May 21, 2025 • 57 mins
Doctor Carolyn Tran joins Neurologist Steven Toenjes to discuss migraines. Migraine is a complex brain disease affecting one in five women and one in ten men, with treatments ranging from traditional medications to cutting-edge therapies targeting specific pathways in the brain. The doctors talk about the causes - or lack thereof, the lack of treatment, and common misconceptions about what headaches should be classified as migraines. Dr. Toenjes explains the phases of migraine, including prodrome, aura, pain, and postdrome. Then the two doctors explore many treatment options, discussing the uses, benefits, and drawbacks of each class of treatment.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Announcer (00:00):
Welcome to the MedEvidence! podcast.
This episode is a rebroadcastfrom a live MedEvidence!
presentation.
Dr. Carolyn Tran (00:06):
Yes, thanks for coming.
So, while you're nourishingyour bodies, we're going to
exercise your brain a little bitby starting out with some
questions to get you thinkingabout migraines.
Okay, so which of the followingstatements is true about
migraines?
A migraine is just a reallybad headache.
(00:31):
A migraine aura is your brain'sway of previewing the next
episode of reality.
People with migraines have asecret antenna that picks up bad
weather forecasts a day early.
Now some of you with arthritiswill say that is definitely true
, or currently there are nocures available for migraines.
(00:53):
Anyone want to venture a guess?
Dr. Steven Toenjes (01:01):
Yeah, it's the last one that currently we
don't have a way to make someonewho is a migraine patient not
be a migraine patient.
Migraine, it turns out, is apolygenetic disorder Some 30 to
35 genes that are involved, andif we happen to inherit the
(01:23):
right set of genes and in theright environment, our brain
becomes capable of making whathappens in a migraine occur.
And while there are not curesfor that, there are a tremendous
number of extremely effectivetherapeutic options that help us
significantly mitigate theimpact of migraines on patients'
(01:45):
lives.
The secret antenna one, I think, is funny.
You know, it is actually one ofthe most common things that
migraine patients will tell usthat they can't actually predict
when they're going to have amigraine event, when barometric
pressure changes are occurring,particularly the dropping phase
(02:06):
of it, and so there's not reallyan antenna that's there, but
there probably is potentiallysomething for us to discover.
We know almost nothing aboutthat, though.
Dr. Carolyn Tran (02:18):
All right, and to bring you back to your
school days of multiple choicequestions.
Which of the following arepossible symptoms of a migraine
attack?
A nausea and vomiting.
B sensitivity to light, alsoknown as photophobia C.
Sensitivity to sound, alsoknown as phonophobia D.
(02:40):
A persistent fever.
E.
A, b and C, but there's also F.
All of the above?
Dr. Steven Toenjes (02:54):
Okay, you were saying it correctly
Dr. Carolyn Tran (02:55):
I heard E.
Dr. Steven Toenjes (02:57):
Hit it one more.
I think it says
Dr. Carolyn Tran (03:00):
There's A, b and C.
Dr. Steven Toenjes (03:01):
So those are the symptom complex nausea,
vomiting light, soundsensitivity particularly that
make people think something ismigrainous.
But not everybody has thesesymptoms.
80% of people will be lightsensitive and so just because
(03:24):
someone does not have lightsensitivity does not mean that
the headache is not a migraine.
But those are extremely commonaccompaniments so I think we can
move on from that.
Dr. Carolyn Tran (03:35):
Okay, so let's get into what are migraines.
Dr. Steven Toenjes (03:40):
So this is the World Health Organization's
definition, you know, a primaryheadache disorder that is in
most cases episodic, usuallylasting between four and 72
hours, with the things we justmentioned nausea, vomiting,
photophobia, phonophobiasometimes preceded by the aura
phase of a migraine.
(04:00):
That we'll talk a little bitmore about in detail in just a
little in subsequent slides.
A couple of words about thefirst sentence there a primary
headache disorder.
We categorize headaches andsplit them into two broadest
categories primary and secondaryheadache syndromes.
(04:22):
Secondary headaches have acause that can or needs to be
identified.
The example that I give topatients is a silly example.
If somebody hits you in thehead with a brick, that would
hurt.
If they did it every day, itwould hurt every day.
We could give you all theheadache medicines on the planet
, it would not fix that problem.
(04:42):
You would have to figure outthat somebody's hitting you in
the head with a brick and askthem to please stop Now.
Primary headache disorders don'thave a cause that can or needs
to be identified.
That doesn't mean there's not acause.
I alluded to the genetic causeearlier.
It's just that you can'tidentify the cause for primary
headache disorders and you don'tneed to, because there's
(05:04):
nothing you can do about that,and that's very frustrating for
patients and family members whosuffer from a recurrent,
oftentimes extremely severeheadache complaint, and nobody
really explains to patients whatthe cause is.
And so, with migraine being byfar the most common severe
(05:30):
primary headache disorder, themost common primary headache
disorder is tension headache,but the most common severe one
is migraine.
It's helpful for people tounderstand the difference
between primary and secondaryheadaches, and so we don't
necessarily need to be searchingfor the cause for why somebody
gets migraines.
People just get them
Dr. Carolyn Tran (05:53):
All right.
Dr. Steven Toenjes (05:53):
Yeah, sure, okay, you want me to keep going?
Dr. Carolyn Tran (05:57):
Yes, please
Dr. Steven Toenjes (05:57):
Okay.
So when we look at thefrequency, some epidemiologic
information about migraines,it's important for us to
understand that less than 50% ofpeople with migraines ever go
to the doctor and actually askfor help, and so most people
with migraines are neverdiagnosed with migraines.
(06:20):
90% of people affected havesome pretty severe impact on
their life.
In the United States, one ofthe more recent estimates on the
frequency in the US is morethan 39 million people have
migraines.
One way that I think is usefulto sort of think through the
(06:41):
epidemiologic information withmigraines is to understand how
frequently the disorder ispresent in men and women because
it's a little more frequent infemales than in men.
It's two to three times asfrequent in females.
One in five females is amigraine patient.
Dr. Carolyn Tran (06:59):
That takes us time for our next slide as well.
Dr. Steven Toenjes (07:01):
Yep, and one in ten males is a migraine
patient.
And so if we are experiencingheadaches and you are either a
male or a female, if they arebad headaches, as long as
they're not a secondary headachesyndrome, you're very likely
(07:21):
dealing with migraines.
The American MigrainePrevalence Study, which is a
little bit of a dated study, butit is actually our more recent
epidemiologic studies, are nottoo different than the data that
came from AMPP.
You know, 50% of severemigraineurs, you know, never had
(07:45):
a formal diagnosis of migrainesand that's a mixture of things
not going to the doctor, doctorsnot asking about the problem
and then oftentimes beingmisdiagnosed.
Actually, we the next statementthat says 12% were in the
(08:05):
American Migraine PrevalenceStudy were on adequate
preventive therapies.
In the eyes of a headachespecialist, that is 12% of
patients who we would suggestneed to be on preventive
medications.
12% of them were on preventivemedications, and so that's just
(08:25):
a data point pointing out how weare really not adequately
taking care of migraine in theUnited States, based on that
report card.
Dr. Carolyn Tran (08:35):
And since you mentioned migraines are
underdiagnosed and sometimeseven misdiagnosed.
Do you want to say a little bitabout the thing we've talked
about with patients saying Ihave a sinus headache.
I don't have migraines
Dr. Steven Toenjes (08:52):
So that would be something that you
would have come acrossfrequently in a family practice
and I mean the data on it are85% of what a physician has
diagnosed as sinus headache.
Eighty-five percent of that isall migraine.
Of course, sinus infectionsexist they do.
(09:13):
But I gave you the statisticson.
A diagnosis of sinus headacheis almost all migraine.
And that's a good example ofand one of the reasons why we
very frequently have referralsto the headache clinic from ENT
physicians who say there'snothing wrong with your sinuses.
(09:35):
This is go see the headachedoctor, but that's only true of
some headache or some ENTphysicians.
Some ENT physicians just saythere's nothing wrong with your
sinuses and then don't followthrough with it.
Go see the neurologist.
So that's a good point.
Dr. Carolyn Tran (09:54):
All right.
Dr. Steven Toenjes (09:56):
This is kind of a funny one.
When I get a migraine, I alwaysfollow the aspirin label take
two and keep away from children.
I think that you know this slideis here to kind of make a point
(10:18):
that there are a variety ofreasons.
There's a list of reasons whypatients don't go to the doctor
and complain about headaches andwhy doctors don't necessarily
ask about headache disorders.
And one big piece of the puzzleturns out to be the stigma that
surrounds a migraine diagnosis.
Historically, with the littlefunny business over to the side,
(10:40):
that's actually a commercial, amarketing piece.
When boredom and emotionalfatigue bring on housewife
headache, it's actually anadvertisement for aspirin,
anacin and those sorts of biasedapproaches, viewing a migraine
(11:09):
patient as perhaps havingsomething emotionally wrong with
them.
You know, I think has beeningrained in our society for
generations actually.
But we need to and it isappropriate to think of migraine
as a brain disease.
It is a brain disorder.
We understand it very well andit is every bit of brain disease
(11:35):
as Alzheimer's or Parkinson'sor multiple sclerosi.
?
Dr. Carolyn Tran (11:36):
Yes, and aren't we glad that research has
taken us away from thehousewife headache.
My husband and I had a goodlaugh about that last night.
Dr. Steven Toenjes (11:43):
Yeah, All right, so it sort of jumps into
a little bit of a differenttopic.
Obviously, migraine is morecommon in females, and one of
the more common scenarios that aperson is actually likely to
(12:06):
seek help is when migraines aretied with menstrual periods.
You probably experienced quitea bit of that with your family
practice.
Dr. Carolyn Tran (12:17):
Yes, and fortunately, just like we talked
about with sometimes beingmisdiagnosed, young women will
think it's oh, it's PMS, it'sjust PMS.
It's just part of what I haveto go through every month.
Dr. Steven Toenjes (12:28):
I would ask you a question.
When, seeing a young female whois having trouble with
premenstrual symptoms and alion's share of that is the
headache complaint of it, Behonest, internally do you sort
(12:50):
of think, oh brother, this isgoing to be tough.
Dr. Carolyn Tran (12:53):
It's going to be tough.
It is tough because you knowyou're asking patients then to
like track their periods, tracktheir headaches, track all their
symptoms, which is the lastthing they want to do at that
time.
Dr. Steven Toenjes (13:05):
Well, the menstrual migraine clinical
scenario is a difficult one.
The problem is is thefluctuations in hormones that
are occurring, primarily at thebeginning of menstrual flow
(13:31):
menstrual flow but also on day14, where ovulation occurs.
The swings in hormones that areoccurring just turn out to be a
really good way to trigger whatis capable of being triggered in
the brain of a migraine patient.
And while it's a prominenttrigger, that trigger is
sustained.
