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New Drugs Help Tame Migraines
Washington Post Staff Writer Tues., March 31, 1998; Page Z10 About 10 times a month, Cara Acosta feels one coming on. Usually it starts with an "aura," an hour or so before the hammering pain. Suddenly everything seems jagged-edged and too intense: lighting, sounds, talk, motion, pictures on the wall, traffic on the street. "Like sitting too close to a movie screen," she says. Straight lines go zigzag, overhead lights fire like flashbulbs. She becomes disconcertingly aware of her own swallowing and pulse. Her left arm gets tingly, her shoulder stiffens and she feels the headache "creeping up behind my eye."
Later, if quiet and a little white 50-milligram pill doesn't do the trick, the pain strikes. At its worst, she says, it feels "as if someone drove an icepick through that eye and spends the rest of the day pulling it out and punching it back in." But these days, Acosta counts herself lucky. Nine times out of 10, the migraine doesn't reach that point. She can usually abort the impending pain with a single dose of sumatriptan (sold as Imitrex). Four years ago, she was gobbling a haphazard mix of aspirin and other pain relievers -- and still unable to fend off a nearly continuous headache.
"It used to be doctors just blew them off," says Thomas Ward, a neurologist and headache specialist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. "Now patients won't put up with that." As recently as a few years ago, Ward says, "you took a couple of Cafergot [an early anti-migraine drug] and lay down and toughed it out. Now there's a whole parade of new drugs." In the past few months alone, half a dozen new medications for migraine have been approved by the Food and Drug Administration, and more are in the testing and regulatory pipeline. "Just because their mothers had crippling headaches 30 years ago doesn't mean there's nothing new for them," says John H. Lossing, a neurologist and director of the headache center at Georgetown University Medical Center. Like most migraine patients, Acosta dropped out of medical treatment during the 1970s and 1980s. "Either there wasn't anything for them, or they didn't pursue it long enough to find the right combination," Lossing says. Studies have shown that most people with migraines never see a doctor, partly because they don't believe migraine the condition is treatable. That view is sorely out-of-date, experts say. Migraine therapy has come a long way from antiquity's last-resort treatments, which ranged from bloodletting to applying a hot iron to the head or drilling a hole in the skull to release evil spirits. More importantly for patients like Acosta, it has come a long way from just five years ago. "The way migraine has been addressed has drastically changed," says Michael John Coleman, executive director of Magnum, a migraine awareness group in Alexandria.
Freud, Van Gogh and Elvis An estimated 24 million Americans get migraine headaches at some point in their lives. Three out of four are women. Some 3.4 million women and 1.1 million men suffer at least one migraine attack per month. Migraines can strike at any age, but they often start in the teenage years, peak between 35 and 45, and abate after 50. In a 1994 Gallup poll of migraine sufferers, one out of three said the pain sometimes made them wish they were dead. For them it's little consolation that such famous figures as Julius Caesar, Thomas Jefferson, Sigmund Freud, Charles Dickens, George Eliot, Virginia Woolf, Vincent Van Gogh and Elvis Presley are said to have shared their affliction. Or that certain scenes of "Alice's Adventures in Wonderland" may have come to Lewis Carroll during his migraine auras, and Ulysses S. Grant's fierce migraine resolved spontaneously when word came of Robert E. Lee's readiness to surrender. Although they overlap with other types of headache, migraines have distinctive features. Most obvious is the throbbing, sometimes incapacitating pain, usually (but not always) on one side of the head. The word itself comes from the Greek for "half" and "skull." Unlike more common "tension" headaches, migraines typically entail acute sensitivity to light and sound, and may cause nausea and vomiting. "The pendulum is now swinging back toward defining migraine as separate from so-called tension headaches," says Kenneth L. Moore, a neurologist and former director of the Head Pain Center at the University of Mississippi Medical Center in Jackson. Moore himself was first hospitalized for migraines in 1972, when he was a first-year medical student at the University of Chicago. He had been knocked unconscious during a softball game. At that time, the diagnosis of migraine carried a psychological stigma. Migraine sufferers were widely thought to fit a "migraine personality" -- overly self-critical, rigid, perfectionist and obsessively organized. "Having seen 7,000 patients since 1978, I can tell you that being a slob will not cure your migraine headaches," Moore says. Although migraine sufferers as a group may be more subject to depression and panic attacks than others, "migraine personality" is a misleading term, he says. "One size does not fit all." As neurologist Oliver Sacks noted in his book, "Migraine," people who get migraine headaches are "as remarkable for their diversity as any other section of the population." Old Affliction, New Drugs Exactly how a