Botox and Other Off-Label Treatments for Migraines

Most migraine management is off-label, doctors say.

ByKIM CAROLLO, ABC News Medical Unit
September 2, 2010, 6:16 PM

Sept. 10, 2010 -- Migraine sufferers like Barbara Trupin, who endured the severe headaches weekly for almost 20 years, will often do anything to get relief from the severe pain and other disabling symptoms.

Although there are a few medications approved by the U.S. Food and Drug Administration for migraine treatment, there are dozens more off-label ones that doctors and patients resort to when those don't provide relief.

"People will take anything that works," said Dr. Joel Saper, a neurologist at the Michigan Headache and Neurological Institute.

One of the off-label treatments for migraine prevention that works for some sufferers is Botox.

"It can help some patients who have not responded to other treatments," said Dr. Robert Kaniecki, assistant professor of neurology and director of The Headache Center at the University of Pittsburgh. However, he said it's often a last resort for patients because insurance companies may not cover it unless a patient can prove all other medications have been ineffective.

Botox injections may be administered in a variety of places, depending on where the pain is.

"It can be given over the bridge of the nose, over the eyebrows, or the back of the neck or shoulders," said Dr. Alan Rapoport, clinical professor of neurology at the David Geffen School of Medicine at UCLA. "It works for three to four months and there aren't usually too many side effects."

Allergan, the company that makes Botox, recently agreed to pay $600 million to settle criminal and civil complaints over what the U.S. government said was illegal promotion of the product for unintended purposes, including headaches.

Botox was recently approved as a preventive migraine treatment in the United Kingdom, and will be up for review by the FDA in December for the same indication.

Trupin never tried Botox. Instead, she used another off-label but common drug - Tylenol. She took a hefty dose of eight Tylenol, which she said dulled her pain enough to be able to perform household chores and other tasks. She said she never sought medical advice because the eight Tylenol always helped.

Doctors say that eight Tylenol may be excessive and could be potentially toxic if taken weekly for a long time, as Trupin did. But they say using off-label medications and treatments is very common when nothing else works. They also say these medications and treatments are sometimes more effective than anything that's approved.

Most Migraine Treatments are Off-Label

Tylenol is just one commonly used off-label medication for migraines.

"NSAIDs [nonsteroidal anti-inflammatory drugs], such as ibuprofen or naproxen, if they are prescribed, are not approved for migraines," said Rapoport. He added that the over-the-counter medications Motrin Migraine and Excedrin Migraine are approved.

Calcium channel antagonists, which are more often used to treat conditions like high blood pressure and irregular heartbeat, are also used for migraines. These drugs include nifedipine (Procardia or Adalat), nicardipine (Cardene) and verapamil (Calan).

"Antidepressants, anti-seizure medications and beta-blockers are also used for prevention of migraines," said Kaniecki. He also said that many of these are off-label.

There are also vitamins, minerals and supplements often used to prevent migraines.

"We do suggest certain ones for headaches, such as vitamin B2 (riboflavin), magnesium, coenzyme Q10, butterbur and melatonin," said Rapoport.

Doctors also recommend behavioral techniques to prevent migraines, such as biofeedback and relaxation.

"When we treat difficult headaches, you really have to rely on both off- and on-label, since there aren't that many on-label drugs," said Saper.

The fact that there are so few approved medications doesn't surprise doctors.

"It's a very expensive process to get drugs approved, and the FDA is very strict," said Rapoport.

Migraines are a genetic disorder characterized by a severe, often-throbbing headache that's often accompanied by other symptoms, including sensitivity to light, nausea and vomiting.

Migraines typically start with something called a prodrome, which is a pre-headache phase that can start anywhere from several hours to several days before the onset of the headache. During prodrome, many people will experience a wide variety of sensations, including yawning, fatigue and depression. People tend to get migraines for most of their lives, and they can vary in frequency and severity.

Seven drugs are FDA-approved for acute treatment of migraines and four others for migraine prevention. Doctors say there are more than 30 other drugs they often prescribe or suggest that are off-label, but are sometimes more effective than the FDA-approved medications.

Among the approved acute treatment drugs are medications known as triptans, including Imitrex, Maxalt and Zomig. Excedrin Migraine is also approved, though doctors say it contains the same ingredients -- aspirin, acetaminophen and caffeine - as Extra Strength Excedrin.

The four FDA-approved preventive migraine treatments are propanolol (Inderal), timolol (Blocadren), divalproex sodium (Depakote) and topiramate (Topamax).

The Dangers of Migraine Medications

Opiates, such as Demerol, are also used for migraines. They are also off-label, and doctors say they may not be the best option.

"Opiates are approved for severe pain, but not migraines, and they don't work very well," said Rapoport.

They can also be dangerously habit-forming as migraine sufferers continue to take them but get no relief, said Saper.

Medication overuse, even when that medication doesn't include narcotics, is a common problem among migraine sufferers, doctors say.

"Most people with migraines realize it takes a lot to get it under control," said Kaniecki.

He added that there are two dangers of overtreatment - headaches can return, and too much of some medications can be toxic. Too much ibuprofen, for example, can cause kidney damage.

Overtreatment can be dangerous with drugs that are approved for migraines as well. Doctors say intake should be limited.

"If you take any of these drugs for aborting a headache more than three days a week, week after week and month after month, it will actually make headaches worse," said Saper. "That's the main cause of why headaches progress from occasional to frequent."

But for people who suffer from migraines, that's not their first concern.

"My headaches were so bad that all I could think about was getting rid of the pain. They lasted for 24 hours. I didn't care about anything else," said Trupin.