Migraine Management with Dr. Alex Melinyshyn

0:00 so I want to thank you Alex and also
0:02 Mike and Canada for inviting me tonight
0:03 to give you this chat about acute and
0:06 abortive treatment options
0:07 and so just as a quick overview for
0:09 those who are kind of new to the
0:10 migraine world we kind of think broadly
0:13 of medications for migraine and two main
0:15 Strokes you’ve either got preventive
0:17 options which are what you take every
0:18 day to try to Stave off a headache or
0:20 you’ve got acute or a board of lunch
0:22 which are the ones you might take as PRN
0:24 or on an as needed basis so we’re going
0:26 to focus on the as needed medicines and
0:28 everybody knows the common stuff but I
0:30 have some kind of unusual ones that I’ve
0:32 been collecting from my friends abroad
0:34 so it’s nice to just kind of get an idea
0:36 of some other ones you might be able to
0:37 try
0:40 so
0:43 I think it’s just Frozen so my name is
0:46 Alex melanishin I’m a neurologist and a
0:48 headache specialist and I run a headache
0:50 medicine practice in London Ontario so
0:52 I’d say about 95 of my uh practices
0:55 dedicated to headache with a little bit
0:56 of epilepsy brain tumors Ms that kind of
0:59 thing
0:59 um but I’m very interested about
1:01 migraine because it runs deeply in my
1:03 family and you know my other interests
1:05 within the headache World extend to
1:07 things like cluster headache psilocybin
1:09 and cannabinoid research so it’s a very
1:12 exciting time for for headache because
1:13 we have all these new treatments after
1:15 having Decades of relative quiet you
1:17 know on the on the medication front so
1:19 I’m happy to kind of share these new
1:21 updates with you
1:26 for disclosures just you’re aware I do
1:29 work with a lot of these drug companies
1:31 as they start to develop and analyze
1:33 their data and and kind of share it to
1:35 the market uh and so I’m often
1:38 participating in advisory boards for
1:40 companies like Novartis really Teva
1:42 linback and happy as well as like if
1:44 speaker uh talks to various groups
1:47 whether it’s pharmacists nurse
1:48 practitioners family doctors other
1:50 neurologists you know I try to spread
1:52 the gospel about migraine to make sure
1:53 as many of us are on the same page
1:56 trying to help other people with
1:57 headache
1:59 so for tonight what we’re going to talk
2:01 about is picking a migraine abortive
2:03 we’re also going to cover some of the
2:06 special considerations for groups of
2:07 people that traditionally don’t have a
2:09 lot of options this would be the elderly
2:11 you know technically people over 65
2:13 although for neurology I think 85 Plus
2:15 is ugly for me and the pregnant and
2:19 those who have cardiovascular risk
2:20 factors whether that’s you know vascular
2:22 disease and Gina hypertension
2:24 cholesterol diabetes when you have
2:27 enough of them we start to get a little
2:28 bit uh concerned about some of the
2:30 medicines
2:31 for acute treatments we’re going to
2:32 cover NSAIDs and tryptins I think most
2:35 people with migraine are familiar of the
2:36 two main categories we would consider
2:38 suvex and cambia are kind of new
2:42 versions of old friends that are
2:43 formulated in a much better way and may
2:45 provide you some extra benefit if you
2:47 haven’t had the chance to try them yet
2:50 one option that’s gaining a lot of
2:51 popularity especially South of the
2:53 Border is timel eye drops these are a
2:55 beta blocker eye drop that you can use
2:57 in an acute fashion and it’s a really
2:59 interesting option for those who fail to
3:01 respond to Conventional things or can’t
3:03 take those medications for whatever
3:05 reason
3:06 and then I want to introduce you to a
3:08 new class of medications called the G
3:10 pants if you’ve been going through the
3:11 migraine Canada Farms you’re probably
3:13 already familiar with them and their
3:15 imminent release here in Canada
3:17 um but they’re very interesting because
3:19 they’re similar to the cgrp antibodies
3:22 you may have heard about but depending
3:24 on which one it can be used as a
3:25 preventive or as an acute medication so
3:27 it’s really changing the way we think
3:29 about our medicines for migraine
3:32 another disclaimer here is that some of
3:34 the information included in this
3:35 presentation it references products
3:37 which are approved in the states under
3:39 FDA but have yet to be officially
3:41 approved by Health Canada so until we
3:44 get that official last seal you know we
3:45 have to warn you that the safety and
