Why Did It Take So Long to Figure Out Migraines?

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To be clear: A migraine is not a headache, and people with migraines don’t like their condition being called one. It’s not that headaches aren’t part of a migraine: They are. But a headache is a single symptom of a multifaceted neurological disease — one that includes loss of vision, intense nausea, and sensitivity to light and sound. And those are just the common side effects. Some sufferers find themselves yawning compulsively, slurring their speech, and losing sensation on one side of the body. Some migraineurs (yes, that is the technically accurate moniker for migraine sufferers) start seeing big things as small — a side effect dubbed “Alice in Wonderland syndrome” by doctors.

Nonetheless, for as long as they have existed, migraines have been trivialized as headaches or dismissed altogether. Which is clear when you look at the treatments available: Almost every drug used between 1550 B.C. and today has been a repurposed one. Poultices of opium and honey, botox, anti-convulsant drugs, antidepressants, beta blockers — drugs whose efficacy was not intended but stumbled upon. Triptan, a class of vessel constrictors created to abort and lessen the effects of (not prevent) attacks at their onset was released in 1991. It was the only class of drug created specifically for migraines — that is, until now. On May 17, a preventative drug called Aimovig, 30 years in the making, gained FDA approval; it’s a monthly shot that modulates patients’ levels of CGRP, a neurotransmitter whose levels rise during migraine attacks. This means that it is days away from getting in the hands (or arms — it’s an injectable) of migraineurs. At at least for those who are able to pay full price: The drug costs $6,900 a year, or $575 per treatment.

That it took until 2018 to produce a drug that could help up to 39 million people in the U.S. alone — 18 percent of all American women, 6 percent of men, and 10 percent of children — is mostly due to a long-standing misunderstanding of what happens in a person’s body during a migraine attack, says neurologist Dr. Peter Goadsby, the director of the UCSF Headache Center. Until the advancement of imaging technology in the 1990s, migraines were entirely invisible. But it also has to do with the fact that women most commonly inherit the disease. One out of four women will experience migraine in their lives, three times as many as men—likely because hormonal fluctuations are a major migraine trigger. “The lack of research throughout the 20th century,” says Dr. Alexander Mauskop, the director of the New York Headache Center, “is because people, then and now, underestimated migraines. They thought it was a disease of hysterical, neurotic women.” Only three hours are spent on headaches during four years of medical school. Less than a one percent of the NIH’s annual budget is dedicated to migraine research — $14 million, some 36 cents per sufferer.

That the medical community has (finally) effectively responded with a preventative, targeted treatment is incredibly good news to migraineurs everywhere. Still, there’s work to be done. “Many doctors — doctors! — still believe it’s a stress-related problem,” says Mauskop. “It’s a brain disorder. Period. And it’s important people think of it that way.”

Is It a Basilar Migraine? Or Just an Ice-Pick Headache?

Distinguishing between a migraine and a headache is pretty simple, actually. If the pain is located on one side of your head, and comes with nausea and a sensitivity to light or sound, well, that’s likely a migraine. During a migraine, the trigeminal nerve, which is responsible for feeling in the face, is stimulated–which causes the release of neurotransmitters, including one called CGRP. This, in turn, causes blood vessels that surround the brain to inflame and become sensitive. Headaches, on the other hand, are primarily caused by the tightening of the muscles in the neck and the head. Below, a sampling of the various(ly) awful subcategories.

Migraines

Migraine without aura: An incapacitating collection of symptoms that typically includes intense nausea, a severe throbbing pain on one side of the head, and sensitivity to light. As with all migraines, the nerve endings and tissue that surround the brain become swollen and a neurotransmitter called CGRP spikes.

Migraine with (sensory or visual) aura: The aura — which is experienced only by some 30 percent of migraine sufferers — is the collection of symptoms caused by hyperexcited nerves in the occipital lobe that happen before the headache begins. A typical aura presents as a loss of vision (or as seeing zigzags or sparks in the line of sight), lethargy, and an inability to speak clearly and articulately; it lasts up to an hour.

Basilar migraines: With these, the aura presents as dizziness, lack of coordination, and double vision. Afterward, there is often nausea and incapacitating pain in the head. Basilar migraines originate in the brainstem (the very bottom of the brain, which connects to the spinal cord) — which is why it is felt in the body.