The hormone swings that occurare sustained for days in a row,
(13:53):
usually several days in a row,and so to get that migraine
process to shut off hashistorically been quite
challenging because it's aprolonged exposure to the
trigger.
We do have a handful of uniqueapproaches to specifically deal
(14:17):
with menstrual migraine, and itis actually very specifically
one of the topics of a currentlyongoing clinical trial at
Jacksonville Center for ClinicalResearch, and we're certainly a
part of and we're excited aboutparticipating in that, because
the menstrual migraine patientis a challenging patient and,
(14:40):
while we have several thingsthat we know of that can really
be helpful, we need to expandthat medicine cabinet up a
little bit to help patients withmenstrual migraines.
Dr. Carolyn Tran (14:52):
So, now that we've talked about one of the
subtypes, let's talk about howare migraines diagnosed?
Dr. Steven Toenjes (14:58):
So when you went through training, did
anybody ever talk aboutdiagnostic criteria for migraine
?
Dr. Carolyn Tran (15:07):
Very little.
Yeah, very little.
Dr. Steven Toenjes (15:09):
I would be surprised, if at all.
So in 1988 was the first timethat the International
Classification of HeadacheDisorders was devised by a
handful of really expertlifelong headache specialists,
(15:31):
and headache diagnostic criteriaexist in this body of
literature.
Its name is the InternationalClassification of Headache
Disorders.
You'll see it says ICHD-3.
It's been revised three timesnow since 1988.
You'll see, it says ICHD-3.
It's been revised three timesnow since 1988.
And it is a set of diagnosticcriteria for all of the headache
(15:52):
disorders that humansexperience.
And so this is just the listingof migraine's diagnostic
criteria.
So the first is that a personhas had at least five attacks
and the reason that that fiveattacks it really says it's five
attacks over a period, had atleast five attacks, and the
reason that that five attacks itreally says it's five attacks
(16:13):
over a period of at least sixmonths.
That's really addressing thepossibility that the patient in
front of you is a secondaryheadache syndrome patient.
If somebody's been having arecurrent problem for six months
, they probably don't have ahemorrhage in their brain or
something like that.
It's been going on for sixmonths and so the duration of it
, I think, is how long thesyndrome has been present, is
(16:34):
actually part of the criteria.
It turns out that how long aheadache lasts turns out to be a
really diagnostically usefulpiece of information.
Migraine, untreated orunsuccessfully treated, is
almost always going to lastbetween four hours and 72 hours.
So up to three days would bepretty typical of a migraine
(16:54):
syndrome.
The characteristics that you seelisted under C this is where I
think a lot of confusion arises.
So the characteristics of beingon one side of the head,
unilateral, pulsating in quality, moderate or severe in pain and
aggravated by routine physicalactivity it makes people need to
(17:16):
avoid routine physical activity.
You need to have two of those,and so if something is moderate
or severe in intensity and ispulsating and throbbing, it can
be anywhere on your head.
If it's unilateral andpulsating, it doesn't actually
(17:37):
need to be moderate or severe.
It could be mild, and so youreally just need two of those to
be positive or present for usto satisfy diagnostic criteria.
Then, lastly, under D, nauseaor vomiting, or light and sound
sensitivity, we have a lot ofconfusion with light and sound
(17:59):
sensitivity as well.
The light sensitivity, as anexample, exists in a spectrum.
There are some people in themidst of a migraine who are so
light sensitive they haveblackout curtains.
They've shoved towels in thecracks of the door so there's no
light coming through underneaththe door.
They're laying in their bedwith the pillow over their head
(18:23):
and it's still too bright.
There are some people withmigraines who, if they look at a
fluorescent light, will noticeit's just a little bit more
comfortable.
I agree it is a little bit morecomfortable.
That's light sensitivity.
Actions speak louder than wordsoften in this situation, a lot
of times people will say no, Idon't have migraines, I don't
(18:44):
have any light sensitivity.
And we'll say well, where doyou go when you have a migraine?
I go in my room, the lights onor off?
They're off.
That's light sensitivity.
Then E is, of course, notbetter accounted by some other
diagnosis.
In other words, it's not goingto satisfy migraine's diagnostic
criteria if it's not migraine.
Dr. Carolyn Tran (19:04):
Yes, right satisfy migraine's diagnostic
criteria if it's not migraineright, and you had mentioned
kind of the timeline there ofmigraine attacks.
Dr. Steven Toenjes (19:21):
Yeah, I think that something that we
have learned a lot more about isthat migraine exists in
different phases.
It's helpful to think ofmigraine as having different
phases of the disorder.
The painfully obvious painphase is the headache phase,
listed on the third column.
There, a quarter of migrainepatients are capable of also
(19:41):
having an aura phase.
Raise your hand if you've everheard of what a migraine aura
would be like.
So that's a lot of hands.
And so typically a migraine aurawould be a visual one, an
evolution of changing, evolvingover minutes, visual complaints
(20:02):
to one side or the other, orperhaps in the center of vision,
where a person will seescintillations or lights or
colors.
Some people will actually see akaleidoscope.
There are interesting visualphenomena that happen, that
spread and evolve and the personwill generally not be able to
(20:22):
see within the light or thevisual phenomenon that's
occurring.
Only a quarter of migrainepatients are going to be capable
of having aura.
You only need to have two aurasin your entire lifetime and
you're a migraine with aurapatient.
You can have 10,000 migraineswith no aura and two with an
(20:44):
aura.
You're a migraine with aurapatient.
It is interesting that aura canproduce any symptom your brain
can produce, which means auracan produce essentially any
symptom you can think of, but ittends to just produce the
visual symptom.
The second most common migraineaura symptom is an evolution of
(21:04):
hemibody numbness.
And the third most commonmigraine aura symptom is an
expressive aphasia, where aperson in the midst of the
migraine has words that theycan't get out, something that I
think we are starting to learn alittle bit more about is
actually the prodromal phase Now, while a quarter of patients
(21:26):
with migraine are capable ofhaving the aura phase, actually
most people with migraine have aprodromal phase.
These are symptoms likeirritability, building neck
stiffness, smoldering, buildinglight sensitivity.
There are behavioral changesthat occur.
People can be depressed.
(21:46):
A really common one thatconfuses people is insomnia.
A lot of people think, well, Ihad trouble sleeping last night
and that's why I have mymigraine today.
But realistically, oftentimesit's the reverse of that.
You had trouble sleepingbecause you were in your
(22:07):
migraine prodrome and themigraine process was already
unfolding.
The prodrome can last hours toas much as a day or two before
the pain phase will occur, andthen the postdrome that we'll
call, or often refer to, as amigraine hangover, and so
oftentimes patients will be justwashed out, could be sleepy,
(22:29):
very fatigued, after a migraineevent has the pain phase has
finished, and so we know themost about the pain phase.
We have learned a lot.
There's still things a lot thatwe don't understand about aura.
We know very little aboutprodrome and post-drome, but we
are learning a lot more aboutthose different phases.
Dr. Carolyn Tran (22:52):
And the scary thing about aura, because we'll
see that a lot through theemergency room, because some of
the symptoms you mentionedaphasia, not being able to get
those words out numbness andtingling.
As we all learn more aboutwarning signs of stroke, we're
seeing a lot of those patientsgo to the ER and sometimes
they're not getting thatfollow-up.
They're like oh, you don't havea stroke, go home.
(23:12):
It's like what about themigraine?
Dr. Steven Toenjes (23:14):
Yeah, and the way to really differentiate
the two stroke and TIA areprecipitous, maximal and onset
disorders that don't reallyevolve much.
When we block a blood vessel inour head, boom.
All of the symptoms are thereinstantaneously.
Migraine is an evolvingdisorder.
(23:35):
The visual phenomenon evolvesover minutes, generally last 10,
15, 20 minutes, perhaps as muchas an hour.
If the numbness is somethingthat the person experiences, it
will very commonly evolve in thesame way.
It will spread.
A person will literally feel itwalking down a portion of their
body and that will be afterthey had the visual symptoms,
(23:58):
and then the expressive aphasiacomponent of it will happen then
10 or 15 minutes after thenumbness symptoms have happened,
and generally it occurs in thatway.
Then also, if somebody wouldhave numbness or expressive
aphasia as an aura symptom, theywill also have had visual aura
(24:21):
in their past, and so that's animportant clinical point as well
.
So pathophysiology is somethingthat just really refers to.
What is it that we understandabout physiologically?
What's happening in our brainwhen you would have gone through
(24:43):
and I would have gone throughis responsible for the throbbing
component of migraine.
One interesting thing is, ifyou really try to carefully
(25:11):
investigate whether thethrobbing symptom coincides with
the pulse.
It does not.
Ah, yes, and so we actually havelearned a lot about what we
call our trigeminal vascularsystem.
We have a cranial nerve calledour trigeminal nerve.
It supplies essentiallyeverything from our neck up,
(25:37):
including our intracranialvasculature and the lining of
our brain, the meningeal liningof our brain.
And what we don't understand isreally what's the first step
that gets this system activated.
It is something that startswith trigeminal activation.
(25:59):
Exactly how that begins is whatwe don't know, but once it has
begun, then we understand thattrigeminal nerves release a
substance called calcitonin,gene-related peptide, I think
it's on the next slide.
Dr. Carolyn Tran (26:14):
Lots of real changes going on in the brain
there.
Dr. Steven Toenjes (26:17):
And so over.
On your left is a littlecartoon of a trigeminal nerve,
and the little purple dots arethis thing labeled CGRP or
calcitonin gene-related peptide.
It is something that ourtrigeminal nerves release out in
our meninges, the lining of ourbrain, and that self-stimulates
(26:40):
those trigeminal nerves to thensend pain signals back to our
brain in a positive feedbackloop that really just starts
like a snowball rolling down ahill, and so it's been very
exciting for us to learn aboutthe pathophysiology and then
start to devise specificmigraine therapeutics that have
(27:05):
been developed to veryspecifically block the function
of this neurotransmitter,calcitonin gene-related peptide.
Dr. Carolyn Tran (27:13):
And then can you talk a little bit about what
you know?
We're talking about treatmentshere, and what does the level A
evidence mean?
Dr. Steven Toenjes (27:21):
So level A evidence is just what we're
going to refer to, as we've gota substantial amount of
well-done studies at least acouple of well-done studies and
that they demonstrate prettyclearly that the treatment is
effective.
The best evidence is aplacebo-controlled, blinded,
(27:45):
randomized, controlled trial,and so if you've got a couple of
those and a treatment seems tobe positive, that's fairly
strong pieces of informationthat the medicine we're talking
about is actually effective, andwe'll call that level A
evidence.
And then level B is just a stepbelow that and level C is like
(28:06):
hey, we think it's probablybeneficial.
It's got a weak study or twothat back it up.
And so this slide refers toabortive treatment.
It's important with migrainetherapeutics to think through
the treatments and keep them intheir respective buckets, and
(28:28):
abortive treatments aretreatments that are designed to
abort the current headache thatyou have.