3:47 efficacy of these products is not
3:48 established and still being investigated
3:51 so if we’re coming across something
3:52 unusual like this mostly the gpants in
3:54 this case you’re going to see a little
3:55 Caution sign that I stuck in the corner
3:59 so I wanted to show you our Canadian
4:01 Headache Society guidelines for acute
4:03 treatment these are dating back a while
4:05 now 2013 which is like back when I
4:08 graduated from medical school so you
4:10 know they’re a little bit out of date
4:11 now and I know Suzanne Christie is
4:13 working very hard with her group in
4:15 Ottawa to update both the acute and
4:16 preventive guidelines
4:18 um so the problem is every time you turn
4:20 around we’ve got a couple new options
4:21 coming up so it’s constantly taking
4:24 updating
4:25 in this I just wanted to highlight some
4:27 of the more popular options that you can
4:30 consider I would say like we talked
4:32 about the Mainstays are two main
4:33 categories the NSAIDs and the triptans
4:37 of the trip dance I would say probably
4:39 the best bang for your buck from a money
4:41 perspective and efficacy is going to be
4:44 something like rhizotryption sumatriptan
4:46 or allatryptin and every doctor kind of
4:49 has their own Voodoo about how they
4:50 select them the triptans are a bit of a
4:52 rainbow you know there’s about seven of
4:54 them they all have slightly different
4:56 pharmacokinetics which means they may
4:57 take different amounts of time to peek
4:59 in your blood to absorb them uh to
5:02 linger in the blood for a while and some
5:04 of them can be taken as a pill orally as
5:07 a nasal spray or as a needle so
5:09 depending on which one you’re using they
5:10 have slightly different profiles
5:13 um the NSAIDs on the other hand I would
5:15 say the Mainstay of this one is naproxen
5:16 and it’s the cheap old medicine and it’s
5:19 cost effective it works very well
5:21 diclofenac is another cousin a
5:24 non-steroidal anti-inflammatory and this
5:26 one if it’s done in the right
5:27 preparation of the potassium salt in an
5:29 effervescent form is actually the
5:31 fastest you know instead of action and
5:33 and we’ll cover that in a second just to
5:35 be aware of the contraindications we’ll
5:36 go more into depth in these in the
5:38 future but for trip dance anybody who
5:41 had a history of coronary artery disease
5:42 stroke mini stroke heart attack angina
5:45 any kind of blood vessel disease
5:47 including raynauds uh you know you
5:49 really were contraindicated from taking
5:51 this they’re excluded from the trials
5:52 and because they constrict blood vessels
5:55 the thinking is like this might uh
5:57 produce you know vasoconstriction in a
5:59 ischemic event in people who are
6:01 vulnerable
6:02 um in pregnancy they’re considered
6:04 category C which is kind of like an
6:06 unknown kind of gray status but I’ll
6:09 give you some pearls later on that maybe
6:12 would suggest it’s probably safer to use
6:13 in this context
6:15 so
6:16 you might want to take a screenshot of
6:18 this one these are my favorite acute
6:19 medications and like I mentioned every
6:21 doctor kind of has their own bag of
6:22 tricks for NSAIDs I usually start with
6:24 the cheap stuff naproxen 500. you can
6:27 take it as a leave over the counter but
6:29 this is only 220 milligrams
6:31 I would say it can be safely used by
6:33 most people 500 milligrams up to twice a
6:35 day no more than 15 days per month and
6:38 that really is the upper limit of that
6:40 medication over your headache beyond
6:42 that you’re going to run the risk of
6:43 developing kind of a rebound or or
6:46 withdrawal type headache which we call
6:48 medication ovaries headache
6:50 for those people who say well you know I
6:52 really get terrible dyspepsia I can’t
6:54 handle advocacy
6:55 I tend to offer them their view matone
6:58 instead and this was a pearl given to me
7:00 by some of my mentors over at women’s
7:02 college and nabilitone is like the ugly
7:05 sister of the NSAID family for some
7:06 reason she didn’t get publicized well
7:09 and didn’t get a good shake from from
7:11 the advertisements it’s a lot slower to
7:14 Peak but it does linger longer in the
7:17 blood and it doesn’t cause as much
7:18 gastric irritation so I’ve had really
7:20 good success with those patients who
7:21 tend to be very sensitive in the stomach
7:23 so you can ask your doctor for that if
7:25 that seems to be the case for you
7:28 the one I’d like to highlight today is
7:30 tambia which you may have tried it comes
7:33 in a little white uh paper metal fashion