migraine headache develops remains something of a mystery. Doctors know it involves a narrowing and then a widening of blood vessels in the brain. Inflammation of blood vessels deep within the brain can jangle nerve endings linked to brain centers that control vision, pain and nausea. Intricate computerized brain images called PET scans show changes in blood flow during a migraine headache. Typically, a decrease in blood flow begins in the back of the brain and spreads forward. Later, when the constricted blood vessels widen, or dilate, the rush of blood causes intense pain. What causes the blood vessels to narrow and widen is not fully understood, but it's clear that a key role is played by a versatile and wide-ranging brain chemical called serotonin. Among its many hormonal effects, serotonin causes blood vessels to constrict. During a migraine attack, the level of serotonin in the brain appears to drop, allowing blood vessels to dilate. The added blood flow inflames and swells surrounding tissues, including nerve endings that transmit pain signals within the brain. Many of the new anti-migraine drugs work by mimicking or activating serotonin in the brain. The challenge in designing such drugs is to make them selective -- so that they activate serotonin's helpful effects, while blocking its harmful effects, such as nausea. The drug Acosta takes, sumatriptan (Imitrex), is the first selective serotonin-activator, as well as the first major anti-migraine drug in more than 30 years. It came onto the market in 1993 and is now available in three forms: injection, nasal spray and tablets. Other drugs from the same class, called triptans, have followed rapidly, including zolmitriptan (Zomig) last November and naratriptan (Amerge) last month. Rizatriptan (Maxalt) was recently approved for marketing in Mexico and Europe and is under review by the FDA. A nasal spray version of an older drug, DHE-45, was approved in December and is now sold as Migranal. Excedrin Migraine went on the market this year, though only the packaging is new: The tablets are identical to the combination of aspirin, acetaminophen and caffeine already sold as Extra-Strength Excedrin. The first specifically anti-migraine drug, ergotamine or ergot, became available in the 1930s. Mixed with caffeine, it was sold under the brand name Cafergot. A related drug called dihydroergotamine, or DHE, followed. From the 1950s until the recent advent of Imitrex, they became the mainstays of treatment, along with tranquilizers and nonspecific pain relievers. Now Imitrex and its chemical cousins are revolutionizing migraine treatment, doctors and patients say. Yet even with more therapies than ever available, finding the most effective treatment for migraines can be a frustrating trial-and-error process, as much art as science. In patients who suddenly start getting severe headaches, doctors may order a brain scan to rule out a specific underlying cause such as a tumor or an aneurysm. They ask about family history, because migraines tend to run in families. Patients also may be asked to keep a "migraine calendar" to track their headache patterns and pinpoint possible migraine "triggers" -- such as stress, weather shifts, hormonal changes including menstruation, lack of sleep, alcoholic drinks (especially red wine) and food such as nuts, chocolate or cheese. Such triggers are notoriously variable. For example, caffeinated beverages can help ward off a headache, but overdoses of caffeine can also bring on a headache. The worst headache Lossing ever had came several years ago after he switched coffee brands to take advantage of a supermarket sale. He boosted the dose to make up for the new brand's lack of taste, effectively doubling his caffeine intake to the equivalent of nine cups in one day -- and triggering a migraine. Biofeedback -- in which a machine records and "feeds back" data on muscle tension, pulse and skin temperature -- may help some patients learn to relax or "train" their blood vessels to dilate. If nonmedical efforts -- reducing stress, avoiding dietary triggers, getting enough sleep -- don't control the migraines, doctors consider medication. The drugs fall into three broad categories: analgesics to relieve pain, abortives to cut short an impending migraine and preventives to reduce the number of headaches. Headaches that aren't too severe or frequent may respond to over-the-counter pain relievers such as aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin, Nuprin) or naproxen (Naprosyn, Aleve). For migraines that strike once or twice a month, doctors often prescribe a stronger migraine-aborting drug such as ergot, isometheptene (Midrin) or one of the new triptans. Triptans such as Imitrex don't work for everyone, and sometimes cause troublesome side effects. And because they constrict the blood vessels, triptans pose a risk for patients with heart disease or uncontrolled blood pressure. Nor do the new anti-migraine drugs come cheap -- each Imitrex tablet costs around $15 and an injection runs about three times that. But Dartmouth's Ward notes that they are a bargain if they prevent a far more costly visit to a doctor or a hospital emergency room. Headaches account for about 5 percent of emergency room visits, and a 1994 study showed that the average emergency room visit for headache cost $569. If migraines occur more than twice a month, doctors may prescribe preventive medications. Depending