If I'm developing a headacheright now, I would like a drug X
, Y or Z or one of these on thislist.
Please go away.
Headache right now.
That's what we mean by abortivetreatment, and the other class
that's important to payattention to or think about is
(28:49):
preventive treatments.
Preventive treatments we'll getto in just a minute.
So here on our level A evidence.
Not all of the medicines withlevel A evidence that are
abortive are listed here, butthe purpose of this slide and we
don't need to go through all ofthese medications.
(29:11):
Medications.
Over on your right, the triptanmedications.
You'll notice the genericmedication there.
The root all ends in triptan.
Those were really kind of one ofthe first true
migraine-specific therapies.
Sumatriptan was FDA approved in1991, and there are seven
(29:38):
triptans.
All seven of them are genericas well, by the way, and so they
have been increasingly easy toobtain.
Dhe or dihydroergotamine is theparent chemical that the
triptans were really derivedfrom to try to make them more
safe and have fewer side effects.
(29:59):
One of the general pointsthrough these slides is for
people to not necessarily writedown or look at the specific
names, but to just take thegeneral point like well, there's
a lot of things on this slide.
We have a lot of treatments anda number of them are level A,
the CGRP-based drugs which havelevel A evidence we'll kind of
(30:22):
show later.
Dr. Carolyn Tran (30:23):
Yes, and you'll notice as we go through
the treatments that they'regetting a little bit more
specific for migraines, becausewe all know acetaminophen,
tylenol, aspirin, general painmedicines, right, but, like Dr.
Toenjes just mentioned, thetriptans, these tans on the
other side, those aremigraine-specific, so we're
going to go to the next slideand show you some more.
So these are the level Bevidence treatments.
Dr. Steven Toenjes (30:45):
You know.
I do think it's worthmentioning that over on the
right side.
A lot of these are nauseamedicines and the anti-emetics.
Some of the nausea medicines alot of people have heard of
Zofran or Ondansetron.
Notice it's not on the list.
(31:07):
Ondansetron is a very goodnausea medicine and if somebody
has a migraine, ondansetronreally may abort the nausea, but
it will never abort theheadache.
Some nausea medicines compazineand promethazine, or Phenergan
Reglan, which is metoclopramide.
Those medications are actuallysome of the most effective ways
to abort a migraine, not justthe nausea, they will abort the
(31:30):
pain and it's very specificallyone of the reasons why, if
someone shows up in theemergency room with an
intractable headache which isapproximately one in ten people
in an emergency room one of themost important things that
they're supposed to give you isone of these anti-emetics,
because they're not a narcoticand they are very, very
(31:53):
effective at aborting the painof a migraine.
That always seems to meforgotten.
Then the level C evidencemedications for abortive.
I'd just point out that thereare some narcotics on here and
then an oldie but goodie that'sbeen around for a long time.
(32:15):
The last one Butalbital mixedwith acetaminophen and caffeine.
That is a medicine that wascalled Fioricet In the headache
clinic that medicine we refer toas the F word.
(32:45):
One of the things that's trueabout abortive medications,
acute relief medications, is ifa migraine patient takes them
too frequently, the medicationwill backfire on them and in a
slow, smoldering fashion, slowly, progressively increase the
frequency and severity of theheadache syndrome and severity
of the headache syndrome and wecall that rebound phenomenon or
medication overuse headache.
And Fioricet said the F word.
Medication is one of the mostpotent medicines at doing that.
I'm not saying there's no usefor Butalbital containing
(33:07):
substances in the headacheclinic, but we always have to
understand and respect thefrequency with which we can use
that medicine and stay away fromprogressively worsening
someone's headache syndrome.
And it turns out somewherebetween four and six doses of
Butalbital containing substancesin a month crosses that line
(33:30):
and starts to be able to buildthe headache syndrome.
And so when we see patientsthat are on six to eight
Fioricet a day, those peoplehave a very serious medication
rebound problem.
Dr. Carolyn Tran (33:43):
Yes, and I do see that a lot in primary care
patients who come in who wantrefills of those medications
because they've been on them foryears and they want at least 30
a month.
Dr. Steven Toenjes (33:53):
Yeah.
Dr. Carolyn Tran (33:54):
And it's very hard to convince them that there
are better alternativetreatments these days.
Dr. Steven Toenjes (33:59):
Okay.
Dr. Carolyn Tran (34:01):
Yeah, so let's talk about preventive
treatments.
Dr. Steven Toenjes (34:04):
The goal of preventive medications now is
going to be to take the overallfrequency of the headache
disorder and reduce that,hopefully significantly, and
hopefully with either no sideeffects or tolerable side
effects.
I share with patients thatwe'll define what we mean by
(34:29):
success with a preventivemedication, and we define
success as at least a 50%reduction in headache frequency.
At least a 50% reduction inheadache frequency and either no
side effects or tolerable sideeffects.
And I think it's an importantthing for patients who
(34:51):
oftentimes have lost hopebecause they've tried a number
of things and have not hadsuccess.
We have a lot of medicationswhere the likelihood of success,
as I defined it, is high.
Indeed, there are a number ofmedications that we'll kind of
point out here where most peoplethat initiate them achieve
(35:13):
success in the way that Idefined it, meaning at least a
50% reduction.
Dr. Carolyn Tran (35:17):
Yes, and just like we talked about in that
first slide, there is no curebut there are preventive
treatments to kind of decreasethat frequency.
But keeping it realistic, maybea 50% decrease for not curing
it.
Dr. Steven Toenjes (35:34):
So the American Headache Society has
some guidance on when is it weshould be thinking about
preventive medications.
I think it's a busy slide, butthe easy way to think through
this is certainly if somebody'shaving four migraine events in a
month, if they're beyond that,we really need to be thinking
(35:55):
about prevention, or if thepatient has significant
disability related to theirheadache syndrome.
One of the things that has beena little bit eye-opening through
global burden of diseasestudies, it turns out that
(36:20):
migraine is number two on thelist of disorders that give us
years lived disabled.
It's only second to low backpain, and if I asked who in here
has low back pain, everybody'shand is going to go up.
Well, migraine is number two interms of for humans across the
planet Earth, it's the numbertwo disabling condition.
(36:42):
It has to do with its sheerfrequency.
If you look at females inchildbearing years, migraine is
by far number one, and so one ofthe focuses that's important is
to pay attention to theheadache syndrome's impact on a
person's ability to function intheir life, and if the headache
(37:05):
syndrome has a substantialimpact on the person's ability
to function, it's appropriate tothink about preventive
medications.
Dr. Carolyn Tran (37:13):
Yeah, and I think that's important.
The word syndrome is, if youthink about that slide that we
showed you earlier, we'retalking about the prodrome,
everything leading up, andthat's three, four days of your
life where you're notfunctioning at 100%.
Dr. Steven Toenjes (37:27):
And every once in a while it's not the
pain of migraine that is thedisabling part.
It certainly can be thevomiting, it can definitely be
the every once in a while I'llsee it be the post-drome or the
hangover, where someone justcan't, doesn't have enough
energy to even get out of bedfor an entire day after the pain
(37:48):
phase, and so sometimes thepain is only moderate and they
can function through that, butthey can't function through the
post-drone, and so understandinghow the different phases of the
migraine syndrome impact aperson's ability to function,
you know, I think is reallyreally important.
Dr. Carolyn Tran (38:05):
Yes, and that does relate to, you think, four
or more headaches.
It's four headaches a month andI'd want to take a medicine
every day to prevent it.
Well, when that prodrome andthat post-drome are affecting
your week, then that makes a bigdifference.
Dr. Steven Toenjes (38:21):
The same sort of designation, preventive
therapies of level A.
We don't necessarily need to gothrough all of these.
The CGRP-based drugs arepurposefully not on this list,
so there's even more that havelevel A evidence in terms of
prevention.
You'll see down at the bottom,onabotulinum toxin A that is
(38:43):
Botox.
That is a common that we seecommercials for, the up at the
top, Diproex, that's a seizuremedicine, Topiramate's a seizure
medicine, Metoprolol,Propranolol and Timolol those
are blood pressure medications.
So these are all medicationsthat through the years, you know
(39:07):
, patients and doctors havefigured out oh, when I use this
medication it really helps mymigraine syndrome.
They're not very specific tomigraines pathophysiology though
, and they've all been sort ofaccidentally discovered.
It is a true story that whenpeople I would guess you know
(39:31):
just historically mostly femalesgetting Botox for cosmetic
purposes Also females rememberthey're one in five is a
migraine patient that whenbotulinum toxin was being used
for cosmetic purposes, themigraine patients were coming
back saying you guys need tostudy this because my headaches
(39:53):
are gone and it is FDA approvedas one of our most effective
preventive agents, but sort ofaccidentally discovered and
Botox or botulinum toxininjections for migraine is why I
have to leave at a hard stop at1 o'clock because there will be
(40:13):
20 people waiting in the clinicfor their Botox injections
because they need them.
It really helps them and it isone that you can make the
statement most people getsuccess with this preventive
measure as I defined it.
Sometimes I think it is usefulto understand the other things
(40:35):
listed on this Realistically.
When we look at if I place apatient on tapiramate for
example, Topamax or Topiramatewhat's the likelihood that that
person will achieve success?
The answer is actually 20 to30%, and so most people are not
going to either tolerate orrespond to our more conventional
(41:00):
oral preventive agents in thepast, and that has produced a
lot of treatment failures andmigraine patients.
A lot of them have given uphope.
But I just alluded to botulinumtoxin injections in our newer
CGRP-based therapies.
(41:21):
You know really do have a muchhigher rate of efficacy and
better tolerance rates too.
Dr. Carolyn Tran (41:27):
Yes, yes, and some of those medicines.
The hard part is convincingpatients.
This is not a quick fix.
You're not going to take itthat first month and it's going
to change your life.
Dr. Steven Toenjes (41:36):
Yes, Topiramate.
Our Topimax studies wereactually very well done,
randomized controlled trials,and in their studies they're a
good example of what you'realluding to.
When you look at the Topiramatetrials, the first time point
that treatment and placebogroups start to split is four
(41:58):
weeks.
So a month is when they startto split and then if you follow
the split it keeps splitting for18 months and so it's a very
slow, smoldering response thatwe do await for as long as the
person's not having side effects.
Dr. Carolyn Tran (42:14):
Let's take a look at some more preventive
therapies that are out there.
Dr. Steven Toenjes (42:18):
So the things that we list as level B,
there are some really goodoldies but goodies, and the
purpose of this is not to reviewthem all, I do think, but to
just note that there's a lot.
But I do think that it'sworthwhile pointing out that
there's a couple over to theright that are not really
medicines.
Riboflavin is vitamin B2.
(42:41):
It does have some reasonableevidence level B evidence in
efficacy and migraine preventionand that is not a medication
and magnesium.
So those are supplements.
