Prevention: The Future of Migraine Therapy

Stopping a migraine headache before it ever begins is the new focus of treatments.

From the WebMD Archives

Taking a shower hurts. Shaving hurts. Even your hair hurts when you're in the throes of a migraine headache.

Until a few decades ago, people had little more than aspirin to fight the throbbing, debilitating pain of a migraine headache. Then, in the 1980s, researchers developed strong drugs to halt migraine pain once it begins. But those drugs have serious side effects. Some people cannot take them if they are at risk for heart disease or other conditions. Also, if the drugs are not taken within the first hour of migraine headache pain, they don't help much.

These older drugs are still prescribed. But more recently, the approach to taming this lion has made a 360-degree turn. Now, prevention is the focus. It involves disabling a migraine headachebefore the pain ever begins. One method is to take non-migraine drugs daily to help prevent a migraine from starting. The drugs affect brain chemicals or blood vessel inflammation that lead to migraines.

Another is to fine-tune treatment for each patient. The goal is to take fewer drugs, avoid many side effects, and have better control of the beast. For example, you become aware of your pattern of getting a migraine headache, learn what triggers it, and take certain drugs during your own window of vulnerability - that is, the brief window of time you can most benefit from a drug.

Finding Your Migraine's Window of Vulnerability

The FDA is currently reviewing a new migraine drug called Trexima, which combines the migraine drug Imitrex (sumitriptan) and naproxen sodium (a nonsteroidal anti-inflammatory drug) contained in Aleve and other over-the-counter medications. The triptan prevents blood vessels from dilating. This dilating leads to migraine pain; the anti-inflammatory drug prevents release of an inflammation-triggering enzyme, according to product developers.

Also in the pipeline: A drug that shows promise as both in preventing migraines and in stopping a migraine once one starts, says George R. Nissan, DO, director of research for the Diamond Headache Clinic in Chicago. The drug works by inhibiting a protein released during inflammation, called calcitonin gene-related peptide (CGRP). CGRP is found in high levels in migraine patients.

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"We're looking for migraine drugs that don't have the limitations or side effects of antiseizure or blood-pressure-lowering drugs," Nissan tells WebMD. "CGRP doesn't cause constriction of blood vessels, so there would be fewer worries for patients with heart disease, and fewer limitations on its use. However, it may take years until we see it FDA-approved."

Stephen Silberstein, MD, professor of neurology and director of the Thomas Jefferson University Headache Center in Philadelphia, has led pioneering studies into this "window of vulnerability" during a migraine headache.

For certain people, especially women with menstruation-related migraines and others whose triggers are well-defined and predictable, this pre-emptive approach is indeed the future, he tells WebMD. "More studies are looking at taking preventive drugs during that brief window. For patients, it's a matter of getting tuned into your particular pattern."

For those who can't take medications or aren't happy with them, a few supplements also show promise for preventing migraine headaches. "In my own practice, I recommend these if there are at least two well-controlled clinical trials showing benefit," says Sarah DeRossett, MD, a neurologist and migraine specialist in Atlanta. "Magnesium, riboflavin (vitamin B-2), and coenzyme Q10 all fit those criteria."

Migraine Headaches Connected to Hormones, Lifestyle

To understand how all this works, it's helpful to know how migraine headaches develop. The tendency to get them is inherited. They plague teen girls and adult women especially, although a small number of young boys and adult men get migraines as well, researchers say.

Female hormones such as estrogen influence migraines, though it's not clear why. The drop in estrogen levels that occurs a few days before a normal menstrual period seems to increase the chances of a migraine, possibly by priming blood vessels in the brain.

If a woman is taking birth control pills, her headaches are most likely to occur during her "off week," when estrogen levels drops. Some women start getting migraines only at menopause, when their period stops. For others, menopause is the first real relief from migraines.

Lifestyle and environment can also trigger migraines. Weather changes, altitude changes, bright lights, sleep problems, stress, smells, cheeses, caffeine, monosodium glutamate (MSG), nitrates, or aspartame are just some of a long list of potential triggers. Every migraine patient has his or her own headache trigger pattern.

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The evolution of a migraine starts with this trigger: When your brain perceives the trigger, it begins a cascade of events. The headache will start developing within two hours or two days. In the beginning, blood vessels in your forehead start to swell up. This causes nerve fibers, which are coiled around the blood vessels, to release chemicals causing pain and inflammation.

A vicious cycle develops: The inflammation makes the blood vessels enlarge even more, making the pain only worse. When this chain-reaction process goes on for an hour or two, it achieves a new threshold.

"It's called 'central sensitization,' and it tends to perpetuate the headache," explains Seymour Solomon, MD, director of the Montefiore Headache Unit at Albert Einstein College of Medicine in the Bronx, N.Y. At that point, the chain-reaction of pain begins traveling along nerve pathways throughout the head, to the base of the neck and to the spine.

That's when everything starts hurting, Solomon tells WebMD. The pain-nerve cells are stuck in the "on" position. The slightest touch or movement hurts. Even the pulse of blood in your brain causes pain. Your intestinal system gets thrown out of whack, too, by the onset of nerve chemicals. You feel nauseous, you throw up, you get diarrhea. Your hands and feet grow cold. The color drains from your face.

There's nothing pretty about having a migraine.

Not everyone has this threshold or central sensitization effect, researchers say. Luckily, these patients can take existing painkillers such as Motrin, Advil, Excedrin, or certain prescription pain drugs. These are nearly 100% effective in kicking their headaches, says Solomon.

But most people with migraines need more effective drugs. They must take them before the headache lasts an hour. After that, some relief will come, but usually not enough.