7:35 and you mix it into two ounces of water
7:38 and Stir It Up it is the fastest onset
7:40 of action but because it’s about you
7:42 know 10 bucks or so per dose it can be
7:44 out of the reach for some
7:46 for the trip cans my favorite are
7:48 rhizotryptin which is somewhere in the
7:49 middle of that Spectrum we’re talking
7:50 about and for those who find it isn’t
7:53 strong enough I tend to work it in a
7:54 stepwise fashion we’ll jump up to
7:56 sumatriptan which is the eldest and
7:58 sometimes the strongest but you know the
8:00 balance of that is it may have a little
8:01 bit more side effects chest tightness
8:03 tingling a bit of drowsiness
8:05 for those who find rides are tripped and
8:07 too strong I’ll drop down to things like
8:09 Elmo or Nara tripton which are ones that
8:11 we often use in children and tend to be
8:13 even better tolerated
8:15 the other Pearl that I think you know we
8:17 always tell people treat early
8:19 um but I think some patients
8:21 misinterpret this that if the headache
8:23 is already Brewing it’s too late and I
8:25 shouldn’t even bother taking my tripping
8:26 that’s not true tryptans are useful at
8:29 any stage of the migraine but the chance
8:31 of it working and nipping it in about
8:32 100 very quickly kind of falls off and
8:35 the best chance to treat it is either
8:37 during the aura or very early on in the
8:38 outset so treat early is the first Pearl
8:41 the second one is combining the NSAID
8:44 and the trip stem
8:45 and so there are certain formulations
8:47 you can buy like suvex where this has
8:49 already done for you or you can actually
8:51 take the separate prescriptions and put
8:52 them together
8:53 what I emphasize for my patients is that
8:56 the Gestalt or the sum of the parts is
8:59 greater than each individual and so one
9:02 plus one equals three kind of thing so
9:04 there’s a lot of synergy between these
9:06 medicines they help each other absorb
9:07 more rapidly and peak in the serum and
9:10 so taking it together understandably
9:12 many people want to take as little
9:13 medicine as possible but it should be
9:15 kept as a tool if you really aren’t
9:17 doing well with each agent alone
9:20 so don’t forget your acute medications
9:22 sometimes in a rush doctors just focus
9:25 on the prevention and if you suffer with
9:28 a migraine I would say if there are no
9:29 other contraindications to taking it you
9:32 should definitely try a trip tent it is
9:34 a specific medication for migraine and
9:36 if you’re on the fence then they say
9:38 probable migraine or maybe it’s a
9:39 migraine we don’t really know if it
9:41 responds well to a trip then that pretty
9:42 much clinches the diagnosis
9:45 contraindications include like I said
9:47 coronary artery disease which includes
9:49 Mi or you know angina a history of
9:52 stroke or mini strokes vascular disease
9:54 uncontrolled high blood pressure and
9:56 also Reynolds phenomenon this is another
9:59 thing that many people believe they have
10:01 Reynolds
10:02 when in fact they just have poor
10:03 circulation and we live in Canada and
10:05 they’re not wearing gloves so I will
10:07 actually sit down with patients and show
10:09 them all the pictures on Google
10:10 of Reynolds Phenomenon with the you know
10:12 digital power which is the areas of
10:14 white uh digits on the knuckles and
10:16 things like that uh the libido
10:18 reticularis and everything associated
10:19 with Reynolds and they’ll say well
10:22 actually no I don’t have that at all my
10:23 fingers just go a little bit pale and
10:25 cold and so I think that’s the
10:26 difference
10:27 if there’s any question at all and you
10:29 think you may have an inflammatory
10:30 tissue or autoimmune disorder and you
10:33 think you have Reynolds I would say it’s
10:35 worth a shot to go see the
10:36 rheumatologist and have them confirm it
10:37 for you
10:39 um you may need to try more than one
10:41 trip then before you find the one that
10:42 fits you and this is kind of unusual
10:45 because we think of the chemistry of
10:46 them as all being relatively similar and
10:48 comparable but that’s not the case
10:51 um you know they all have different
10:52 pharmacokinetics and sometimes it really
10:54 does take a trial of a few of them to
10:56 find one that that you tolerate very
10:58 well and that works very well for you
11:00 we talked about treating it early
11:02 the other point is that you can take a
11:04 second dose so some people don’t always
11:06 follow up quick enough sometime within
11:08 two to four hours if you’re not feeling
11:10 any better or you think you can do