The feverfew is an herbal thingand so, just because we run
through medications and ourdiscussions are heavily weighted
(43:06):
towards them, you know thereare ways to try to achieve
success, certainly withoutthings that we would consider a
traditional medicine.
Level C I think everything onthis list does have at least
some weak evidence.
Candesartan is a blood pressuremedicine that folks in other
(43:30):
countries would have, actuallyon the level A category, but
again, just the general pointthat there are a lot of
medications in our medicine box.
I think we can go by that one.
Dr. Carolyn Tran (43:42):
Yes, let's talk about the newer treatments
out there.
Dr. Steven Toenjes (43:46):
Yeah, so the CGRP, or calcitonin
gene-related peptide antagonists.
We have Gepants, and so you seethe generic name for all of
these medications is going toend in Gepant, just like the
triptans do.
Rimegepant is Nurtec.
You see Lady Gaga's commercialswith that medication.
That is the medicine that'sactually being studied as part
(44:10):
of the menstrual migraine trialthat we have ongoing.
Atogepant is Qulipta.
You do see commercials withQulipta and Ubrelvy or
ubrogepant.
We aren't seeing Zavzpret orzavegepent, which is a nasal
spray that doesn't have any realcommercials out yet.
(44:33):
If you pay attention to theQulipta commercials, the
atogepant commercials, you'llnotice that they'll give a
marketing piece.
They'll say a chance atheadache freedom, and so, while
there aren't cures, there arereasonable percentages of
(44:55):
patients that, as we initiatesome of these medicines like
Qulipta, they're literallycapable of going an entire month
with no headache and they mayhave started with 20 migraine
days in a month, and so the FDAlets them make that statement.
You know, the chance forheadache freedom.
Dr. Carolyn Tran (45:18):
You know the chance for headache freedom and
you want to talk a little bitabout like why this was so
different from some of thosetriptans that we had talked
about.
You know those Imatrex, Zomig,those older ones.
Dr. Steven Toenjes (45:26):
You know, there are some vascular risks
that are associated with thetriptans.
They do bind to receptors thatare on some of our blood vessels
and make them spasm a littlebit, including coronary arteries
and intracranial arteries.
The spasm is very minimal, butthere's at least theoretical
vascular risks with the triptans, and those risks don't really
(45:49):
exist with the Gepants.
They do not cause any vasospasmat all.
They prevent the dilatation ofblood vessels that occurs during
a migraine, but that's verydifferent than producing a spasm
, and so we have thought of themas extremely well-tolerated and
very safe medications.
Dr. Carolyn Tran (46:08):
Yes, because a lot of times with the triptans
we weren't able to even use themin patients who had any risk
factors for heart disease.
You know the pharmacist wouldgive us a call back.
Are you sure?
This patient has high bloodpressure.
They have coronary heartdisease already and this gave us
a whole new set of medicines toput in our toolbox as well.
And this was exciting for usbecause Jacksonville Center for
(46:32):
Clinical Research actually wasinvolved in some of the studies
that involved the calcitoningene-related peptide antagonists
before they were on the market.
So that's always exciting forme to see those now be available
to patients.
Dr. Steven Toenjes (46:44):
Yeah, we were part of atogepant study.
Dr. Carolyn Tran (46:46):
Yes, yeah
Dr. Steven Toenjes (46:48):
And a number of the self-administered
injectable antibodies, and sothere are other CGRP antagonist
therapies that are preventivetherapies.
They are self-administeredinjectables that someone injects
every 28 days, so it's not apill that they have to take and
(47:09):
they are extremelywell-tolerated.
They're listed over to theright.
Amavig, which was a renumab,was the first FDA-approved
CGRP-based drug, and that was in2018.
And the other four areextremely effective.
I use them every day, all fourof them, and all four of them.
(47:30):
I can say the same statement interms of, you know, most
patients get success, as Idefined, success with prevention
, and so it's nice for patientsto have, you know, a pretty
substantial list the CGRP-basedantibodies Qulipta and Nurtec,
or atogepant, rimegepant, aswell as Botox.
(47:53):
Those are all our medicinesthat you, medicines that most
people actually tolerate quitewell and respond to very, very
well.
Dr. Carolyn Tran (48:01):
Yes, and don't let the name monoclonal
antibodies scare you.
Many of you may have alreadyexperienced some of these with
cholesterol medications that arealready on the market.
It's kind of using the sametechnology there you know
(48:22):
technology there.
The
Dr. Steven Toenjes (48:23):
.
That is a very unique uhmedication.
Its name is trade name israyval.
It's the way to think of Reyvow, which is not really.
It's a Eli Lilly drug, butthey're not really marketing it
much at all.
It's actually a really goodmedication.
It functions very much liketriptans, but it only binds to a
very specific serotonergicreceptor and it produces no
vasospasm whatsoever, so it'slike a triptan that does not
(48:45):
have the cardiovascular risk.
It does make people sleepy andthe FDA required a
recommendation that someone notdrive for eight hours after
taking the dose and I think thatEli Lilly said well, we're not
going to make that much money onit, so they don't market it and
you don't see commercials forReyvow very much, but it is an
extremely beneficial drug thatsometimes is the solution to
(49:08):
somebody's migraine abortivetreatment.
Yeah, so one of the more commontreatments for chronic migraine
patients certainly is Botox,which the generic of Botox is
onabotulinum toxin A.
There are multiple botulinumtoxins.
(49:29):
Just Botox happens to beonabotulinum toxin A.
It is something.
That's a procedure, though, andyou see pictured the little
dummy head down at the bottom.
The little dots that you see onthat head are the location of
the injections for a migraineprotocol injection.
(49:50):
If you count them up, it's 31injection sites and has been FDA
approved for chronic migrainesince 2010.
And millions of people havebeen given this medication.
It's been around a long timedecades before it was, you know,
a long time before it was evenFDA approved for migraine and,
(50:11):
as mentioned, is one of our mosteffective preventive treatments
.
Dr. Carolyn Tran (50:15):
So each time one of your patients comes in,
are they getting an injection atevery single little red dot
there?
Dr. Steven Toenjes (50:21):
Yes, 31 shots
Dr. Carolyn Tran (50:22):
31 each time.
Dr. Steven Toenjes (50:26):
Yes, and every three months.
Dr. Carolyn Tran (50:28):
Every three months.
Dr. Steven Toenjes (50:28):
Yes, and if my scheduling is such that
they're going to be late by aweek, believe me, they are
complaining about it.
They're beating the door downto come and get their treatment
because after two, two and ahalf months it starts fading out
and they feel their migrainesyndrome coming back, and so
(50:49):
nobody misses their Botoxappointments.
Nobody likes getting 31 shotsin their head, and so the fact
that anybody comes back at allis a testament to the efficacy
of the medicine.
Dr. Carolyn Tran (51:01):
That is true
Dr. Steven Toenjes (51:02):
As a matter of fact, in private practice we
never even needed to confirmBotox appointments.
Nobody would miss their Botoxappointment.
Dr. Carolyn Tran (51:10):
Do they have amazing foreheads?
Dr. Steven Toenjes (51:13):
We're not doing that.
We don't do it for cosmeticpurposes.
There are a variety of othertherapies where this is not an
exhaustive review of migrainetreatments.
Down at the bottom there aredevice therapies,
neuromodulation devices that canbe effective.
(51:34):
A lot of people have heardabout the Cefaly device.
They're difficult to use in theUnited States, mainly because
we can't get insurance to coverany of this stuff, despite there
being efficacy and safe.
These are safe treatments.
But just because, even ifsomebody has literally been
through all medicines and isreally still struggling, there
(51:58):
are still other treatmentoptions that we really kind of
haven't talked too much about.
And the neuromodulation devicesare, I think you know, really
really beneficial.
And behavioral management youknow one of the most important
things.
I give a sheet on behavioralmodifications that can be
(52:19):
beneficial in migraine patients.
Every new patient that comes inis going to get a handout on
the kind of behaviors that theyneed to be paying attention to
and those kinds of changesthings like staying hydrated,
not abusing caffeine, sleepingenough hours in the day an
important one, keeping yourcircadian rhythm the same,
(52:41):
meaning going to bed and gettingup at the same time every day,
trying to get some exercisethese minor things can really
dramatically impact headachefrequency in a migraine patient.
Dr. Carolyn Tran (52:53):
Yeah, and you just touched on those.
I just want to have a questionfor you, Dr.
Toenjes.
In terms of Memantine, some ofyou may recognize this
medication.
We often use it for Alzheimer's.
Dr. Steven Toenjes (53:06):
Yes, it's FDA approved to improve
cognition in moderate to severeAlzheimer's disease.
That's its FDA approval.
But there's some pretty goodstudies on its efficacy in
migraine prevention and itsmechanism of action.
You would guess it may beeffective and actually,
(53:29):
historically and I know this maysound weird before we got rid
of the pregnancy class system Memantine medications, was
pregnancy class B, so it was amigraine preventive agent that,
at least theoretically, we wouldthink would be safe to use
during pregnancy.
I've never done that, but that'sactually the, it is actually
(53:51):
true.
So I would say the biofeedbackand relaxation training you know
these are along the lines ofsort of the behavioral
modifications that we mentioned.
Relaxation training actuallyhas some pretty strong data in
functioning as both abortive andmigraine prevention.
(54:14):
Yoga as an exercisespecifically seems to be pretty
special in terms of its benefitfor migraine patients.
I've always thought that it'snot just the exercise of yoga,
that it's beneficial.
Yoga includes some relaxation,and so I've always wondered if
(54:35):
that's the reason why, you know,adopting a yoga habit as long
as you're careful with your neckand migraine patients, you know
is a very, very good idea.
Dr. Carolyn Tran (54:45):
Is that the relaxation of the muscles that's
giving you the benefit?
Dr. Steven Toenjes (54:48):
Absolutely, and that's what biofeedback is.
We'll just talk briefly about.
Sometimes it's worthwhile forpatients to actually kind of
formally track exactly how oftenthey're having headaches.
I like the Migraine Buddy one,but there are a variety of
tracking apps.
You know a calendar is atracking app that works as well,
(55:13):
but sometimes it's eye-openingto see really how often
somebody's having headaches andhow often they're taking
medications, and those kind oftracking apps really do exist,
and so I guess in conclusionsyeah, so what I hope that people
(55:36):
can take from this is anunderstanding of really how
common migraine is one in fivefemales, one in 10 males.
It is an extremely disablingdisorder that we usually don't
go to our doctor and seekattention or ask for help, and
(55:57):
actually usually our doctor doesnot ask us if we have headache
problems.
And so increasing awareness ofthe people sitting in the room
and your family members that arearound you If you're aware of
someone who has a significantimpact in their life from a
(56:18):
headache disorder, your job nowis to educate them about the
fact that there really are a lotof treatments and even
treatments that we're stillstudying and that are on the
horizon.