Hemiplegic migraine: A very rare type of migraine whose aura resembles a stroke. Sufferers are struck with intense weakness in one side of the body, including the face, arm, and leg, and slurred speech and drowsiness, and are then hit with a debilitating, generally one-sided headache. These are primarily genetic — if you have them, your children have an extremely high chance of inheriting them — and they’re caused by mutated genes that affect communication between nerve cells.

Vestibular migraine: Often appearing without headaches; symptoms include intense dizziness, nausea and vomiting, balance problems, extreme motion sickness, and sensitivity to sound. It’s unclear exactly what causes this migraine, but it’s typically credited to misfires between nerve cells in the brain.

Abdominal migraine: Most often found in children, abdominal migraines are characterized by pain in the stomach that lasts from two to 72 hours, vomiting, frequent yawning, and loss of appetite. Doctors will diagnose this as migraine (rather than a stomach flu or Crohn’s disease) if the pain originates around the bellybutton and if the child has at least one parent with migraine.

Headaches

Tension-type headaches: The most common type of headache, it generally feels like having a tight band around the skull. They’re not made worse by physical activity and are caused by contracted scalp or neck muscles.

Cluster headaches: The most painful kind of headache; often called “suicide headaches.” They recur daily over a period of four to six weeks (a “cluster period”), and each last about 30 minutes to an hour. The pain is generally located behind one eye — people say it feels like “a hot poker.” Patients with cluster headaches often hit their head against the wall or with their fist, pace, scream, and occasionally have a change in personality.

New daily persistent headaches: A headache that starts one day in a person who does not have a history of migraine and never goes away. This usually begins with a cold or a flu but can also be caused by an infection or Lyme disease. The headache can range from mild to severe and generally feels like a tension-type headache.

Thunderclap headache: Headaches that strike suddenly like — as the name suggests — a clap of thunder. These headaches are rare, extremely painful, and can be accompanied by fever, and changes in speech. They can be a signifier of some rather alarming conditions, like blood clots in the brain, meningitis, or an ischemic stroke.

Me and My Migraine

Author Katy Schneider on what her migraines feel like, and how she copes.

… When I’m at work

Sometimes I’m typing an email and half of my computer screen disappears — just like that, in a split second. But there’s a protocol to follow: I reach for an Axert pill in my change purse and swallow it. Then I walk to my office’s wellness room, which has a recliner chair. I set a phone timer for 45 minutes, shut off the lights, and try to will myself to sleep. My right temple begins to pang, and I’m struck with nausea — but still, I won’t open my eyes, If I do, the whole room will be flooded with bubbling, zigzagging shapes. The aura peaks at 30 minutes and by 45 is usually gone. When I step out of the dark room, the light is blinding — still, the front desk is no longer swallowed by the aura. My parents’ apartment on the Upper West Side is a 25-minute subway ride from my office, so I get on the uptown 1 and plug my ears with my fingers. Taking a cab would be quieter, but during migraines my car sickness becomes unbearable. Once I got in a Lyft with a migraine; utterly wracked with headache and nausea, I got out and throw up in a trash can. At my parents’, the blinds are heavy and I take a two hour nap. When I wake, I sulk around a little and eat a sleeve of crackers. I always crave salt after a migraine — my doctor tells me it has something to do with my exhausted adrenal glands.

… When I’m sleeping

Sometimes I dream that I have a migraine. And then I wake up and realize the dream is real: Half my vision is swallowed, and my right temple is throbbing, which means I’m at least 30 minutes into an episode. To abort a migraine, you have to take your medication in the first five minutes; my window is gone. I fish around for my medicine, though I know it won’t work. The light is filtering through the windows, and I take half a Benadryl to help fall back asleep quicker. If the pain is too piercing, I’ll boil a pot of water and then stick a washcloth in it until it’s scorching hot and put it over my eyes. If I’m lucky, when my alarm goes off, my vision will have been restored and my headache reduced to a dull throb, and I’ll go to work feeling a little dissociated but okay: Those symptoms are called a postdrome; it feels like walking through a fog. But sometimes I wake and am just sick: I throw up when the light flashes through my blinds, the headache lodges itself in my temple.