11:11 better you can repeat a second dose both
11:14 of your trip 10 and of your handset
11:18 um the limits for the medication ovary
11:19 is headache I hammer home with my
11:20 patients every time we talk and meet
11:22 together they know I’m kind of clogging
11:24 a horse here uh that doesn’t require it
11:26 but it’s fewer than 15 days monthly for
11:28 the simple stuff and that’s you know
11:30 Advil Tylenol naproxen
11:32 um your your NSAIDs
11:34 for the harder things and this includes
11:36 categories like oh which personally I
11:40 avoided in my practice unless you’re
11:42 you’re palliative for a brain tumor or
11:44 really you can’t take any other medicine
11:46 uh tryptens butalbital containing
11:49 compounds which is like the ancient
11:50 Journal that we’re all trying to get
11:51 everybody off of these ones really have
11:54 to be used with caution the official
11:56 limit is 10 days per month but some
11:58 studies show that butalbital and opioid
12:00 containing compounds as little as three
12:02 to six days per month May toss them into
12:04 overuse headache
12:05 so let’s start with cambia
12:08 um like I mentioned this diclofenac
12:10 potassium it’s a fine powder you mix it
12:12 into you know two ounces of water which
12:15 is a really tiny amount and it’s kind of
12:17 nice because you can knock it back
12:18 quickly and it’s not everybody’s
12:19 favorite flavor uh it’s a combination of
12:22 mint and anise to mask the bitterness of
12:24 the medicine
12:25 um and you know so some people love it
12:27 other people not so much and uh the good
12:31 news is that it is very effective as an
12:32 abortive and so it Peaks within the
12:35 blood within 15 minutes and has very
12:37 rapid absorption doesn’t seem to matter
12:39 uh whether you take it with food or not
12:42 and I want to show you a graph here to
12:44 compare the diclofenac tablet the exact
12:47 same medicine and sometimes the
12:49 pharmacist will say oh don’t worry a
12:51 cheap version is you can get a tablet
12:52 and grind it up and and mix it with
12:54 water and it does the same thing that is
12:56 not true it is not a potassium salt and
12:59 so the potassium and sodium cells are
13:00 absorbed differentially and also this is
13:03 a special effervescent preparation that
13:05 facilitates that absorption so I would
13:08 caution that it really is not the same
13:09 thing and that really can be on this
13:12 instance is superior
13:13 so we get measurable plasma levels in
13:15 five minutes Peak plasma levels in 15
13:18 minutes food does not absorb the time to
13:21 maximum serum levels and just to show
13:25 you kind of the relative comparison to
13:26 the cousins can be as peaking there
13:29 somewhere around 15 minutes while your
13:31 other NSAIDs like ibuprofen and naproxen
13:33 are taking uh you know an hour and
13:35 Beyond to get up to those levels
13:39 for a comparison between cambia and the
13:41 dense things like sumatriptan
13:43 subcutaneous the SC this one is going
13:45 directly by needle under your skin but
13:47 as you can imagine not many patients
13:49 want to go that route every time they
13:51 have a migraine uh you know there’s a
13:54 significant delay between the the time
13:56 to T-Max which is the peak levels in
13:58 your blood so really cambia represents
14:00 an option to treat early those headaches
14:03 where you wake up with them from sleep
14:04 or they’re really fast onset or you just
14:06 need immediately
14:08 so uh these are kind of the the
14:11 indications which would be fast acting
14:13 attacks president Awakening or if you
14:15 have early nausea photosensitivity or a
14:18 thing for that
14:20 so there was a impact study which was
14:22 kind of their pivotal trial they
14:24 included adult patients with a history
14:26 of migraine weight or without Aura and
14:28 they only really excluded those who are
14:30 unable to perform the whole protocol or
14:32 were completely debilitated during their
14:34 heads which would render them unable to
14:36 actually prepare The Gambia
14:38 um so they treated one moderate or
14:40 severe attack and then 807 uh points
14:43 were captured in this and their primary
14:45 endpoint was to look at the number or
14:46 percentage of people at two hours if
14:48 you’re saying you know I’ve got no pain
14:49 no nausea no photophobia
14:51 so at two hours uh pain Freedom happened
14:54 in roughly a quarter of patients
14:56 compared to 10 with placebo
14:59 just to give you a relative uh you know
15:01 you can’t really compare apples to
15:03 oranges but in a similar meta-analysis