on the patient, those may include antidepressants or cardiovascular drugs such as beta blockers or calcium channel blockers that may help prevent migraines by keeping blood vessels from swelling. A commonly prescribed beta blocker is propranolol (Inderal). "Rule No. 1," Ward says, "is that treatment shouldn't be worse than the problem." That means avoiding narcotics because of their potential for addiction and balancing the side effects of other drugs. Migraine's Vicious Cycles Acosta's migraines first struck 20 years ago when she was 17. She thought it was the stress of starting college. Only later did she realize migraines ran in her family. "My mother would get very sick and would close the door," she recalls, "and we'd have to leave her alone." Acosta was put on tranquilizers and sedatives. They softened the worst spikes of pain but left her with a sluggish feeling and a kind of chronic low-grade headache, which she tried to control with over-the-counter analgesics such as aspirin. During her twenties, the headaches grew more severe and more frequent. Often she had to retreat to the floor of her closet -- "the quietest, darkest place I could find." Once, the pain got so unbearable that she asked her boyfriend to knock her out "if he could promise me he'd do it in one punch." (He refrained.) With time, the headaches abated, and she kept them under control with aspirin and Midol. But a few years ago they flared up again. By then she was working as a secretary in a Washington law firm, and consuming nonprescription painkillers willy-nilly. She remembers days when she took 15 pills, mixing Excedrin, Tylenol, Advil and aspirin -- "whatever was around" -- in a desperate effort to quell the pain. Some weeks, she went through an entire bottle of 50 aspirin tablets. "They didn't help, really," she recalls. "But I had to take something. When you're in that kind of pain you don't have the calm to choose carefully." Migraines have many ways of becoming a vicious cycle. The pain interrupts sleep; lack of sleep can prolong or trigger a headache. Relaxation can ease a migraine, but how do you relax when you're in pain? Fear of pain drives patients to take too much ineffective medication, which can actually make the problem worse -- a phenomenon known as analgesic rebound. "Pretty soon you're taking more medicine and getting more headaches, and nothing works," neurologist Ward says. "Probably several million patients are wandering around with chronic headaches caused by analgesic rebound." One patient came to him after suffering almost continuous daily headaches for two years. She was taking Extra Strength Tylenol around the clock -- 780 tablets a month, or 26 a day (three times the maximum recommended dose). When Ward took her off the pain reliever, her headaches stopped. A similar change happened to Acosta after she finally decided to see a doctor about her worsening headaches and wound up in Lossing's office. "Some patients have a headache every day for years, and if we stop the analgesic they go back to one a month," he says. Today, Acosta controls her migraines with two prescription drugs: twice-daily tablets of verapamil (Calan), a drug normally taken for high blood pressure, and Imitrex as needed, whenever she feels a bad migraine coming on. The triggers on what she calls her "no-no list" include stress at work, lack of sleep, foods such as nuts, cheese and chocolate, and red wine. She is more prone to migraines during her menstrual period. Nine migraines out of 10, she can ward off the worst with a timely Imitrex and calm-down quiet. Once a month, the migraine won't quit and she has to sleep it off. Rarely, it drags on for two or three days. "Even after 20 years, there are times when I'm still grasping at straws," she says. A week ago last Friday, she went to bed with a bag of frozen peas against her head in an effort to abort a one-in-10 migraine that Imitrex didn't help. Over the years, she has tried nearly every form of mainstream and alternative treatment, including acupuncture, chiropractic and the herb feverfew, a yellow chrysanthemum first touted in the 17th century as a headache remedy. "When you're trying to get rid of pain, you'll look into anything," she says. Because headache pain is less visible than, say, a broken ankle or a black eye, migraine patients "get very little sympathy," Lossing says. They get migraines at inconvenient times -- graduations, proms, weddings and the first day of vacation. Fear can govern their lives. Acosta hates to travel, for one simple reason: "Any breaking of routine usually keeps me with a headache for the first two days." But at least now she has medicines that help. When Georgetown's Lossing starting treating migraine patients in the mid-1970s, there was little to offer them besides tranquilizers and nonspecific painkillers. He could hardly blame patients who gave up on medical treatment for their migraine attacks. "Today we have a lot more -- and better -- medicines available," Lossing said. "It's a whole new approach."
Resources American Council for Headache Education (ACHE), 800-255-2243. National Headache Foundation, 800-843-2256. Migraine Awareness Group: A National Understanding for Migraineurs (MAGNUM), Alexandria, 703-739-9384. Headache Center, Georgetown University Medical Center, 202-687-8821.
© Copyright 1998 The Washington Post Company |
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