… When I’m driving

In high school, I drove a half-hour to school every day on the I-95 in Connecticut. Sometimes I’d merge onto the four-lane freeway to realize, Well, I can’t see the freeway. When I’m driving and get a migraine, I jostle for my pills with my right hand and drive with my left. If the aura takes over quickly, and I’m far from where I’m going, I pull into a rest station and roll my seat all the way back and put a sweater over my eyes and set a timer on my phone and nap until the aura relents. If I’m close to home, I drive below 65; I try to watch the road though the cars are halved and the trees are halved and the whole of my vision is crossed with pesky, quivering lines of white light.

A Migraineurs Medicine Cabinet of Curiosities

The new preventative injectable medication is only for patients with frequent migraine. So here, the seizure meds, antidepressants, and cold cans of Coke that other sufferers have long been forced to turn to.

Photo: Joe McKendry

“I take gabapentin, a seizure medication, every day, and when I get a migraine, I take a triptan with coffee and two Advil and try to pass out as quickly as possible before I start throwing up. I used to take beta blockers — a blood-pressure medication — which didn’t work. I’ve taken nortriptyline, an anti-depression medication — that did very little.” —Zoe Raduns, migraine without aura

Illustration: Joe McKendry

“I take 60 mg. of antidepressant nortriptyline in the morning and 360 mg. of the blood-pressure medication verapamil at night. I do 200 mg. of vitamin B2 twice a day and also take a daily pill of turmeric, which has anti-inflammatory properties.” —Grace Gold, chronic migraine

Photo: Joe McKendry

“I take an ibuprofen suppository that has to be created specially by my pharmacy — if I try taking any pills, I throw up. It’s 500 mg. and torpedo-shaped.”  —Ethan Raduns-Silverstein, migraine with aura

Photo: Joe McKendry

“I used to get four migraines a month. They were super-intense — I started getting them when I was 10 years old. I would get visuals, then vomit, and then sleep about 12 hours. Then I got my daith — my inner ear — pierced, which I’d heard helped. The piercing worked for me almost immediately — I heard about it from a friend. I got it done two years ago and have only gotten about 15 migraines since.” —Grace Noe, migraine with aura

Photo: Joe McKendry

“Once, during one of the worst migraines I’ve ever had, I took two Tylenols, drank a big glass of water, and shotgunned a freezing cold Coke. I swear I felt 98 percent better in ten minutes. I was wide awake after that, but since the pain was dulled, I was able to relax.”  —Amy Pedulla, migraine without aura

Beverly Hills plastic surgeon William Binder is the guy who accidentally realized Botox worked for migraines.

“I told my neurologist friends, ‘I have a cure for migraine.’ And they said, ‘Yeah, sure Bill, it’s made of blue cheese.’ ”

“In the early ’90s, I was doing one of the first clinical trials on Botox for wrinkles in my office in Beverly Hills. The people in the trial, of course, are mostly women. And many of them told me, ‘Bill, my headaches are gone.’ My intellectual curiosity kicked in; in 1992, I decided to do a small trial in my office with migraine sufferers to test the theory. And I couldn’t believe the results — 55 patients over the two years I did this trial all had reduced migraine days. With no side effects. I put together a protocol, and called a couple of my neurologist friends. I said, ‘I have a cure for migraine.’ And they said ‘Yeah, sure, Bill, it’s made of blue cheese.’ Still: in September 1997, I presented all of my data to Allergan, the giant pharmaceutical company who manufactures Botox, and a couple of big-time neurologists, who thought it was completely ridiculous. But you couldn’t argue with the results. Now the drug is approved in over 40 countries, and Allergen has probably made $600 million off of it. But even today, the neurologists don’t like to mention my name so much. They feel disenfranchised because a Beverly Hills plastic surgeon discovered a remedy for migraine.”

Now (Finally) an Official Way to Prevent Migraines

It took thirty years. Now it’s here.

The news that the first drug, Aimovig, created to prevent migraine was approved by the FDA was announced late on a recent Thursday evening. And the migraine community — those who’ve long relied on vitamins, repurposed drugs with unpleasant side effects, and Eastern medicine (or some combination thereof) to manage their symptoms — was thrilled. Cautiously. “I cried,” said Wendy L., a long-term migraine sufferer. “But only a couple of tears, because I didn’t want to trigger a migraine.”