15:05 of trypten uh you know perhaps they were
15:08 paying free at two hours 29
15:12 for nausea light and Sound Sensitivity
15:14 looking at the freedom of this at two
15:16 hours cambia showed significant
15:18 statistical and clinical improvements
15:20 compared to placebo
15:23 looking at the Adverse Events that they
15:25 encountered in this trial
15:27 um you know there were not a lot of
15:29 significant divergences from Placebo
15:31 maybe a little bit of extra vomiting or
15:34 nausea and apart from that like it
15:37 wasn’t really a well tolerated or poorly
15:40 tolerated from a dyspepsia perspective
15:42 which is what sometimes you’ll hear
15:43 people say that it causes some stomach
15:45 irritation
15:46 so from the Canadian Headache Society it
15:49 recommends cambia offers a rapid onset
15:51 of action as early as 15 minutes and
15:54 that it should be considered as the
15:55 First Choice prescription for the acute
15:57 treatment of migraine attacks of all
15:58 severities the main issue here is the
16:00 cost because sometimes it is difficult
16:02 uh to get it covered and it may be eight
16:05 to ten dollars per dose
16:07 sometimes even with a good answer like
16:10 Gambia it just isn’t enough to treat
16:11 your migraines and you need to use more
16:13 than one mechanism
16:15 so that’s where Steve X comes in we had
16:18 already talked a little bit earlier
16:19 about combining your medicines and so
16:22 this formulation contains both
16:23 sumatriptan and naproxen but it’s not uh
16:27 the traditional signature than you think
16:28 it’s an RT formulation uh and so it’s
16:31 also co-absorbed with naproxen in such a
16:33 way that they needed to reduce the
16:36 milligrams of it you don’t need the full
16:38 100. so it’s indicated for the acute
16:41 treatment of migraine with or without
16:42 Aura recommended dose is to have one
16:44 tablet and you can repeat it uh two to
16:47 four hours later if you still need to
16:49 maximum for two tabs per day
16:52 so it acts on multiple mechanisms in
16:55 migraine and I think that’s why it’s
16:56 more successful than either agent alone
16:57 so the trip down it prevents or reverses
17:00 the vasodilation which we think of more
17:03 as an epiphenomenon of migraine and not
17:05 the cause of the pain itself it inhibits
17:07 the release of cgrp and other
17:09 inflammatory soup that comes out of the
17:11 trigeminal vascular system during the
17:13 migraine attack
17:14 and it also helps to prevent Central
17:16 sensitization and inhibits the way that
17:19 we process and transmit pain in the
17:20 brainstorm
17:21 and naproxen on the other hand IT
17:23 addresses a peripheral mechanisms of
17:25 nervous sensitization uh by you know
17:28 inhibiting uh prostaglandinophen system
17:30 and creating an anti-inflammatory effect
17:32 it also prevents uh Central
17:34 sensitization and there’s evidence that
17:36 over time it may even reverse some of
17:38 that coming out of other pain literature
17:40 so it really is a unique uh formulation
17:44 because it disintegrates very quickly
17:45 and disperses and it’s able to kind of
17:48 get around the slowing of the gut that
17:50 occurs from migraine and that’s actually
17:52 we think the basis of the nausea that
17:53 many experience
17:56 so looking at some pivotal trials for
17:58 this one
17:59 there are actually two that they
18:01 repeated uh to be doubly sure and uh
18:04 they were primarily looking at pain
18:06 relief at two hours and so these were
18:09 placebo-controlled single attack studies
18:11 and uh so they were also allowed to take
18:14 rescue medication anytime two hours post
18:16 study drug uh just so that they weren’t
18:18 you know torturing them during this
18:20 trial but many did not need to so
18:23 compared to Placebo subox also achieved
18:25 significant decreases in light and Sound
18:27 Sensitivity and nausea two hours after
18:29 dosing
18:30 looking at the Adverse Events there were
18:33 no new safety findings for subex
18:35 compared to each individual component
18:37 alone so nothing new from this
18:39 formulation that makes you think it’s
18:40 more dangerous than either sumatrist or
18:43 an approximate loan
18:45 so in summary about Steve X It’s a
18:48 combination Superior to either medicine
18:49 given a loan if you put them together
18:51 the size of the effect is greater than
18:53 either agent and and that’s why I want
18:55 to hammer this home for you early
18:58 intervention results are improved for
18:59 both two hours and 2 to 24 hour
19:01 pain-free response onset of action about
19:04 30 minutes so a little slower than
