug is most effective when given by injection or intranasally. It is usually given as an injection in the clinic or emergency room, but it is available in intranasal form and some patients can successfully self-inject.

    The College worked with the U.S. Headache Consortium to develop guidelines on treating acute migraines. The guidelines list prochlorperazine, an antiemetic sometimes prescribed for patients whose migraines cause nausea, as a possible second-line treatment. Unfortunately, prochlorperazine frequently causes side affects including sedation, postural hypotension and neuromuscular reactions.

  • Rescue medications. When all else fails, you can always fall back on rescue medications. These agents are often opioids that treat the pain through sedation and analgesia. Because they sedate patients for extended periods of time and have strong side effects, including addiction, they are medications of last resort.

    According to Dr. Matchar, rescue medications can be a positive force, even if they're not used. "When patients know they have something that can rescue them, they may not come into the emergency room and they may not even use the medication," he said.

Stepwise treatment

How should you select the best medication for a specific patient? Dr. Matchar recommended a strategy he called "stepwise treatment," one that evolves over the course of several migraine attacks.

To start, test whether NSAIDs will help by giving patients elevated doses of an NSAID for their first few episodes. Most patients have probably used only over-the-counter versions, which don't provide a high enough dosage.

"If that treatment works, great," Dr. Matchar said. "If it fails, switch them to a triptan and use it right off the bat from then on."

This strategy will help you determine which patients can get relief without using migraine-specific medications that have more side effects.

Because most patients with disabling headaches probably won't respond well to NSAIDs, however, you must tell them exactly what you're doing. "Telling patients you have another plan in mind for them is key," Dr. Matchar explained. "The patient must understand that this is just a trial and that there are other therapies available."

Dr. Matchar advised against using one strategy that is popular among some physicians: During each episode, patients take an NSAID, wait a few hours, take a triptan, then ultimately take a rescue medication.

"For those whose headaches won't respond," he said, "you've just guaranteed two extra hours of pain, nausea and misery." Most specialists say that if medications don't work for a particular patient, there is no use in retrying them for each new attack.

Many specialists use a "stratified therapy" approach, in which they choose a treatment based on the severity of the patient's headache. Patients with mild or moderate headaches start off with NSAIDs, for example, while those with severe headaches go directly to triptans.

"There is some concern that if you delay using migraine specific therapies for a prolonged period," Dr. Matchar said, "patients become less responsive to triptans and more difficult to treat." As a result, patients can develop rebound or drug-induced headaches from NSAIDs.


If a patient experiences migraines several times a month or more, you might consider prophylactic measures, even when drugs are effective.

Eric M. Wall, MD, regional medical director of LifeWise in Portland, Ore., said that while patience is a vice when treating acute migraines, it can be a virtue when seeking to prevent them.

He suggested trying methods over the course of months, not weeks, and keeping in frequent contact with patients on preventive therapies. You need to gauge patient expectations and continually keep them aligned with realistic goals, he explained. "Therapeutic listening and support with this population really does pay off," Dr. Wall said.

Patients have many pharmaceutical options to prevent migraines. Dr. Wall said he drew much of the following information from the U.S. Headache Consortium guidelines on migraine prevention that the College helped develop. (The guidelines are available online at

  • Beta-blockers. While there is good evidence for using beta-blockers, specifically propanolol and timolol, Dr. Wall said that the evidence for other agents is more limited. The mechanism by which beta-blockers prevent migraines is poorly understood. Although they are often well-tolerated, beta-blockers are underused and many physicians don't even consider them. Start at low doses because of side effects, which include nausea, dizziness and depression.

  • Antidepressants. Some tricyclic antidepressants, particularly amitriptyline, have been proven effective. (Evidence on the effectiveness of fluoxetine, however, is more limited.) Because weight gain is a common side effect of amitriptyline, it is less widely used. Dr. Wall tells his patients to take the drug in the evening before going to sleep. Except for dry mouth, most side effects-including anticholinergic symptoms-diminish after the first few weeks.

  • Anticonvulsants. Because anticonvulsants commonly produce side effects such as weight gain, hair loss and tremor, you should prescribe the drugs only when patients experience migraine episodes that are especially prolonged or atypical. Dr. Wall said that few patients can tolerate these side effects. Although the anticonvulsant zonisamide does not cause weight gain and lacks many of the other side effects common to others in the class, there is only anecdotal evidence to support its use.

In terms of efficacy, studies support using valproate and divalproex, though these drugs have been known to cause very serious adverse reactions, including liver failure and life-threatening pancreatitis. Some guidelines recommend gabapentin, which is safer, but evidence supporting its efficacy is limited.