Keep the thoughts about thedifferent therapeutic,
supportive and preventivestrategies separate and walk
(56:41):
away from this understandingthat there are actually a lot of
therapies that we have in ourtoolbox to help mitigate the
disabling brain disease that wecall migraine.
Announcer (56:53):
Thanks for joining the MedEvidence! podcast.
To learn more, head over toMedEvidence.
com.
Call migraine.
Welcome to the MedEvidence! podcast.
This episode is a rebroadcastfrom a live MedEvidence!
presentation.
Dr. Carolyn Tran (00:06):
Yes, thanks for coming.
So, while you're nourishingyour bodies, we're going to
exercise your brain a little bitby starting out with some
questions to get you thinkingabout migraines.
Okay, so which of the followingstatements is true about
migraines?
A migraine is just a reallybad headache.
(00:31):
A migraine aura is your brain'sway of previewing the next
episode of reality.
People with migraines have asecret antenna that picks up bad
weather forecasts a day early.
Now some of you with arthritiswill say that is definitely true
, or currently there are nocures available for migraines.
(00:53):
Anyone want to venture a guess?
Dr. Steven Toenjes (01:01):
Yeah, it's the last one that currently we
don't have a way to make someonewho is a migraine patient not
be a migraine patient.
Migraine, it turns out, is apolygenetic disorder Some 30 to
35 genes that are involved, andif we happen to inherit the
(01:23):
right set of genes and in theright environment, our brain
becomes capable of making whathappens in a migraine occur.
And while there are not curesfor that, there are a tremendous
number of extremely effectivetherapeutic options that help us
significantly mitigate theimpact of migraines on patients'
(01:45):
lives.
The secret antenna one, I think, is funny.
You know, it is actually one ofthe most common things that
migraine patients will tell usthat they can't actually predict
when they're going to have amigraine event, when barometric
pressure changes are occurring,particularly the dropping phase
(02:06):
of it, and so there's not reallyan antenna that's there, but
there probably is potentiallysomething for us to discover.
We know almost nothing aboutthat, though.
Dr. Carolyn Tran (02:18):
All right, and to bring you back to your
school days of multiple choicequestions.
Which of the following arepossible symptoms of a migraine
attack?
A nausea and vomiting.
B sensitivity to light, alsoknown as photophobia C.
Sensitivity to sound, alsoknown as phonophobia D.
(02:40):
A persistent fever.
E.
A, b and C, but there's also F.
All of the above?
Dr. Steven Toenjes (02:54):
Okay, you were saying it correctly
Dr. Carolyn Tran (02:55):
I heard E.
Dr. Steven Toenjes (02:57):
Hit it one more.
I think it says
Dr. Carolyn Tran (03:00):
There's A, b and C.
Dr. Steven Toenjes (03:01):
So those are the symptom complex nausea,
vomiting light, soundsensitivity particularly that
make people think something ismigrainous.
But not everybody has thesesymptoms.
80% of people will be lightsensitive and so just because
(03:24):
someone does not have lightsensitivity does not mean that
the headache is not a migraine.
But those are extremely commonaccompaniments so I think we can
move on from that.
Dr. Carolyn Tran (03:35):
Okay, so let's get into what are migraines.
Dr. Steven Toenjes (03:40):
So this is the World Health Organization's
definition, you know, a primaryheadache disorder that is in
most cases episodic, usuallylasting between four and 72
hours, with the things we justmentioned nausea, vomiting,
photophobia, phonophobiasometimes preceded by the aura
phase of a migraine.
(04:00):
That we'll talk a little bitmore about in detail in just a
little in subsequent slides.
A couple of words about thefirst sentence there a primary
headache disorder.
We categorize headaches andsplit them into two broadest
categories primary and secondaryheadache syndromes.
(04:22):
Secondary headaches have acause that can or needs to be
identified.
The example that I give topatients is a silly example.
If somebody hits you in thehead with a brick, that would
hurt.
If they did it every day, itwould hurt every day.
We could give you all theheadache medicines on the planet
, it would not fix that problem.
(04:42):
You would have to figure outthat somebody's hitting you in
the head with a brick and askthem to please stop Now.
Primary headache disorders don'thave a cause that can or needs
to be identified.
That doesn't mean there's not acause.
I alluded to the genetic causeearlier.
It's just that you can'tidentify the cause for primary
headache disorders and you don'tneed to, because there's
(05:04):
nothing you can do about that,and that's very frustrating for
patients and family members whosuffer from a recurrent,
oftentimes extremely severeheadache complaint, and nobody
really explains to patients whatthe cause is.
And so, with migraine being byfar the most common severe
(05:30):
primary headache disorder, themost common primary headache
disorder is tension headache,but the most common severe one
is migraine.
It's helpful for people tounderstand the difference
between primary and secondaryheadaches, and so we don't
necessarily need to be searchingfor the cause for why somebody
gets migraines.
People just get them
Dr. Carolyn Tran (05:53):
All right.
Dr. Steven Toenjes (05:53):
Yeah, sure, okay, you want me to keep going?
Dr. Carolyn Tran (05:57):
Yes, please
Dr. Steven Toenjes (05:57):
Okay.
So when we look at thefrequency, some epidemiologic
information about migraines,it's important for us to
understand that less than 50% ofpeople with migraines ever go
to the doctor and actually askfor help, and so most people
with migraines are neverdiagnosed with migraines.
(06:20):
90% of people affected havesome pretty severe impact on
their life.
In the United States, one ofthe more recent estimates on the
frequency in the US is morethan 39 million people have
migraines.
One way that I think is usefulto sort of think through the
(06:41):
epidemiologic information withmigraines is to understand how
frequently the disorder ispresent in men and women because
it's a little more frequent infemales than in men.
It's two to three times asfrequent in females.
One in five females is amigraine patient.
Dr. Carolyn Tran (06:59):
That takes us time for our next slide as well.
Dr. Steven Toenjes (07:01):
Yep, and one in ten males is a migraine
patient.
And so if we are experiencingheadaches and you are either a
male or a female, if they arebad headaches, as long as
they're not a secondary headachesyndrome, you're very likely
(07:21):
dealing with migraines.
The American MigrainePrevalence Study, which is a
little bit of a dated study, butit is actually our more recent
epidemiologic studies, are nottoo different than the data that
came from AMPP.
You know, 50% of severemigraineurs, you know, never had
(07:45):
a formal diagnosis of migrainesand that's a mixture of things
not going to the doctor, doctorsnot asking about the problem
and then oftentimes beingmisdiagnosed.
Actually, we the next statementthat says 12% were in the
(08:05):
American Migraine PrevalenceStudy were on adequate
preventive therapies.
In the eyes of a headachespecialist, that is 12% of
patients who we would suggestneed to be on preventive
medications.
12% of them were on preventivemedications, and so that's just
(08:25):
a data point pointing out how weare really not adequately
taking care of migraine in theUnited States, based on that
report card.
Dr. Carolyn Tran (08:35):
And since you mentioned migraines are
underdiagnosed and sometimeseven misdiagnosed.
Do you want to say a little bitabout the thing we've talked
about with patients saying Ihave a sinus headache.
I don't have migraines
Dr. Steven Toenjes (08:52):
So that would be something that you
would have come acrossfrequently in a family practice
and I mean the data on it are85% of what a physician has
diagnosed as sinus headache.
Eighty-five percent of that isall migraine.
Of course, sinus infectionsexist they do.
(09:13):
But I gave you the statisticson.
A diagnosis of sinus headacheis almost all migraine.
And that's a good example ofand one of the reasons why we
very frequently have referralsto the headache clinic from ENT
physicians who say there'snothing wrong with your sinuses.
(09:35):
This is go see the headachedoctor, but that's only true of
some headache or some ENTphysicians.
Some ENT physicians just saythere's nothing wrong with your
sinuses and then don't followthrough with it.
Go see the neurologist.
So that's a good point.
Dr. Carolyn Tran (09:54):
All right.
Dr. Steven Toenjes (09:56):
This is kind of a funny one.
When I get a migraine, I alwaysfollow the aspirin label take
two and keep away from children.
I think that you know this slideis here to kind of make a point
(10:18):
that there are a variety ofreasons.
There's a list of reasons whypatients don't go to the doctor
and complain about headaches andwhy doctors don't necessarily
ask about headache disorders.
And one big piece of the puzzleturns out to be the stigma that
surrounds a migraine diagnosis.
Historically, with the littlefunny business over to the side,
(10:40):
that's actually a commercial, amarketing piece.
When boredom and emotionalfatigue bring on housewife
headache, it's actually anadvertisement for aspirin,
anacin and those sorts of biasedapproaches, viewing a migraine
(11:09):
patient as perhaps havingsomething emotionally wrong with
them.
You know, I think has beeningrained in our society for
generations actually.
But we need to and it isappropriate to think of migraine
as a brain disease.
It is a brain disorder.
We understand it very well andit is every bit of brain disease
(11:35):
as Alzheimer's or Parkinson'sor multiple sclerosi.
?
Dr. Carolyn Tran (11:36):
Yes, and aren't we glad that research has
taken us away from thehousewife headache.
My husband and I had a goodlaugh about that last night.
Dr. Steven Toenjes (11:43):
Yeah, All right, so it sort of jumps into
a little bit of a differenttopic.
Obviously, migraine is morecommon in females, and one of
the more common scenarios that aperson is actually likely to
(12:06):
seek help is when migraines aretied with menstrual periods.
You probably experienced quitea bit of that with your family
practice.
Dr. Carolyn Tran (12:17):
Yes, and fortunately, just like we talked
about with sometimes beingmisdiagnosed, young women will
think it's oh, it's PMS, it'sjust PMS.
It's just part of what I haveto go through every month.
Dr. Steven Toenjes (12:28):
I would ask you a question.
When, seeing a young female whois having trouble with
premenstrual symptoms and alion's share of that is the
headache complaint of it, Behonest, internally do you sort
(12:50):
of think, oh brother, this isgoing to be tough.
Dr. Carolyn Tran (12:53):
It's going to be tough.
It is tough because you knowyou're asking patients then to
like track their periods, tracktheir headaches, track all their
symptoms, which is the lastthing they want to do at that
time.
Dr. Steven Toenjes (13:05):
Well, the menstrual migraine clinical
scenario is a difficult one.
The problem is is thefluctuations in hormones that
are occurring, primarily at thebeginning of menstrual flow
(13:31):
menstrual flow but also on day14, where ovulation occurs.
The swings in hormones that areoccurring just turn out to be a
really good way to trigger whatis capable of being triggered in
the brain of a migraine patient.
And while it's a prominenttrigger, that trigger is
sustained.
The hormone swings that occurare sustained for days in a row,
(13:53):
usually several days in a row,and so to get that migraine
process to shut off hashistorically been quite
challenging because it's aprolonged exposure to the
trigger.
