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Migraine headaches

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of migraine.

Medications Used for Treatment

Many different medications can treat migraines. Some patients with mild migraines respond well to over-the-counter (OTC) painkillers, particularly if they are taken at the very first sign of an impending attack.

Over-the-Counter (OTC) Migraine Treatments

The FDA has approved three OTC products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relieve of migraine and its associated symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) use a pad containing a gel that cools the skin for up to 4 hours and can be placed on the forehead, temple, or back of the neck.

Ginger. In general, herbal medicines should never be used by children or pregnant or nursing women without medical counsel. One exception may be ginger, which has no side effects and can be eaten in powder or fresh form, as long as quantities are not excessive. Some people have reported less pain and frequency of migraines while taking ginger, and children can take it without danger.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs are among the first types of drugs tried to treat mild-to-moderate migraines. Studies have reported the following benefits for specific NSAIDs:

• Aspirin, ibuprofen, acetaminophen, and naproxen (Anaprox, Aleve) are all available without prescription, and have benefits for mild migraine. Naproxen appears to be more effective than other NSAIDs. In a study of children who had migraines, acetaminophen worked faster, but after 3 hours, ibuprofen was more effective.
• An NSAID combination, diclofenac-potassium (Cataflam), may work faster than the migraine drug sumatriptan (Imitrex) and help reduce nausea. The combination is not appropriate for people allergic to aspirin or at risk for bleeding.
• Injectable NSAIDs, particularly ketorolac (Toradol), are proving to be equally or more effective than the powerful triptan or opioid medications used for severe and persistent migraines. A 2003 study found that intravenous ketorolac provided greater pain relief than nasal sumatriptan (Imitrex). A 2005 study presented at the annual meeting of the American Headache Society reported that intravenous ketorolac was more effective than opioid drugs for late-stage treatment of severe migraine attacks.

NSAID Warning Labels Revised

In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to include with their products a “black box” warning -- the strictest type -- that emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in patient's who use the drugs. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven cardiovascular benefits, aspirin was excluded from these labeling revisions.

COX-2 Inhibitors

COX-2s are a class of prescription drugs that have the anti-inflammatory effects of NSAIDs, but do not upset most people's stomachs. However, some of these drugs have been withdrawn from the U.S. market due to increased risk for heart attack and stroke. Celecoxib (Celebrex) is currently the only available COX-2, and it has a strong warning label alerting users of the potential for heart attack, stroke, and serious gastrointestinal problems. (The warning is the same one the FDA recommended for the labels of prescription NSAIDs in 2005.)

Triptans

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process. Triptans are now recommended as first-line drugs for many adult patients with moderate to severe migraines when NSAIDs are not effective. Patient satisfaction is high with these drugs, and they have the following benefits:

• Effective for most patients with migraine
• Beneficial for patients with combination tension and migraine headaches
• May be effective for preventing menstrual migraines
• Do not have the sedative effect of other migraine drugs
• Withdrawal after overuse appears to be of shorter duration and is less severe than with other migraine medications

Sumatriptan. Sumatriptan (Imitrex) has the longest track record and is the most studied of all triptans. It is available as a fast-dissolving pill, nasal spray, or injection. Injected sumatriptan works the fastest of all the triptans and is the most effective, but it can cause pain at the injection site. The nasal spray form bypasses the stomach and is absorbed more quickly than the oral form. Some patients report relief as soon as 15 minutes after administration. The spray tends to work less well when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Sumatriptan is effective for many patients, but 20 – 40% of people experience a headache recurrence within 24 hours after taking the drug.

Other Triptans. Newer oral triptans include almotriptan (Axert), zolmitriptan (Zomig), naratriptan (Naramig, Amerge), rizatriptan (Maxalt), frovatriptan (Frova), and eletriptan (Relpax). In general, these drugs are similar, but there are some significant differences. Studies on the newer oral drugs have reported pain relief within 2 hours equal to that of injected sumatriptan in 60 - 91% of patients.

Comparison studies with sumatriptan suggest that some of the newer drugs have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. They are also being investigated for prevention under certain circumstances, such as menstrual migraines, but benefits appear limited.

Some observations:

• Almotriptan is as effective as oral sumatriptan and may have fewer side effects, particularly chest pain, than most other triptans. It may prove to be one of the most cost effective of these drugs.
• Rizatriptan may have the most rapid effects of all oral triptans. Zolmitriptan also has a more rapid effect than sumatriptan (although there appears to be no significant difference in adverse effects). Both rizatriptan and zolmitriptan are also available as rapidly dissolving wafers.
• Eleptriptan is also very rapidly effective at high doses, but at those levels may have significant adverse effects. (To date, it does not seem to have any advantages over other triptans in head-to-head comparisons.)
• Naratriptan and frovatriptan have a delayed response but long duration, few side effects, and lower risk for recurrence than with sumatriptan. Some evidence suggests that they may have specific benefits for stopping prolonged migraines and may even play a role in prevention.
• Frovatriptan: A large study of more than 500 women with an average 12-year history of menstrual migraines examined the use of frovatriptan for the short-term prevention of such headaches. Researchers found that the migraines disappeared in over half of the women on the higher dose (5 mg) of frovatriptan.
• Zolmitriptan (Zomig): A study presented at the 2005 annual meeting of the American Headache Society suggested that zolmitriptan nasal spray may be safe and effective for adolescents. Zolmitriptan relieved pain within 2 hours for nearly half of the children (aged 12-17 years) enrolled in the trial. Zolmitriptan nasal spray is currently approved only for adults.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include:

