Headache Treatment


Saturday, March 26, 2011

Botox Approved by FDA for treatment of Chronic Migraine

Dr. Charles Matthews is a board certified neurologist and Director of the North Carolina Comprehensive Headache Clinic. Here is an interview by Health and Healing with Dr. Matthews about the recent FDA approval of Botox for chronic migraine follows.

Q- Dr. Matthews, can you tell us about Botox, and why it’s being used for the treatment of migraine headaches?

Dr. Matthews: Sure. But first, my usual caution: Botox was FDA approved for chronic migraine. if you have frequent headaches, they are likely to be migraine, but they may not bemigraine. I apologize if I can get tiresome on this point!

There are many causes of chronic headache. Other types of chronic headache include chronic or paroxysmal hemicrania, hypnic headache, cluster headache, primary thunderclap headache, spontaneous intracranial hypotension, benign intracranial hypertension, trigeminal neuralgia, and others.

Infections and inflammatory disorders like temporal arteritis can also cause chronic headache. Botox doesn’t help any of these conditions. Typically in these conditions a standard MRI will be negative, so you really should have a neurologist go over these possibilities with you. The Triangle area has many outstanding neurologists who are knowledgeable about headache.

Q- Maybe not migraine, got it. So, tell us about Botox for migraine!

Dr. Matthews: Botox is a trademark of Allergan, the pharmaceutical company that makes onabotulinumtoxinA for medical use. Botox received FDA approval for the treatment of chronic migraines in October of 2010. So, when I say “Botox”, I’m referring to that particular type of botulinum toxin.

Botulinum toxin is made by a bacterium, Clostridium botulinum, that causes botulism. Botulism is one of the great old medical diseases, not common now, but very dramatic and it played an important historical role in understanding neurophysiology. The word “botulism” derives from German for sausage, as I understand it; it was described in Germany when people became ill from bad sausages.

Clostridium is a family of bacteria that grow best in low oxygen environments. You may have heard of “C. difficile”, an infection that occurs in the bowel when someone has wiped out the normal bacteria there with antibiotics. That’s another closely related “anaerobic” bacterium. C. botulinum, the organism that makes Botox, grows in canned foods that weren’t adequately sterilized, like sausages and green beans.

Q- Why do bacteria make toxins?

Hey, that’s a great question! Bacteria as a group can reproduce very rapidly. Let’s say that a bacterium divides once every twelve hours...in a month, if you don’t have something constraining the growth, that means you will have 2 to the sixtieth bacteria. That’s a lot of bacteria! In very short order, the surface of the earth would be covered unless something happens. The reason this doesn’t happen is, partly, they run out of food, but mostly, bacteria make poisons to kill off their competitors. Sometimes the poisons cause problems for people.

Q- You’re kind of a geek, aren’t you? (laughing).

Dr. Matthews: You were the one who asked the question! (laughing).

Botulinim toxin is really a muscle relaxant. It has some other effects, but the one best understood is how it works to relax muscles. Nerve endings very close to the muscle surface secrete a chemical that tell the muscle to contract. The chemical is called acetylcholine, and it is squirted out of the nerve and sticks to the muscle at sites that are called acetylcholine receptors, and that tells the muscle contract.

Botox works at least partly as an injectible muscle relatant. When Botox is injected into the muscle, it binds to a receptor on the muscle surface, and stays there. It blocks the signal from the brain to make the muscle contract. The binding is like hair dye; it’s permanent, but after awhile the roots start showing! It’s the same with Botox; after awhile new receptors are made, so the Botox falls out with the receptor. There are no known permanent side effects of Botox.

The word “toxin” can be misleading. When properly injected in low doses, it doesn’t make you toxic all over; it’s just toxic to the acetylcholine receptor at the injection site, and then you grow new ones.

Q: How long does Botox last?

Dr. Matthews: New receptors are made after about three months, about the same length of time as it takes to make new red blood cells.

Q- How do you use Botox to treat migraine?

Dr. Matthews: It’s important to realize that Botox has only been shown to work for chronic migraine. “Chronic” means you have migraine headaches more than half the time (more than 14 days a month).

Q- What if the person has migraine headaches only 13 days/month?

Dr. Matthews: Good question! I think you’re turning into a geek yourself!