We do have a handful of uniqueapproaches to specifically deal
(14:17):
with menstrual migraine, and itis actually very specifically
one of the topics of a currentlyongoing clinical trial at
Jacksonville Center for ClinicalResearch, and we're certainly a
part of and we're excited aboutparticipating in that, because
the menstrual migraine patientis a challenging patient and,
(14:40):
while we have several thingsthat we know of that can really
be helpful, we need to expandthat medicine cabinet up a
little bit to help patients withmenstrual migraines.
Dr. Carolyn Tran (14:52):
So, now that we've talked about one of the
subtypes, let's talk about howare migraines diagnosed?
Dr. Steven Toenjes (14:58):
So when you went through training, did
anybody ever talk aboutdiagnostic criteria for migraine
?
Dr. Carolyn Tran (15:07):
Very little.
Yeah, very little.
Dr. Steven Toenjes (15:09):
I would be surprised, if at all.
So in 1988 was the first timethat the International
Classification of HeadacheDisorders was devised by a
handful of really expertlifelong headache specialists,
(15:31):
and headache diagnostic criteriaexist in this body of
literature.
Its name is the InternationalClassification of Headache
Disorders.
You'll see it says ICHD-3.
It's been revised three timesnow since 1988.
You'll see, it says ICHD-3.
It's been revised three timesnow since 1988.
And it is a set of diagnosticcriteria for all of the headache
(15:52):
disorders that humansexperience.
And so this is just the listingof migraine's diagnostic
criteria.
So the first is that a personhas had at least five attacks
and the reason that that fiveattacks it really says it's five
attacks over a period, had atleast five attacks, and the
reason that that five attacks itreally says it's five attacks
(16:13):
over a period of at least sixmonths.
That's really addressing thepossibility that the patient in
front of you is a secondaryheadache syndrome patient.
If somebody's been having arecurrent problem for six months
, they probably don't have ahemorrhage in their brain or
something like that.
It's been going on for sixmonths and so the duration of it
, I think, is how long thesyndrome has been present, is
(16:34):
actually part of the criteria.
It turns out that how long aheadache lasts turns out to be a
really diagnostically usefulpiece of information.
Migraine, untreated orunsuccessfully treated, is
almost always going to lastbetween four hours and 72 hours.
So up to three days would bepretty typical of a migraine
(16:54):
syndrome.
The characteristics that you seelisted under C this is where I
think a lot of confusion arises.
So the characteristics of beingon one side of the head,
unilateral, pulsating in quality, moderate or severe in pain and
aggravated by routine physicalactivity it makes people need to
(17:16):
avoid routine physical activity.
You need to have two of those,and so if something is moderate
or severe in intensity and ispulsating and throbbing, it can
be anywhere on your head.
If it's unilateral andpulsating, it doesn't actually
(17:37):
need to be moderate or severe.
It could be mild, and so youreally just need two of those to
be positive or present for usto satisfy diagnostic criteria.
Then, lastly, under D, nauseaor vomiting, or light and sound
sensitivity, we have a lot ofconfusion with light and sound
(17:59):
sensitivity as well.
The light sensitivity, as anexample, exists in a spectrum.
There are some people in themidst of a migraine who are so
light sensitive they haveblackout curtains.
They've shoved towels in thecracks of the door so there's no
light coming through underneaththe door.
They're laying in their bedwith the pillow over their head
(18:23):
and it's still too bright.
There are some people withmigraines who, if they look at a
fluorescent light, will noticeit's just a little bit more
comfortable.
I agree it is a little bit morecomfortable.
That's light sensitivity.
Actions speak louder than wordsoften in this situation, a lot
of times people will say no, Idon't have migraines, I don't
(18:44):
have any light sensitivity.
And we'll say well, where doyou go when you have a migraine?
I go in my room, the lights onor off?
They're off.
That's light sensitivity.
Then E is, of course, notbetter accounted by some other
diagnosis.
In other words, it's not goingto satisfy migraine's diagnostic
criteria if it's not migraine.
Dr. Carolyn Tran (19:04):
Yes, right satisfy migraine's diagnostic
criteria if it's not migraineright, and you had mentioned
kind of the timeline there ofmigraine attacks.
Dr. Steven Toenjes (19:21):
Yeah, I think that something that we
have learned a lot more about isthat migraine exists in
different phases.
It's helpful to think ofmigraine as having different
phases of the disorder.
The painfully obvious painphase is the headache phase,
listed on the third column.
There, a quarter of migrainepatients are capable of also
(19:41):
having an aura phase.
Raise your hand if you've everheard of what a migraine aura
would be like.
So that's a lot of hands.
And so typically a migraine aurawould be a visual one, an
evolution of changing, evolvingover minutes, visual complaints
(20:02):
to one side or the other, orperhaps in the center of vision,
where a person will seescintillations or lights or
colors.
Some people will actually see akaleidoscope.
There are interesting visualphenomena that happen, that
spread and evolve and the personwill generally not be able to
(20:22):
see within the light or thevisual phenomenon that's
occurring.
Only a quarter of migrainepatients are going to be capable
of having aura.
You only need to have two aurasin your entire lifetime and
you're a migraine with aurapatient.
You can have 10,000 migraineswith no aura and two with an
(20:44):
aura.
You're a migraine with aurapatient.
It is interesting that aura canproduce any symptom your brain
can produce, which means auracan produce essentially any
symptom you can think of, but ittends to just produce the
visual symptom.
The second most common migraineaura symptom is an evolution of
(21:04):
hemibody numbness.
And the third most commonmigraine aura symptom is an
expressive aphasia, where aperson in the midst of the
migraine has words that theycan't get out, something that I
think we are starting to learn alittle bit more about is
actually the prodromal phase Now, while a quarter of patients
(21:26):
with migraine are capable ofhaving the aura phase, actually
most people with migraine have aprodromal phase.
These are symptoms likeirritability, building neck
stiffness, smoldering, buildinglight sensitivity.
There are behavioral changesthat occur.
People can be depressed.
(21:46):
A really common one thatconfuses people is insomnia.
A lot of people think, well, Ihad trouble sleeping last night
and that's why I have mymigraine today.
But realistically, oftentimesit's the reverse of that.
You had trouble sleepingbecause you were in your
(22:07):
migraine prodrome and themigraine process was already
unfolding.
The prodrome can last hours toas much as a day or two before
the pain phase will occur, andthen the postdrome that we'll
call, or often refer to, as amigraine hangover, and so
oftentimes patients will be justwashed out, could be sleepy,
(22:29):
very fatigued, after a migraineevent has the pain phase has
finished, and so we know themost about the pain phase.
We have learned a lot.
There's still things a lot thatwe don't understand about aura.
We know very little aboutprodrome and post-drome, but we
are learning a lot more aboutthose different phases.
Dr. Carolyn Tran (22:52):
And the scary thing about aura, because we'll
see that a lot through theemergency room, because some of
the symptoms you mentionedaphasia, not being able to get
those words out numbness andtingling.
As we all learn more aboutwarning signs of stroke, we're
seeing a lot of those patientsgo to the ER and sometimes
they're not getting thatfollow-up.
They're like oh, you don't havea stroke, go home.
(23:12):
It's like what about themigraine?
Dr. Steven Toenjes (23:14):
Yeah, and the way to really differentiate
the two stroke and TIA areprecipitous, maximal and onset
disorders that don't reallyevolve much.
When we block a blood vessel inour head, boom.
All of the symptoms are thereinstantaneously.
Migraine is an evolvingdisorder.
(23:35):
The visual phenomenon evolvesover minutes, generally last 10,
15, 20 minutes, perhaps as muchas an hour.
If the numbness is somethingthat the person experiences, it
will very commonly evolve in thesame way.
It will spread.
A person will literally feel itwalking down a portion of their
body and that will be afterthey had the visual symptoms,
(23:58):
and then the expressive aphasiacomponent of it will happen then
10 or 15 minutes after thenumbness symptoms have happened,
and generally it occurs in thatway.
Then also, if somebody wouldhave numbness or expressive
aphasia as an aura symptom, theywill also have had visual aura
(24:21):
in their past, and so that's animportant clinical point as well
.
So pathophysiology is somethingthat just really refers to.
What is it that we understandabout physiologically?
What's happening in our brainwhen you would have gone through
(24:43):
and I would have gone throughis responsible for the throbbing
component of migraine.
One interesting thing is, ifyou really try to carefully
(25:11):
investigate whether thethrobbing symptom coincides with
the pulse.
It does not.
Ah, yes, and so we actually havelearned a lot about what we
call our trigeminal vascularsystem.
We have a cranial nerve calledour trigeminal nerve.
It supplies essentiallyeverything from our neck up,
(25:37):
including our intracranialvasculature and the lining of
our brain, the meningeal liningof our brain.
And what we don't understand isreally what's the first step
that gets this system activated.
It is something that startswith trigeminal activation.
(25:59):
Exactly how that begins is whatwe don't know, but once it has
begun, then we understand thattrigeminal nerves release a
substance called calcitonin,gene-related peptide, I think
it's on the next slide.
Dr. Carolyn Tran (26:14):
Lots of real changes going on in the brain
there.
Dr. Steven Toenjes (26:17):
And so over.
On your left is a littlecartoon of a trigeminal nerve,
and the little purple dots arethis thing labeled CGRP or
calcitonin gene-related peptide.
It is something that ourtrigeminal nerves release out in
our meninges, the lining of ourbrain, and that self-stimulates
(26:40):
those trigeminal nerves to thensend pain signals back to our
brain in a positive feedbackloop that really just starts
like a snowball rolling down ahill, and so it's been very
exciting for us to learn aboutthe pathophysiology and then
start to devise specificmigraine therapeutics that have
(27:05):
been developed to veryspecifically block the function
of this neurotransmitter,calcitonin gene-related peptide.
Dr. Carolyn Tran (27:13):
And then can you talk a little bit about what
you know?
We're talking about treatmentshere, and what does the level A
evidence mean?
Dr. Steven Toenjes (27:21):
So level A evidence is just what we're
going to refer to, as we've gota substantial amount of
well-done studies at least acouple of well-done studies and
that they demonstrate prettyclearly that the treatment is
effective.
The best evidence is aplacebo-controlled, blinded,
(27:45):
randomized, controlled trial,and so if you've got a couple of
those and a treatment seems tobe positive, that's fairly
strong pieces of informationthat the medicine we're talking
about is actually effective, andwe'll call that level A
evidence.
And then level B is just a stepbelow that and level C is like
(28:06):
hey, we think it's probablybeneficial.
It's got a weak study or twothat back it up.
And so this slide refers toabortive treatment.
It's important with migrainetherapeutics to think through
the treatments and keep them intheir respective buckets, and
(28:28):
abortive treatments aretreatments that are designed to
abort the current headache thatyou have.
If I'm developing a headacheright now, I would like a drug X
, Y or Z or one of these on thislist.
Please go away.
Headache right now.
That's what we mean by abortivetreatment, and the other class
that's important to payattention to or think about is
(28:49):
preventive treatments.