19:05 cambia but still a good effect size and
19:08 it has reliable two-hour and sustained
19:10 pain-free response and so many people
19:13 did not need to take a second dose of
19:15 anything
19:16 most of those who are paying for two
19:18 hours remain pain-free at 24 hours so
19:20 for those of you who are concerned about
19:22 rebound you know like oh I’m gonna feel
19:23 fine tonight and I’m going to wake up
19:25 again with this migraine um you know
19:27 this medication tends to avoid that and
19:30 it may enhance patient compliance
19:31 because like I mentioned I mean I don’t
19:34 blame my patients most of them don’t
19:35 want to take extra medicine if they
19:37 don’t have to and so some may not feel
19:39 comfortable combining it even when you
19:41 know we give them reassurance
19:44 the next one I want to talk to you about
19:46 are the timel drops and this one is kind
19:48 of like an under the radar you know
19:50 those in the know kind of are gaining
19:52 traction uh with this idea so use
19:56 timelineate 0.5 percent and you put one
19:59 drop in each eye right at the onset of
20:02 migraine and then you can do it again 30
20:04 minutes later this came out of a really
20:06 fascinating observation it was an
20:08 ophthalmologist and his friend who also
20:10 treat migraines and they were talking
20:11 about helping their daughter and they
20:13 had observed some cases where in
20:14 treating glaucoma with these drops
20:16 patients reported a lot of improvement
20:18 in their migraines and then we get into
20:20 like well is this really a migraine or
20:22 is it a glaucoma attack who knows but uh
20:25 there’s a lot of good rationale why this
20:27 makes sense so oral timel the pill is
20:31 FDA approved for migraine prophylaxis
20:33 they’ve done the trials on it and it
20:34 works like Propranolol or metoprolol or
20:36 other ones from the same family
20:38 the issue with the oral is that it’s
20:40 kind of gradually absorbed through the
20:42 stomach like the other medicines and
20:43 first pass metabolism so when you drain
20:46 the whole bowel and stomach as it
20:48 absorbs food it all goes through the
20:50 liver first and you’re going to lose a
20:52 portion of that drug before it even gets
20:54 back to the circulation so you’re kind
20:56 of taking a little tax there
20:58 the ophthalmic drops on the other hand
21:00 it bypasses that directly into the
21:02 systemic circulation by being absorbed
21:04 through cornea and the blood vessels of
21:05 the eye so it also goes in through
21:07 lacrimal duct into the nasopharyngeal
21:09 mucosa into a lesser extent it’s
21:11 absorbed through the the conjunctival
21:13 epithelium around your eye and into the
21:16 GI tract from there
21:17 the maximum plasma concentration Peaks
21:20 within 10 to 15 minutes so very rapid
21:22 onset and what’s interesting is that one
21:24 drop of this results in a plasma
21:27 concentration of two nanograms per ml
21:29 within that time frame and it blocks
21:32 beta 1 and beta 2 receptors about 80
21:34 with that plasma concentration so
21:37 significant therapeutic serum amounts
21:40 can enter the bloodstream Through The
21:42 Eyes so this is a very interesting
21:44 finding
21:46 so we have a randomized crossover
21:48 placebo-controlled pilot study they were
21:51 looking at timelo eyedrop there’s no
21:52 Board of treatment for migraine and
21:54 participants were recruited out of
21:55 Kansas City neurology and Ophthalmology
21:57 clinics they also posted some flyers
21:59 around the Hospitals and Clinics they
22:01 included any men or women over 18 who
22:03 had a good diagnosis of migraine by ic83
22:06 and then they gave them screening neuro
22:09 and eye exams
22:10 these people who passed the screening
22:12 were then randomized one to one to
22:14 either get uh timolol eye drops as we
22:17 mentioned with that dose or artificial
22:19 tears which are just saline and they
22:21 were doing one drop in both eyes stood
22:23 on that and 30 minutes after
22:25 the participants were followed for five
22:27 visits over four months so each a month
22:30 between each visit and crossed over at
22:32 the two-month Mark so at that point
22:34 they’re given a three-day washout period
22:35 where they take no drops and then they
22:37 switch over and they still don’t know
22:39 they’re blinded at this point
22:41 the participants rated their migraine
22:43 attacks on a scale of zero to three in
22:44 terms of severity and at the end of the
22:46 study they were asked to rate the
22:48 effectiveness of their drops on a scale
22:50 of one to four
