Migraine Headaches

Description

Medications

Over-the-Counter (OTC) Migraine Treatments. Some patients with mild migraines respond well to OTC painkillers, particularly if they are administered at the very first warning of an impending attack. The Food and Drug Administration (FDA) has approved three over-the-counter products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first OTC 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.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs are also first-line drugs tried for mild to moderate migraines. They are not very effective when used alone against severe migraine headaches. Some experts suggest that the effect that the migraine process has on the gastrointestinal (GI) tract may prevent the absorption of NSAIDs. Some studies reporting benefits for specific NSAIDs include the following:

• Aspirin, ibuprofen (Advil Migraine), and naproxen (Anaprox, Aleve) are all available over the counter, and may have some benefits for mild migraine. Naproxen appears to be more effective than other NSAIDs. A study of children who had migraines compared ibuprofen and acetaminophen. Acetaminophen worked faster, but after three hours, ibuprofen was more effective. Parents of children with migraines should consult with their physicians about using a combination of these drugs.
• Researchers have combined a high-dose NSAID (equivalent to 900 mg of aspirin) with metoclopramide (Reglan), a drug that prevents nausea and vomiting. Several studies show this combination is equal to oral sumatriptan and superior to DHE, two standard migraine drugs. People should not take high doses of NSAIDs without some protective agent since they can cause severe gastrointestinal distress.
• In one study, an NSAID combination, diclofenac-potassium (Cataflam), was as effective as sumatriptan, a standard migraine drug. Cataflam worked more rapidly and helped 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 that powerful migraine medications used for severe and persistent migraines. A 2003 prospective, double-blind study found that intravenous ketorolac produced a greater reduction in pain than did nasal sumatriptan (Imitrex). It should be noted that ketorolac has a higher risk for gastrointestinal bleeding than many other NSAIDs.
• Rofecoxib (Vioxx), a newer NSAID called a selective COX-2 inhibitor, was FDA approved in April 2004 for acute migraines. Studies show that a 50mg daily dose of rofecoxib relieved pain for most within 2 hours. Additional studies looking at preventing migraines in perimenstrual women found that rofecoxib at a daily dose of 25 or 50 mg resulted in "a significant reduction in frequency of perimenstrual migraine." Researchers emphasize that further study of rofecoxib in the prevention of perimenstrual migraine is warranted.

Other selective COX-2 inhibitors include celecoxib (Celebrex) and meloxicam (Mobic). These agents may allow high doses without the accompanying gastrointestinal side effects.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) employ a pad containing a gel that cools the skin for up to four 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.

Triptans

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine and are the most important migraine agents 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 agents for many adult patients with moderate to severe migraines when NSAIDs are not effective. Patient satisfaction is high with these agents and they have the following benefits:

• They are effective for most migraine patients.
• They are beneficial for patients with combination tension and migraine headaches.
• They may be effective for preventing menstrual migraines.
• They 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 can be administered orally in table form, as an injection, or as nasal spray. Injected sumatriptan works the fastest of all the triptans and is the most effective. It is inconvenient, however, and has the most adverse effects, including 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 be less effective when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Nevertheless the spray form is effective and tolerable even for children and young people. In February 2004, a reformulated version of sumatriptan tablets was released. The new fast dissolve tablets replace the older ones. In an in vitro study, the new tablets, which are swallowed just like conventional tablets, dissolved five times faster than conventional tablets, which may allow the drug to be absorbed into the blood stream quickly. Unfortunately, recurring headaches develop within the first 24 hours in 20% to 40% of people who have taken 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 agents are similar but there are some significant differences. Studies on the newer oral agents have reported pain relief within two hours equal that of injected sumatriptan in between 60% and 91% of patients.

Comparison studies with sumatriptan are suggesting that some of the newer agents 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 are 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 agents.
• 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. Study patients received either a placebo, or a 2.5mg or 5mg dose of frovatriptan six days a month, starting two days before their period. Researchers found that the migraines disappeared in over half of the women on the higher dose of frovatriptan.

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

• 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 agents, such as almotriptan, produce fewer chest symptoms.)
• Rapid heart rate.

Complications of Triptans. The following are potentially serious problems.

• Complications on the Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this effect, very rarely spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are only rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
• Serotonin Syndrome. Triptans also affect serotonin and so people taking antidepressants that increase serotonin levels (which are most antidepressants) should avoid taking both. The effects of such combinations may cause a so-called serotonin syndrome, which causes mental changes, restlessness, tremor, chills, sweating, and colitis. Some physicians believe, however, that the risk for the syndrome from taking both classes of drugs is very small.

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

• 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.)

Of note: There is no evidence to date of any higher risk for birth defects in pregnant women who take them. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their physicians.

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 agents 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 the following:

• 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.
• People over 60.
• Those 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. One case report suggests that taking it during the aura phase may offer significant protection against developing the full-blown headache. It 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. And 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 agents, physicians may try painkillers containing opioids (e.g., 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. A number of such agents 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.

Agents Used to Prevent Nausea and Vomiting

Metoclopramide (Reglan) is used in combinations with other agents to treat the nausea and vomiting that occurs with other drugs and with the condition itself. In fact, in one study using only aspirin with metoclopramide had some significant effect on the migraine itself. This and other anti-nausea drugs, such as domperidone (Motilium) may also help the intestine absorb the migraine medications.

Investigative Treatments

Intravenous Magnesium. Intravenous magnesium sulfate has been useful for migraine relief in some people, but which patients will benefit is unclear. In one study, this treatment helped only migraine sufferers with magnesium deficiencies. Some studies have reported magnesium deficiencies in women with menstrual migraines. It would follow, then, that intravenous magnesium might help this group. However, in a 2002 study, magnesium significantly reduced all symptoms in patients with auras, but had no effect on pain relief for migraine patients without auras. Given this evidence and because true menstrual migraines occur without auras, the effects of magnesium on these patients is unclear.

Intra-Oral Chilling. An interesting investigative approach is based on the idea that many headaches are associated with inflammation in the areas above the upper molar teeth. This creates swelling and puts pressure on the maxillary nerves, which are behind the cheekbones. Investigators are studying the use of hollow tubes containing circulating ice water, which the patient holds against areas in the mouth thought to be inflamed. A small 2001 study reported that the device was as effective as sumatriptan in relieving headache pain. In addition, it appeared to relieve nausea.