Preventive treatments we'll getto in just a minute.
So here on our level A evidence.
Not all of the medicines withlevel A evidence that are
abortive are listed here, butthe purpose of this slide and we
don't need to go through all ofthese medications.
(29:11):
Medications.
Over on your right, the triptanmedications.
You'll notice the genericmedication there.
The root all ends in triptan.
Those were really kind of one ofthe first true
migraine-specific therapies.
Sumatriptan was FDA approved in1991, and there are seven
(29:38):
triptans.
All seven of them are genericas well, by the way, and so they
have been increasingly easy toobtain.
Dhe or dihydroergotamine is theparent chemical that the
triptans were really derivedfrom to try to make them more
safe and have fewer side effects.
(29:59):
One of the general pointsthrough these slides is for
people to not necessarily writedown or look at the specific
names, but to just take thegeneral point like well, there's
a lot of things on this slide.
We have a lot of treatments anda number of them are level A,
the CGRP-based drugs which havelevel A evidence we'll kind of
(30:22):
show later.
Dr. Carolyn Tran (30:23):
Yes, and you'll notice as we go through
the treatments that they'regetting a little bit more
specific for migraines, becausewe all know acetaminophen,
tylenol, aspirin, general painmedicines, right, but, like Dr.
Toenjes just mentioned, thetriptans, these tans on the
other side, those aremigraine-specific, so we're
going to go to the next slideand show you some more.
So these are the level Bevidence treatments.
Dr. Steven Toenjes (30:45):
You know.
I do think it's worthmentioning that over on the
right side.
A lot of these are nauseamedicines and the anti-emetics.
Some of the nausea medicines alot of people have heard of
Zofran or Ondansetron.
Notice it's not on the list.
(31:07):
Ondansetron is a very goodnausea medicine and if somebody
has a migraine, ondansetronreally may abort the nausea, but
it will never abort theheadache.
Some nausea medicines compazineand promethazine, or Phenergan
Reglan, which is metoclopramide.
Those medications are actuallysome of the most effective ways
to abort a migraine, not justthe nausea, they will abort the
(31:30):
pain and it's very specificallyone of the reasons why, if
someone shows up in theemergency room with an
intractable headache which isapproximately one in ten people
in an emergency room one of themost important things that
they're supposed to give you isone of these anti-emetics,
because they're not a narcoticand they are very, very
(31:53):
effective at aborting the painof a migraine.
That always seems to meforgotten.
Then the level C evidencemedications for abortive.
I'd just point out that thereare some narcotics on here and
then an oldie but goodie that'sbeen around for a long time.
(32:15):
The last one Butalbital mixedwith acetaminophen and caffeine.
That is a medicine that wascalled Fioricet In the headache
clinic that medicine we refer toas the F word.
(32:45):
One of the things that's trueabout abortive medications,
acute relief medications, is ifa migraine patient takes them
too frequently, the medicationwill backfire on them and in a
slow, smoldering fashion, slowly, progressively increase the
frequency and severity of theheadache syndrome and severity
of the headache syndrome and wecall that rebound phenomenon or
medication overuse headache.
And Fioricet said the F word.
Medication is one of the mostpotent medicines at doing that.
I'm not saying there's no usefor Butalbital containing
(33:07):
substances in the headacheclinic, but we always have to
understand and respect thefrequency with which we can use
that medicine and stay away fromprogressively worsening
someone's headache syndrome.
And it turns out somewherebetween four and six doses of
Butalbital containing substancesin a month crosses that line
(33:30):
and starts to be able to buildthe headache syndrome.
And so when we see patientsthat are on six to eight
Fioricet a day, those peoplehave a very serious medication
rebound problem.
Dr. Carolyn Tran (33:43):
Yes, and I do see that a lot in primary care
patients who come in who wantrefills of those medications
because they've been on them foryears and they want at least 30
a month.
Dr. Steven Toenjes (33:53):
Yeah.
Dr. Carolyn Tran (33:54):
And it's very hard to convince them that there
are better alternativetreatments these days.
Dr. Steven Toenjes (33:59):
Okay.
Dr. Carolyn Tran (34:01):
Yeah, so let's talk about preventive
treatments.
Dr. Steven Toenjes (34:04):
The goal of preventive medications now is
going to be to take the overallfrequency of the headache
disorder and reduce that,hopefully significantly, and
hopefully with either no sideeffects or tolerable side
effects.
I share with patients thatwe'll define what we mean by
(34:29):
success with a preventivemedication, and we define
success as at least a 50%reduction in headache frequency.
At least a 50% reduction inheadache frequency and either no
side effects or tolerable sideeffects.
And I think it's an importantthing for patients who
(34:51):
oftentimes have lost hopebecause they've tried a number
of things and have not hadsuccess.
We have a lot of medicationswhere the likelihood of success,
as I defined it, is high.
Indeed, there are a number ofmedications that we'll kind of
point out here where most peoplethat initiate them achieve
(35:13):
success in the way that Idefined it, meaning at least a
50% reduction.
Dr. Carolyn Tran (35:17):
Yes, and just like we talked about in that
first slide, there is no curebut there are preventive
treatments to kind of decreasethat frequency.
But keeping it realistic, maybea 50% decrease for not curing
it.
Dr. Steven Toenjes (35:34):
So the American Headache Society has
some guidance on when is it weshould be thinking about
preventive medications.
I think it's a busy slide, butthe easy way to think through
this is certainly if somebody'shaving four migraine events in a
month, if they're beyond that,we really need to be thinking
(35:55):
about prevention, or if thepatient has significant
disability related to theirheadache syndrome.
One of the things that has beena little bit eye-opening through
global burden of diseasestudies, it turns out that
(36:20):
migraine is number two on thelist of disorders that give us
years lived disabled.
It's only second to low backpain, and if I asked who in here
has low back pain, everybody'shand is going to go up.
Well, migraine is number two interms of for humans across the
planet Earth, it's the numbertwo disabling condition.
(36:42):
It has to do with its sheerfrequency.
If you look at females inchildbearing years, migraine is
by far number one, and so one ofthe focuses that's important is
to pay attention to theheadache syndrome's impact on a
person's ability to function intheir life, and if the headache
(37:05):
syndrome has a substantialimpact on the person's ability
to function, it's appropriate tothink about preventive
medications.
Dr. Carolyn Tran (37:13):
Yeah, and I think that's important.
The word syndrome is, if youthink about that slide that we
showed you earlier, we'retalking about the prodrome,
everything leading up, andthat's three, four days of your
life where you're notfunctioning at 100%.
Dr. Steven Toenjes (37:27):
And every once in a while it's not the
pain of migraine that is thedisabling part.
It certainly can be thevomiting, it can definitely be
the every once in a while I'llsee it be the post-drome or the
hangover, where someone justcan't, doesn't have enough
energy to even get out of bedfor an entire day after the pain
(37:48):
phase, and so sometimes thepain is only moderate and they
can function through that, butthey can't function through the
post-drone, and so understandinghow the different phases of the
migraine syndrome impact aperson's ability to function,
you know, I think is reallyreally important.
Dr. Carolyn Tran (38:05):
Yes, and that does relate to, you think, four
or more headaches.
It's four headaches a month andI'd want to take a medicine
every day to prevent it.
Well, when that prodrome andthat post-drome are affecting
your week, then that makes a bigdifference.
Dr. Steven Toenjes (38:21):
The same sort of designation, preventive
therapies of level A.
We don't necessarily need to gothrough all of these.
The CGRP-based drugs arepurposefully not on this list,
so there's even more that havelevel A evidence in terms of
prevention.
You'll see down at the bottom,onabotulinum toxin A that is
(38:43):
Botox.
That is a common that we seecommercials for, the up at the
top, Diproex, that's a seizuremedicine, Topiramate's a seizure
medicine, Metoprolol,Propranolol and Timolol those
are blood pressure medications.
So these are all medicationsthat through the years, you know
(39:07):
, patients and doctors havefigured out oh, when I use this
medication it really helps mymigraine syndrome.
They're not very specific tomigraines pathophysiology though
, and they've all been sort ofaccidentally discovered.
It is a true story that whenpeople I would guess you know
(39:31):
just historically mostly femalesgetting Botox for cosmetic
purposes Also females rememberthey're one in five is a
migraine patient that whenbotulinum toxin was being used
for cosmetic purposes, themigraine patients were coming
back saying you guys need tostudy this because my headaches
(39:53):
are gone and it is FDA approvedas one of our most effective
preventive agents, but sort ofaccidentally discovered and
Botox or botulinum toxininjections for migraine is why I
have to leave at a hard stop at1 o'clock because there will be
(40:13):
20 people waiting in the clinicfor their Botox injections
because they need them.
It really helps them and it isone that you can make the
statement most people getsuccess with this preventive
measure as I defined it.
Sometimes I think it is usefulto understand the other things
(40:35):
listed on this Realistically.
When we look at if I place apatient on tapiramate for
example, Topamax or Topiramatewhat's the likelihood that that
person will achieve success?
The answer is actually 20 to30%, and so most people are not
going to either tolerate orrespond to our more conventional
(41:00):
oral preventive agents in thepast, and that has produced a
lot of treatment failures andmigraine patients.
A lot of them have given uphope.
But I just alluded to botulinumtoxin injections in our newer
CGRP-based therapies.
(41:21):
You know really do have a muchhigher rate of efficacy and
better tolerance rates too.
Dr. Carolyn Tran (41:27):
Yes, yes, and some of those medicines.
The hard part is convincingpatients.
This is not a quick fix.
You're not going to take itthat first month and it's going
to change your life.
Dr. Steven Toenjes (41:36):
Yes, Topiramate.
Our Topimax studies wereactually very well done,
randomized controlled trials,and in their studies they're a
good example of what you'realluding to.
When you look at the Topiramatetrials, the first time point
that treatment and placebogroups start to split is four
(41:58):
weeks.
So a month is when they startto split and then if you follow
the split it keeps splitting for18 months and so it's a very
slow, smoldering response thatwe do await for as long as the
person's not having side effects.
Dr. Carolyn Tran (42:14):
Let's take a look at some more preventive
therapies that are out there.
Dr. Steven Toenjes (42:18):
So the things that we list as level B,
there are some really goodoldies but goodies, and the
purpose of this is not to reviewthem all, I do think, but to
just note that there's a lot.
But I do think that it'sworthwhile pointing out that
there's a couple over to theright that are not really
medicines.
Riboflavin is vitamin B2.
(42:41):
It does have some reasonableevidence level B evidence in
efficacy and migraine preventionand that is not a medication
and magnesium.
So those are supplements.
The feverfew is an herbal thingand so, just because we run
through medications and ourdiscussions are heavily weighted
(43:06):
towards them, you know thereare ways to try to achieve
success, certainly withoutthings that we would consider a
traditional medicine.
Level C I think everything onthis list does have at least
some weak evidence.