22:53 so in the course of the study almost 200
22:57 separate migraine attacks were studied
22:59 among 10 different individuals and they
23:01 rated the effectiveness timilal as 2.4
23:04 as opposed to Placebo 1.4 four
23:07 participants with 10 mL found it highly
23:09 effective compared to Placebo and one
23:12 founded the other way they thought the
23:13 placebo was much more effective
23:15 uh the average percentage of headaches
23:17 with the severity of none or mile to two
23:19 hours timel was 78 versus placebo 57 and
23:23 you may be saying well look at the size
23:25 of these Placebo responses what I would
23:27 say is that pain is extremely
23:28 psychological and expectation really
23:30 does affect and if you look at any of
23:32 our trials in migraine or other pain
23:34 niches throughout the literature Placebo
23:37 response can be quite significant and so
23:39 I think sometimes people feel like
23:41 Placebo means fake or it’s not true but
23:43 it’s a very valid and useful therapeutic
23:47 tool and I think we have to respect the
23:49 size for us to prove that a drug is
23:52 useful you just have to prove that it is
23:53 in excess of the placebo
23:55 and I think uh we’re starting to see
23:58 some evidence here for timelo uh
24:00 although the quality of this trial is
24:01 limited by you know size and statistical
24:04 significance so they did some statistics
24:07 to determine the validity of this
24:08 finding and they uh wanted to account
24:11 for repeated measurements across them
24:13 the difference in this trial was not
24:14 found to be significant so we have these
24:17 cutoffs of p-values which determine
24:19 whether or not the probability of a
24:21 finding is attributed to chance alone
24:23 um and really the limitation of this is
24:26 the sample size if we can do a very
24:27 large perspective controlled trial of
24:29 this uh this may be able to demonstrate
24:32 the signal but I will tell you those who
24:34 use these drops think like they swear by
24:36 them and they seem to be quite useful
24:38 what’s nice is that you know when we’re
24:41 taking this approach we would say well
24:42 we got to balance the risks and the
24:43 benefits uh Adverse Events one person
24:47 had a branch retinal artery occlusion uh
24:49 which is a type of stroke in the back of
24:51 the eye and it was taking Placebo so
24:54 it’s really thought not to be related to
24:55 the trial
24:56 no real other Adverse Events including
24:59 low blood pressure or slow heart were
25:01 observed during the trial
25:04 so in summary you can use these 0.5
25:06 drops one drop in each eye at the onset
25:09 of migraine and 30 minutes later
25:10 generally well tolerated with few side
25:13 effects even with daily use
25:15 however they’re not tolerated by
25:17 everyone and this goes back to Alex’s
25:20 warning about talking to your family
25:22 doctor to see if it’s appropriate for
25:23 you
25:24 um some beta blockers can lower your
25:26 blood pressure slow the heart rate very
25:28 rarely they may have an adverse effect
25:30 on asthma or reactive airway disease and
25:33 in diabetics if you’re prone to
25:34 hypoglycemia the low blood sugar it can
25:37 mask the symptoms of this and they can
25:39 lead you to trouble so it’s important to
25:40 see with your Healthcare team if it’s
25:42 appropriate for you
25:44 next we’re going to jump to the
25:46 pregnancy World
25:48 um you know I think many women are
25:50 rightfully concerned about taking
25:51 medicines during conception pregnancy
25:54 and lactation it’s a scary time and
25:56 you’re making a really big investment in
25:58 bringing a new world a new life into the
26:00 world you want to give them the best
26:02 chance they have and for some women that
26:04 means they’re willing to sacrifice all
26:05 of their comfort and so I would say it
26:08 doesn’t have to be that way
26:10 you know the purists want to stop all
26:11 medicines except for their vitamins
26:14 um but I would say many things have
26:16 demonstrated significant safety and
26:18 tolerability for migraine uh treatment
26:20 paracetamol or Tylenol acetaminophen is
26:23 probably the safest medication
26:25 throughout pregnancy it’s considered
26:27 safe across all phases
26:29 well sumatriptan I would say most of us
26:33 feel that enough safety data has
26:34 accumulated through database research
26:36 looking at those who you know didn’t
26:38 know they were pregnant or were in such
26:40 Dire Straits that they took it anyway
26:42 and there doesn’t seem to be a
26:44 significant safety concern
26:46 other medications I just want to