Studies have produced limited evidence showing that NSAIDs other than naproxen offer any prophylactic benefit. In addition, when patients regularly take high doses of NSAIDs, they commonly experience gastrointestinal side effects such as heartburn, nausea and abdominal pain. The high risk of overuse, he added, increases the risk of more serious gastrointestinal problems including ulcers.

In terms of other drugs, Dr. Wall said that studies have found no evidence to support using hormone therapy, calcium channel blockers, magnesium, riboflavin or the herb feverfew to prevent migraines.

Nondrug therapies

Many patients prefer to combine medications with other treatments for migraine prevention. Dr. Wall said that nonpharmacologic treatments are ideal for pregnant or nursing patients for whom acute treatment medications are contraindicated.

Nonpharmacologic options include relaxation training, thermal biofeedback, electromyography biofeedback and stress management. Many physicians are unaware that data support these strategies, Dr. Wall said. Combining them with drug therapies offers even greater benefits.

Little positive evidence supports physical treatments such as acupuncture, transcutaneous electrical nerve stimulation and cervical manipulative therapy, he said, because many of the trials to evaluate them were poorly designed or otherwise flawed.

The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP-ASIM.


Is it really a migraine?

Before you discuss drugs to treat migraines, make sure that your patients' headaches are not secondary symptoms of another affliction.

David B. Matchar, FACP, director and professor of medicine at Duke University Center for Clinical Health Policy Research in Durham, N.C., said that diagnosing migraines is relatively straightforward. If the headaches are episodic and disabling, 80% of the time they are migraines.

You can use the acronym NAIL, which stands for nausea, aggravation by activity, interference with daily life and light sensitivity, as a mnemonic device for classic migraine symptoms.

Dr. Matchar noted that imaging technologies such as CT scans generally do not help diagnose migraines. Data show that only about two out of 1,000 migraine sufferers show any structural brain abnormality, which is less than the incidence in the general population.


A summary of drugs to treat acute migraine headaches

Below is a list of common migraine medications and their primary contraindications and adverse reactions. For complete information on each drug, see the Physician's Desk Reference at

First-line treatments


  • Ibuprofen: Can cause allergic reaction and gastrointestinal irritation. Not to be used by patients with ulcer or kidney disease or during the third trimester of pregnancy.

  • Naproxen: Chronic use can lead to liver and kidney problems, edema and gastrointestinal complications, including bleeding, ulcers and perforations.

Other analgesics

  • Aspirin: Can cause allergic reaction. Not to be used by patients on anticoagulants or women who are nursing or in the last trimester of pregnancy.

  • Aspirin/acetaminophen/caffeine combination: Can cause insomnia. Not to be used by patients who are taking anticoagulants, have an aspirin allergy or are in the third trimester of pregnancy.

Second-line treatments

Triptans: Not to be used by patients with a history of cardiovascular difficulties—especially coronary artery disease and hypertension—nor those with hemiplegic or basilar migraine. Serious cardiac events, although rare, have been associated with triptan use. Tightness of the chest, jaw or neck is common. The nasal spray can cause an unpleasant taste and flushing.

Triptans should not be taken within 24 hours of taking dihydroergotamine because in combination the drugs have a greater chance of causing coronary artery vasospasm. There is little data comparing members of this class.

The oral forms include:

  • almotriptan
  • naratriptan (Takes longer than other triptans to go into effect.)
  • rizatriptan
  • sumatriptan (Subcutaneous form acts more rapidly.)
  • zolmitriptan

Dihydroergotamine (DHE): Not to be used by patients with hemiplegic or basilar migraine. DHE has been linked to serious cardiac events and is contraindicated for women who are pregnant or nursing, as well as patients with impaired liver and kidney function or sepsis. It should not be taken within 24 hours of a triptan because the two drugs combined are more likely to cause coronary artery vasospasm. Side effects include nausea, vomiting, restlessness and flushing.

Rescue medications


  • Butalbital/aspirin/caffeine combination: Side effects include drowsiness, dizziness, sedation, shortness of breath, nausea and vomiting. Can be habit-forming and enhance the effects of other opioids and alcohol.

Opiate analgesics

  • Butorphanol tartrate: Reserve for emergency department use and as a rescue medication. Should not be mixed with alcohol. Can cause constipation, nausea, dry mouth, vomiting, respiratory depression, circulatory depression, heart attack and shock. Overuse can lead to rebound headaches and dependency.

  • Methadone: Reserve for emergency department use and as a rescue medication. Should not be mixed with alcohol. Can cause constipation, nausea, dry mouth, vomiting, respiratory depression, circulatory depression, heart attack and shock. Overuse can lead to rebound headaches and dependency.

  • Acetaminophen with codeine: Do not combine with other central nervous system depressants without reducing the dosage of one of the drugs. Can cause dizziness, sedation, shortness of breath, nausea and vomiting. Should not be given to pregnant women or patients with acetaminophen allergies.


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