According to our January 2008 Special Topics
analysis of migraine research over the past decade, the
#5 is Dr. Stephen Silberstein, with 75
papers cited a total of 1,559 times. According
Essential Science IndicatorsSMfromThomson
Silberstein’s record includes 121 papers, the
majority of which are classified in the field of
Neuroscience & Behavior, cited a total of 2,224
times to date.
Dr. Silberstein received his doctor of medicine
degree in 1967 from the University of Pennsylvania,
where he also did his internship and residency. He
trained and did medical research at the National
Institutes of Mental Health. He currently serves on the
editorial boards of several professional publications
including Headache, Topics in Pain Management
and Cephalalagia. He is also a past
president and vice president of the Philadelphia
Dr. Silberstein has been the Director of the
Comprehensive Headache Center from its creation in 1982
at Germantown Hospital in Philadelphia to its current
home at Thomas Jefferson University in Philadelphia.
According to Jefferson’s website, the Center is
"one of a very few academic headache centers in the
country." It specializes in headache treatment,
education, and research.
Editorial Coordinator Jennifer Minnick
recently met with Dr. Silberstein at the Center to talk
about his highly cited career for
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
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
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.
paper with 247 cites to
Silberstein SD, US Headache Consortium,
Evidence-based guidelines for migraine
headache (an evidence-based review)
– report of the Quality Standards
Subcommittee of the American Academy of
55(6): 754-62, 26 September 2000.
Essential Science Indicators
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
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
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
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
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
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
Stephen Silberstein, M.D., FACP
Department of Neurology
Thomas Jefferson University Hospital
Philadelphia, PA, USA