The drug takes the form of a single shot composed of a specially created antibody that targets a neurotransmitter called CGRP, whose levels spike in patients in the midst of a migraine. The injections modulate patients’ CGRP levels to prevent attacks from happening, instead of treating them — like T​riptans do — once they’ve already begun. The trials have been overwhelmingly successful — in one, patients with an average of eight monthly migraines found their episodes reduced by almost half by their fourth month of receiving the injections. The trial, it should be said, was aided by a powerful placebo effect: Patients who received the placebo had a reduction of some 1.7 migraine days a month.

So why did it take 30 years? For one, because back in the ’80s — when researchers Peter Goadsby and Lars Edvinsson initially discovered the relationship between CGRP and migraine — the medical community believed (incorrectly) that it was instead a neurotransmitter called Substance P that was responsible for migraine pain. “Substance P was very popular at the time,” says Goadsby. “So our research was regarded as — well, sort of nice, but not terribly important.” Still, Goadsby and Edvinsson forged ahead, and in 2004 they oversaw the development of a drug that blocked CGRP. “It was tested in patients that year,” says Edvinsson. “And was found to have fabulous effects against acute attacks of migraines. Only then did the drug industry, and everyone else, change focus.” A final hurdle came in 2009, once the drug had gotten to phase three of testing for FDA approval: Thirteen patients in the 1,200-person trial were found to have elevated liver enzyme counts. The trial was terminated, and the drug companies were forced to start from scratch. Which they did. The liver issue was sidestepped. “They changed the chemical structure of the it,” says Edvinsson. And it made it, once again, to stage three — and then on to approval. The fact that Aimovig works (and works well) continues to amaze Edvinsson and Goadsby both. “I’ve had patients who have gotten a single treatment and then didn’t get any more migraines,” says Goadsby. “Full stop. And then we saw them after six months, nine months, 12 months. And still no headaches.” Plus, he adds, the drug is taken monthly in a single shot, and has no side effects — a nice plus for patients accustomed to weight gain and nausea from antidepressants, forgetfulness and dry mouth from anticonvulsants, or the discomfort of receiving 31 shots of Botox to the head every 12 weeks.

Since 2013, four companies have been jockeying to get their version of the medicine on the market; Amgen and Novartis got in first, Lilly, Teva, and Alder are expected to announce FDA approval for their​s​ in the New Year. The issue now is accessibility: The first version of the drug is expensive: $6,900 annually, $575 a treatment — the others are likely to be priced similarly. And it’s still unclear whether insurers will pay. The process has been complicated, says Goadsby. But the drug is simple. “It’s the first time we have a migraine preventative for migraine patients,” he says. “And it works. And it’s really well-tolerated. There’s no penalty to taking it: You get better. That’s it.”

And Someone Who’s Already Tried It …

“I started the trial in 2014. I found out about it through a friend who is a research nurse. I’d been getting daily severe headaches essentially since I was 9 years old. They’re hereditary: My grandfather was actually trepanned, which means he had holes drilled in his skull. I’d just had to resign from my job at the Parks and Recreation Department, which I loved, because my migraines got too bad. I’d tried everything for them: I had a hysterectomy, because my migraines were so severe around my period. I was going to the ER twice a month for an IV infusion for the pain and nausea. Then I did Botox, beta blockers, antidepressants, all the anti-seizure medications — nothing worked. The Triptans I took as needed did help reduce the migraine, but they cause rebound headaches.

The first trial I got into was a double blind, so I didn’t know if I was actually getting the medicine. I was feeling a little better, but I was also very hopeful. After that finished, I got into a second trial — this was not double blind: I knew I was getting the medication, 70 mg., which is a relatively low dose. That’s when I started feeling better.

My migraines decreased about 20 percent after that first month. Which, when you’re getting daily migraines, is incredibly substantial. I was still having severe migraines; still going to the ER for infusions. But far less often. I auditioned for a play at a local theater. I could get out of bed.

I have a text thread with some fellow migraine sufferers, and when the news came out, I just began shaking with joy. We’ve all had so much false hope over the years and have all been through so much — we’re tentative. But excited.” —Elizabeth Roberts-ZibbelBowling Green, Ohio

*This article appears in the May 28, 2018, issue of New York Magazine. Subscribe Now!

Why Did It Take So Long to Figure Out Migraines?