Candesartan is a blood pressuremedicine that folks in other
(43:30):
countries would have, actuallyon the level A category, but
again, just the general pointthat there are a lot of
medications in our medicine box.
I think we can go by that one.
Dr. Carolyn Tran (43:42):
Yes, let's talk about the newer treatments
out there.
Dr. Steven Toenjes (43:46):
Yeah, so the CGRP, or calcitonin
gene-related peptide antagonists.
We have Gepants, and so you seethe generic name for all of
these medications is going toend in Gepant, just like the
triptans do.
Rimegepant is Nurtec.
You see Lady Gaga's commercialswith that medication.
That is the medicine that'sactually being studied as part
(44:10):
of the menstrual migraine trialthat we have ongoing.
Atogepant is Qulipta.
You do see commercials withQulipta and Ubrelvy or
ubrogepant.
We aren't seeing Zavzpret orzavegepent, which is a nasal
spray that doesn't have any realcommercials out yet.
(44:33):
If you pay attention to theQulipta commercials, the
atogepant commercials, you'llnotice that they'll give a
marketing piece.
They'll say a chance atheadache freedom, and so, while
there aren't cures, there arereasonable percentages of
(44:55):
patients that, as we initiatesome of these medicines like
Qulipta, they're literallycapable of going an entire month
with no headache and they mayhave started with 20 migraine
days in a month, and so the FDAlets them make that statement.
You know, the chance forheadache freedom.
Dr. Carolyn Tran (45:18):
You know the chance for headache freedom and
you want to talk a little bitabout like why this was so
different from some of thosetriptans that we had talked
about.
You know those Imatrex, Zomig,those older ones.
Dr. Steven Toenjes (45:26):
You know, there are some vascular risks
that are associated with thetriptans.
They do bind to receptors thatare on some of our blood vessels
and make them spasm a littlebit, including coronary arteries
and intracranial arteries.
The spasm is very minimal, butthere's at least theoretical
vascular risks with the triptans, and those risks don't really
(45:49):
exist with the Gepants.
They do not cause any vasospasmat all.
They prevent the dilatation ofblood vessels that occurs during
a migraine, but that's verydifferent than producing a spasm
, and so we have thought of themas extremely well-tolerated and
very safe medications.
Dr. Carolyn Tran (46:08):
Yes, because a lot of times with the triptans
we weren't able to even use themin patients who had any risk
factors for heart disease.
You know the pharmacist wouldgive us a call back.
Are you sure?
This patient has high bloodpressure.
They have coronary heartdisease already and this gave us
a whole new set of medicines toput in our toolbox as well.
And this was exciting for usbecause Jacksonville Center for
(46:32):
Clinical Research actually wasinvolved in some of the studies
that involved the calcitoningene-related peptide antagonists
before they were on the market.
So that's always exciting forme to see those now be available
to patients.
Dr. Steven Toenjes (46:44):
Yeah, we were part of atogepant study.
Dr. Carolyn Tran (46:46):
Yes, yeah
Dr. Steven Toenjes (46:48):
And a number of the self-administered
injectable antibodies, and sothere are other CGRP antagonist
therapies that are preventivetherapies.
They are self-administeredinjectables that someone injects
every 28 days, so it's not apill that they have to take and
(47:09):
they are extremelywell-tolerated.
They're listed over to theright.
Amavig, which was a renumab,was the first FDA-approved
CGRP-based drug, and that was in2018.
And the other four areextremely effective.
I use them every day, all fourof them, and all four of them.
(47:30):
I can say the same statement interms of, you know, most
patients get success, as Idefined, success with prevention
, and so it's nice for patientsto have, you know, a pretty
substantial list the CGRP-basedantibodies Qulipta and Nurtec,
or atogepant, rimegepant, aswell as Botox.
(47:53):
Those are all our medicinesthat you, medicines that most
people actually tolerate quitewell and respond to very, very
well.
Dr. Carolyn Tran (48:01):
Yes, and don't let the name monoclonal
antibodies scare you.
Many of you may have alreadyexperienced some of these with
cholesterol medications that arealready on the market.
It's kind of using the sametechnology there you know
(48:22):
technology there.
The
Dr. Steven Toenjes (48:23):
.
That is a very unique uhmedication.
Its name is trade name israyval.
It's the way to think of Reyvow, which is not really.
It's a Eli Lilly drug, butthey're not really marketing it
much at all.
It's actually a really goodmedication.
It functions very much liketriptans, but it only binds to a
very specific serotonergicreceptor and it produces no
vasospasm whatsoever, so it'slike a triptan that does not
(48:45):
have the cardiovascular risk.
It does make people sleepy andthe FDA required a
recommendation that someone notdrive for eight hours after
taking the dose and I think thatEli Lilly said well, we're not
going to make that much money onit, so they don't market it and
you don't see commercials forReyvow very much, but it is an
extremely beneficial drug thatsometimes is the solution to
(49:08):
somebody's migraine abortivetreatment.
Yeah, so one of the more commontreatments for chronic migraine
patients certainly is Botox,which the generic of Botox is
onabotulinum toxin A.
There are multiple botulinumtoxins.
(49:29):
Just Botox happens to beonabotulinum toxin A.
It is something.
That's a procedure, though, andyou see pictured the little
dummy head down at the bottom.
The little dots that you see onthat head are the location of
the injections for a migraineprotocol injection.
(49:50):
If you count them up, it's 31injection sites and has been FDA
approved for chronic migrainesince 2010.
And millions of people havebeen given this medication.
It's been around a long timedecades before it was, you know,
a long time before it was evenFDA approved for migraine and,
(50:11):
as mentioned, is one of our mosteffective preventive treatments
.
Dr. Carolyn Tran (50:15):
So each time one of your patients comes in,
are they getting an injection atevery single little red dot
there?
Dr. Steven Toenjes (50:21):
Yes, 31 shots
Dr. Carolyn Tran (50:22):
31 each time.
Dr. Steven Toenjes (50:26):
Yes, and every three months.
Dr. Carolyn Tran (50:28):
Every three months.
Dr. Steven Toenjes (50:28):
Yes, and if my scheduling is such that
they're going to be late by aweek, believe me, they are
complaining about it.
They're beating the door downto come and get their treatment
because after two, two and ahalf months it starts fading out
and they feel their migrainesyndrome coming back, and so
(50:49):
nobody misses their Botoxappointments.
Nobody likes getting 31 shotsin their head, and so the fact
that anybody comes back at allis a testament to the efficacy
of the medicine.
Dr. Carolyn Tran (51:01):
That is true
Dr. Steven Toenjes (51:02):
As a matter of fact, in private practice we
never even needed to confirmBotox appointments.
Nobody would miss their Botoxappointment.
Dr. Carolyn Tran (51:10):
Do they have amazing foreheads?
Dr. Steven Toenjes (51:13):
We're not doing that.
We don't do it for cosmeticpurposes.
There are a variety of othertherapies where this is not an
exhaustive review of migrainetreatments.
Down at the bottom there aredevice therapies,
neuromodulation devices that canbe effective.
(51:34):
A lot of people have heardabout the Cefaly device.
They're difficult to use in theUnited States, mainly because
we can't get insurance to coverany of this stuff, despite there
being efficacy and safe.
These are safe treatments.
But just because, even ifsomebody has literally been
through all medicines and isreally still struggling, there
(51:58):
are still other treatmentoptions that we really kind of
haven't talked too much about.
And the neuromodulation devicesare, I think you know, really
really beneficial.
And behavioral management youknow one of the most important
things.
I give a sheet on behavioralmodifications that can be
(52:19):
beneficial in migraine patients.
Every new patient that comes inis going to get a handout on
the kind of behaviors that theyneed to be paying attention to
and those kinds of changesthings like staying hydrated,
not abusing caffeine, sleepingenough hours in the day an
important one, keeping yourcircadian rhythm the same,
(52:41):
meaning going to bed and gettingup at the same time every day,
trying to get some exercisethese minor things can really
dramatically impact headachefrequency in a migraine patient.
Dr. Carolyn Tran (52:53):
Yeah, and you just touched on those.
I just want to have a questionfor you, Dr.
Toenjes.
In terms of Memantine, some ofyou may recognize this
medication.
We often use it for Alzheimer's.
Dr. Steven Toenjes (53:06):
Yes, it's FDA approved to improve
cognition in moderate to severeAlzheimer's disease.
That's its FDA approval.
But there's some pretty goodstudies on its efficacy in
migraine prevention and itsmechanism of action.
You would guess it may beeffective and actually,
(53:29):
historically and I know this maysound weird before we got rid
of the pregnancy class system Memantine medications, was
pregnancy class B, so it was amigraine preventive agent that,
at least theoretically, we wouldthink would be safe to use
during pregnancy.
I've never done that, but that'sactually the, it is actually
(53:51):
true.
So I would say the biofeedbackand relaxation training you know
these are along the lines ofsort of the behavioral
modifications that we mentioned.
Relaxation training actuallyhas some pretty strong data in
functioning as both abortive andmigraine prevention.
(54:14):
Yoga as an exercisespecifically seems to be pretty
special in terms of its benefitfor migraine patients.
I've always thought that it'snot just the exercise of yoga,
that it's beneficial.
Yoga includes some relaxation,and so I've always wondered if
(54:35):
that's the reason why, you know,adopting a yoga habit as long
as you're careful with your neckand migraine patients, you know
is a very, very good idea.
Dr. Carolyn Tran (54:45):
Is that the relaxation of the muscles that's
giving you the benefit?
Dr. Steven Toenjes (54:48):
Absolutely, and that's what biofeedback is.
We'll just talk briefly about.
Sometimes it's worthwhile forpatients to actually kind of
formally track exactly how oftenthey're having headaches.
I like the Migraine Buddy one,but there are a variety of
tracking apps.
You know a calendar is atracking app that works as well,
(55:13):
but sometimes it's eye-openingto see really how often
somebody's having headaches andhow often they're taking
medications, and those kind oftracking apps really do exist,
and so I guess in conclusionsyeah, so what I hope that people
(55:36):
can take from this is anunderstanding of really how
common migraine is one in fivefemales, one in 10 males.
It is an extremely disablingdisorder that we usually don't
go to our doctor and seekattention or ask for help, and
(55:57):
actually usually our doctor doesnot ask us if we have headache
problems.
And so increasing awareness ofthe people sitting in the room
and your family members that arearound you If you're aware of
someone who has a significantimpact in their life from a
(56:18):
headache disorder, your job nowis to educate them about the
fact that there really are a lotof treatments and even
treatments that we're stillstudying and that are on the
horizon.
Keep the thoughts about thedifferent therapeutic,
supportive and preventivestrategies separate and walk
(56:41):
away from this understandingthat there are actually a lot of
therapies that we have in ourtoolbox to help mitigate the
disabling brain disease that wecall migraine.
Announcer (56:53):
Thanks for joining the MedEvidence! podcast.
To learn more, head over toMedEvidence.
com.
Call migraine.
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