• Tingling and numbness in the toes
• Sensations of warmth
• Discomfort in the ear, nose, and throat
• Nausea
• Drowsiness
• Dizziness
• Muscle weakness
• Heaviness, pain or both in the chest. (About 40% of patients taking sumatriptan experience these symptoms and they are major factors in discontinuing the drug. Newer drugs, such as almotriptan, produce fewer chest symptoms.)
• Rapid heart rate

Complications of Triptans. The following are potentially serious problems.

• Complications of Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this effect, spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
• Serotonin Syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptan drugs used to treat migraine, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) -- such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with a SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following groups should avoid triptans or take them with caution and only with the advisement of a doctor:

• Anyone with a history or with any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
• People taking antidepressants that increase serotonin levels.
• Children and adolescents. They may be safe, but controlled studies are needed to confirm this. (Triptans should not, in any case, be the first-line treatment for children.)
• People with basilar or hemiplegic migraines. (Triptans are not indicated for these migraineurs.)
• There is no evidence to date of any higher risk for birth defects in pregnant women who take triptans. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their doctors.

Ergotamine (Ergot)

Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first specific anti-migraine drugs available. Ergotamine is available in the following preparations:

• Dihydroergotamine (DHE) is an ergot derivative. It is administered as a nasal spray form (Migranal) or by injection, which can be performed at home.
• Ergotamine itself is available in oral tablets (Ergomar, Wigraine, Ercaf) and in rectal suppositories (Cafergot). Cafergot, Wigraine, and Ercaf contain caffeine.

Their role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Injected, oral, and nasal-spray forms are all inferior to the triptans. Ergotamine may still be helpful for patients with status migrainous or those with frequent recurring headaches.

Side Effects. Side effects of ergotamine include:

• Nausea
• Dizziness
• Tingling sensations
• Muscle cramps
• Chest or abdominal pain

The following are potentially serious problems:

• Toxicity. Ergotamine is toxic at high levels.
• Adverse effects on blood vessels. Ergot can cause persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke.

Internal scarring (fibrosis). Scarring can occur in the areas around the lungs, heart, or kidneys. It is often reversible if the drug is stopped.

The following patients should avoid ergots:

• Pregnant women. Ergots can cause miscarriage.
• People over age 60.
• Patients with serious, chronic health problems, particularly those of the heart and circulation.

Lidocaine

Nasal drops containing lidocaine, a local anesthetic, can provide effective pain relief within 15 minutes for many migraine sufferers. However, lidocaine has certain downsides:

• It is rather difficult to administer. Patients must be lying down with their head dangling.
• The headache often relapses in an hour, and other drugs must then be used.
• Side effects include unpleasant taste, burning sensation, and facial numbness.

However, the drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. Its fast effectiveness and safety make it a promising first drug during a migraine attack. It should not be used for any other form of headache.

Opioids

If the pain is very severe and does respond to other drugs, doctors may try painkillers containing opioids [morphine, codeine, meperidine (Demerol), or oxycodone (Oxycontin)]. Butorphanol is an opioid in nasal spray form that may be useful as a rescue treatment when others fail. Several such drugs use combinations of opioids plus NSAIDs (ibuprofen or aspirin) or acetaminophen. One study reported that about half of patients who start opioid therapy for migraine respond well and the benefits persist over time. In a major 2002 analysis of over 800,000 headache cases, Demerol was the most commonly administered drug (30% of migraine cases). Nevertheless, experts do not recommend opioids as first-line therapy for migraine sufferers.

Side Effects. Side effects for all opioids include drowsiness, impaired judgment, nausea, and constipation. There is a risk for addiction, and they can become ineffective with long-term use for chronic migraines. Such drugs should not be prescribed for patients at risk for drug abuse, including those with personality or psychiatric disorders.

Drugs Used for Nausea and Vomiting

Metoclopramide (Reglan) is used in combinations with other drugs to treat the nausea and vomiting that occurs with other drugs and with the condition itself. Metoclopramide and other anti-nausea drugs, such as domperidone (Motilium), may help the intestine absorb migraine medications.

• Review Date: 10/2/2006
• Reviewed By: Harvey Simon, M.D., Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

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