It’s a complicated question, and it’s under discussion among headache specialsts. But basically, “chronic migraine” is in important ways different from episodic migraine. I don’t believe there is any benefit at all from using Botox for headaches that occur on fewer than 15 days a month. So, if you’re thinking you could add just a few headache days to your count and get the magic Botox paid for, you’re wrong, I think. Don’t do it!

It isn’t that Botox will one day be seen to benefit episodic migraine, or that people with episodic migraine are getting shortchanged since Botox is not covered for them. It’s that it just doesn’t work with episodic migraine.

Q- What’s special about chronic migraine?

Dr. Matthews: Nothing definite, but this is what I think is happening. For many people, they start out having episodic migraine, maybe a few times a month, then a few times a week. What causes this transformation from episodic to chronic migraine? I personally think that classical conditioning, like Pavlov described, plays an important role in transformation to chronic migraine, and suppressing that conditioning with Botox can convert chronic migraine back to episodic migraine, hopefully the frequency you had migraines when you started. So, Botox may cause aremission of chronic migraine by keeping headaches suppressed for long periods of time.

I’ll caution here that long term remission of chronic migraine has not been adequately studies experimentally. But I’ve administered Botox about 800 times for migraine since 1993, and in my experience there has not been a single case of continued need for Botox beyond about three years. The most common is three applications, once every three months, and then we wait and see if they are still needed.

Q- What’s classical conditioning again?

Dr. Matthews: I knew it, you really are a geek!

Ivan Pavlov was a Russian psysiologist. You can read about him athttp://en.wikipedia.org/wiki/Ivan_Pavlov .He was the one who rang the bell when the dog was fed, and after awhile you didn’t need food, the dog salivated anyway when the bell rang.

In migraine, every time you have a headache attack, and something else happens at the same time, your brain learns to link these up. I think this is one reason (there are others) that people with migraine attacks eventually get neck pain- the neck “learns” that a migraine is coming, and starts to guard just like the dog learns to salivate when the bell rings. After awhile, the neck stays tight, and the brain learns this as a trigger for migraine. This mutual “conditioning” eventually leads to progression, with the neck pain triggering migraine, and the migraine triggering neck pain.

In general, people who have migraine usually have triggers- odors, weather, food, fatigue, menses. Sometimes they will run their lives trying to avoid all their triggers. They come to the headache clinic hoping I will help them identify all their triggers. Unfortunately, when the migraine is chronic, avoiding triggers is like arranging deck chairs on the Titanic. If you avoid one trigger, your brain will learn a new one.

So, in my view, Botox may work by suppressing chronic migraine for a sufficiently long period of time for your body to unlearn those classical conditioned responses.

Q- How well does Botox work to suppress chronic migraine?

Dr. Matthews: The available studies show only a modest effect, that continues to increase for about six months though the second administration. Longer outcomes haven’t been studied adequately.

The studies were done in specialty headache clinics. My colleague headache specialists that did this work, and the subsequent FDA recommendations, I think everyone did a terrific job here. The approved dose, and administration schedule, shows great thought. OK, I said it: I’m proud of the FDA on this one!

They did not look at how well this modest effect would hold up when used outside of headache centers, and I think it won’t work quite as well in the followup studies. So, I have some sympathy with the hesitancy of some insurers. On the other hand, combining Botox with other treatments, I expect, will work out much better than previous studies, since in my view the whole point is to suppress chronic migraine completely for months in an attempt to get a remission to episodic migraine. So, Botox for chronic migraine may work best in an overall headache program.

Combining properly chosen preventive medicines, treatment for factors that make migraines worse such as sleep disturbance and pain medication overuse, and nerve blocks when indicated, when combined have a high rate of success in inducing chronic migraine remission.

At the Headache Clinic, when treating chronic migraine we look down the road five years, sometimes twenty years. We want the patient to be way better for the long term than they would have been if they had not seen us.

I think treating chronic migraine with the goal of remission does people a lot of good. In the long term, less OTC painkillers that cause so many problems, fewer migraines, no lost days at work or with your family, hopefully few or no doctor visits for headache, better health overall.

And that’s what medicine is all about.


Dr. Charles Matthews was the 1978 Jefferson Fellow in Medicine at the University of Virginia.

You can make an appointment at the North Carolina Comprehensive Headache by calling 919 781 7423.