Too many people ignore those very early symptoms, Solomon tells WebMD. "These people get lots of headaches, which are often tension headaches, and they hope against hope that this one isn't a migraine. So by the time the window is past, it's too late to stop it."

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In the early days of migraine research, a class of drugs called ergots (short for ergotamines, such as dihydroergotamine or DHE) was aimed at stopping migraine pain in progress. Then came the triptan drugs, which were even more effective at halting pain. They include:

Both ergot and triptan drugs are still prescribed today, Solomon says. However, because both drugs work to constrict swollen blood vessels, not all patients can take them. "If a patient has heart disease or high blood pressure, they just can't take those drugs," he tells WebMD.

Preventing Migraines in the First Place

More recently, to try to stop migraine headaches from developing at all, doctors have prescribed drugs used to treat other disorders. These drugs are taken daily to suppress the brain chemical or blood vessel activity that leads to migraines. The hope is to prevent a migraine from getting started. These drugs include:

"All these are able to keep migraines from happening," says Silberstein. The problem with most, however, is side effects. Topamax can cause numbness, tingling, heat sensations, slowed thinking, and weight loss. Some calcium channel blockers, tricyclic antidepressants, and Depakote can cause weight gain.

"The bottom line is, you pick side effects," says Silberstein. "I tell the patient, 'This drug may have cognitive side effects in some people, may make you lose weight, or here's one that may make you gain weight. Which one do you choose?' With Topamax, you know right away if you'll have side effects. With the others, the side effects [such as weight gain] sneak up on you."

Despite all these advances, some patients still suffer. "One in 10 migraine patients cannot tolerate certain migraine medications. So we're better than we were, but we're still not perfect," Silberstein notes.

For some desperate people, the muscle-paralyzing drug Botox, usually given via injection to facial muscles to reduce the appearance of wrinkles, is a saving grace, he says. "Botox seems to work for patients who get frequent migraines, more than those with infrequent ones. If it works, the treatment is every three or four months." However, Botox treatments can be expensive. "Sometimes insurance covers it, but often it doesn't," he notes.

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Finding the Window of Vulnerability

In another approach to the goal of preventing migraine headaches, Silberstein and other researchers have looked at "drug timing." This involves finding the window of vulnerability, a critical time period for migraine headache sufferers. If patients can take their drugs just at this point instead of ongoing, some side effects can be offset. They'll also take less medication, cutting out-of-pocket costs.

Two recent studies of menstrual-related migraines produced the first scientific evidence for a pattern of vulnerability in migraine headaches. Researchers say their findings could apply to other types of migraines, not just menstrual headaches.

It's an exciting finding. If altitude changes are your nemesis, then taking a long-acting triptan drug twice a day on the day before you go skiing in Utah and continuing it for a week may nip your migraine from starting at all.

New migraine drugs are also on the horizon. "A lot of drugs are coming down the pipeline, drugs that work by different mechanisms," says Silberstein. One is a class of enzyme-blocker drugs, such as Aricept, currently prescribed to treat mild to moderate confusion related to Alzheimer's. This drug is a contender for migraine prevention, he tells WebMD.

Alternative Choices for Migraine Pain

While medications are the mainstay of migraine treatment, they're not a cure-all. For women who are pregnant or hoping to be, supplements are a safe alternative. For people who can't get enough relief from prescriptions or who dislike the side effects, supplements can also help.

"Almost anyone, including children, can take magnesium," DeRossett tells WebMD. "The only side effect is diarrhea. Some people get it, some don't. For some, it's dependent on how high the dosage is."

She recommends magnesium "more than other supplements, and have found it to have the most robust effect in preventing migraines," she says. "I advise vitamin B-2 if a patient has a predisposition to diarrhea." Some supplements combine magnesium, vitamin B-2, and the herb feverfew. Coenzyme Q10, which the body produces naturally, has also been shown to cut migraine attacks, but it's pricier than the others, she adds.

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You have to take magnesium for three months to get a benefit, says DeRossett. "People sometimes give up on it too soon." Taking the correct dosage is important as well: 500 mg magnesium, 400 mg riboflavin (vitamin B-2), and 150 mg coenzyme Q10.

The herb butterbur can also help prevent migraine attacks, she adds. A recent study found that a daily 75 mg butterbur supplement cut migraine frequency by more than 50%.

"Our patients are on all kinds of high-powered migraine headache medications," DeRossett tells WebMD. "These [magnesium, etc.] aren't in the same ballpark as Depakote or Topamax. But for some people, magnesium might be enough. For others, it might provide added benefit in terms of relief."

WebMD Feature

Sources

SOURCES: George R. Nissan, DO, director of research, Diamond Headache Clinic, Chicago. Stephen Silberstein, MD, professor of neurology; director, Thomas Jefferson University Headache Center, Philadelphia. Seymour Solomon, MD, director, Montefiore Headache Unit, Albert Einstein College of Medicine, New York. Sarah DeRossett, MD, neurologist and migraine specialist, Atlanta. American Council for Headache Education. WebMD Medical News: "Super-Sensitive Nerves Play Key Role in Migraine Pain." WebMD Medical News: "Taking the Pain Out of Migraine Treatment." WebMD Medical News: "Epilepsy May Reduce Daily Headaches." WebMD Medical News: "Hope for Preventing Menstrual Migraine." WebMD Medical News: "Menstrual Migraines May Be Preventable." WebMD Medical News: "The Many Faces of Botox:" News release, GlaxoSmithKline. Product Candidate Report, Pozen.

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