AUTHOR COMMENTARIES

What drew you to study migraine?

I got into this field purely by accident. I had migraines, my mother had migraines, my grandmother had migraines. I didn’t even know I had them, despite the fact that I’m a neurologist!

When I was at Germantown Hospital, the head of the Physical Therapy department had bad migraines, and the whole department would come to a standstill when they happened—no one at Germantown knew how to treat them, there was no one in Philadelphia who knew how to treat them, and there was no one to refer anybody to, so we all got together and taught ourselves about migraine.

We were two neurologists, a psychologist, and a psychiatrist who got together on a regular basis and we would pitch patients to the group to try to figure out what to do with them. That’s how we started.

Is that how the clinic here at Jefferson got started?

We were at Germantown for about 20 years, and to advance the Headache Center, we moved en masse from Germantown to here—that’s how the clinical piece got started.

What happened with the research arm is we started to write up our observations and got involved in the guidelines for the American Academy of Neurology—these were national guidelines written with the Agency for Healthcare Research & Quality. We actually created evidence-based guidelines for the treatment of migraine headaches.

A lot of your highly cited papers deal heavily with the pharmacological prevention and treatment of migraine. How have these treatments advanced, particularly within the context of your own work?

When I started, the only treatments being studied were acute treatments. It seemed fairly obvious to me that a major problem with migraine headaches was not so much treating the acute attacks, but preventing the attacks from occurring, because most of the patients we saw were those patients with very frequent headaches, whose major problem was overuse of acute medicine.

So my major interest from the beginning was not so much treating the acute attack but preventing attacks from occurring.

How did you start looking for preventative treatments?

Mainly by analogy. We looked at drugs that were useful for other disorders, read the literature, etc. For example, we saw that many people believed that migraine and epilepsy were similar in some ways, so we started looking at drugs that were marketed for the treatment of epilepsy (Depakote [divalproex sodium]) and convinced the companies who made them to do controlled trials which helped get approval of these drugs as treatment for migraine. We did the same thing with Topamax (topiramate).

How many preventatives are there now?

There are only four drugs approved by the FDA: Depakote, Topamax, and two beta-blockers, propranolol and metoprolol. There was another drug that was approved but is no longer available in the US. Everything else used for migraine prevention is an off-label use.

I imagine it’s a long process to get a drug "on-label." I see you have some studies on Botox (botulinum toxin)—how is the process going for these studies?

Yes, we are currently doing studies on Botox for the treatment of migraine. So far, it’s looking like—though I can’t say for sure—it may be effective for patients with very frequent headaches. It seems to slow down the frequency of headaches, so patients who have the occasional headache may not be affected, but those with very frequent headaches would be. The action of the drug may be responsible for the mechanism that makes headaches more frequent, as opposed to the fundamental mechanism controlling migraine.

Of the various treatments, what are the advantages/disadvantages? Do any particular groups benefit more with one than the other? Do you prefer individualized treatment?

We prefer not to use opioids, simply because if you compare a triptan to an opioid, the opioids have many more side effects. The idea of treating a migraine headache is not merely to take away the pain, the disability, but to maintain the function of daily life. And when people pick opioids, they often get significant side effects that will prevent them from functioning. So we tend to use narcotics/opioids as mainly rescue therapy, to relieve the pain and suffering of patients who go to the emergency room, but not as a first-line treatment unless we can’t use anything else with that particular patient.

Triptans are clearly clinically effective—they work in most patients. The major problem is the cardiovascular warnings—people with cardiovascular risk factors are not a candidate for triptans. That’s why there are new drugs in development to get around this problem, such as CGRP receptor antagonists.

Several of your papers involve menstrual migraine—how exactly does this differ from other types of migraine?

It’s simply migraine that’s triggered by menses. Most women with migraine (60%) have menstrual migraine. It’s generally longer in duration, often more severe, and often refractory to treatment.

If you had unlimited resources at your disposal, is there a particular question about migraine you would research?

The fundamental issue as I see it is that we have a structural problem in the US. Medical schools and residencies in the US have nobody educating them in headache. There are really not enough people in the headache field to keep things going. Part of the problem, and one of the major limitations as far as I’m concerned, is that unlike other areas of neuroscience and medicine, there’s no solid base of funding.

So my wish would not be to just fund one project, but jump-start the entire field. That’s more important than just one project—one project is fine, but it doesn’t change the field. People with migraine are under-diagnosed and under-treated, because there’s nobody in med school to teach doctors about headache and no money to champion a residency program to teach doctors about the appropriate treatment of headache.

Stephen Silberstein, M.D., FACP
Headache Center
Department of Neurology
Thomas Jefferson University Hospital
Philadelphia, PA, USA