26:48 highlight are NSAIDs they are generally
26:51 compatible with lactation breastfeeding
26:53 but really I would avoid them even
26:55 though they say okay yeah perhaps it
26:57 could be used very specifically in the
26:58 second trimester I generally advise all
27:01 women to stop NSAIDs during their
27:03 pregnancy it carries a small risk of
27:05 closing a little Channel across the
27:07 heart that the baby uses to breathe
27:09 while it’s in the amnion the fluid and
27:12 this is so important because if you fuse
27:14 it prematurely the baby will suffocate
27:17 and die in the womb so it is critical to
27:19 avoid these medications
27:22 so I came here
27:24 I would say first line treatments for
27:26 migraine are usually non-pharmacological
27:29 and this means working on your sleep
27:31 hygiene doing good light exercises
27:33 tolerated nutritious meals adequate
27:36 hydration and other formats that work
27:39 are you know biofeedback relaxation
27:41 training like deep breathing and body
27:42 scanning
27:44 the preferred acute treatment is when we
27:46 do have to use them would be things like
27:47 Tylenol gravel or diphenhydramine and
27:51 metaclopramide macro
27:53 Tylenol is really the safest option if
27:56 you want to just stick to the The Bare
27:58 Bones but sumatriptan is probably safe
28:00 during pregnancy based on our
28:01 accumulated data
28:03 Advil and other answers like I mentioned
28:05 are to be avoided
28:07 so let’s go quickly over the sumatriptan
28:10 nortriptanatrex pregnancy uh registry
28:12 Trek The Met is actually the American
28:14 name for suevex
28:16 and this was important uh to see
28:19 long-term safety surveillance data and
28:22 kind of give us our initial index of
28:24 safety and what I found was that no
28:27 evidence of turmotogenicity from
28:28 pre-clinical studies of sumotropin or
28:31 narrow trippin were reported so this was
28:32 the basis uh to to start this registry
28:35 and sumatriptan has been assigned
28:38 pregnancy category C
28:41 in this study uh this registry we had a
28:44 626 pregnancy outcomes obtained from 617
28:48 pregnancies so some of them obviously
28:50 had more than one child related and in
28:53 the first trimester there were 528
28:54 exposures
28:56 474 live-borne infants 34 spontaneous
28:59 losses 15 induced abortions five still
29:03 of births of the kids that were born
29:05 there were 20 birth defects uh in total
29:08 16 live born in for infants one
29:11 stillborn
29:12 and three induced abortions
29:14 so for an average of birth defect of
29:17 about 4.2 percent with a confidence
29:19 interval you know based on our
29:21 statistical analysis of 2.6 to 6.5
29:23 percent
29:24 uh in the second trimester there were 78
29:26 three infants of birth defects
29:29 uh and in the third trimester oh dear
29:33 kind of went out of order here but what
29:35 I wanted to show you here is that uh
29:37 birth defects of any trimester of
29:38 exposure are about 4.2 percent on
29:40 average and if you compare this uh with
29:43 the general population we have good
29:44 estimates of this and we think that in
29:47 the United States in particular uh about
29:50 one in every 33 children or about three
29:53 percent uh is born with a birth defect
29:55 and this Falls well within the range of
29:57 that confidence interval and after a
29:59 thorough statistical analysis they did
30:01 not think that um any increased risk of
30:04 congenital defect was observed
30:06 however what I want to stress is that
30:08 observational databases like these are
30:10 insufficient to be conclusive and so
30:13 really with limited data on the second
30:15 and third trimesters it really is a
30:17 conversation that you have to have with
30:18 each person and really weigh the risks
30:21 and benefits and and what they’re
30:22 willing to accept so I would say it
30:24 should only be given during pregnancy
30:26 when the benefit outweighs arises
30:29 we also have a cohort study here looking
30:31 at pregnancy outcomes after tryptin use
30:34 and this is a prospective observational
30:36 cohort study
30:40 and uh what I wanted to highlight here
30:42 was actually sorry I think we lost uh or
30:44 cut off our thing here but basically it
30:47 said the same thing that no significant
30:49 safety risk in terms of abortion or uh
30:52 spontaneous fatal defects was observed
30:56 next we’re going to talk about the
30:57 cardiovascular risk factors
30:59 um just to recap that this is not an
31:02 exhaustive list by any means but I want
31:03 to list the most common
31:05 contraindications for why you would not
31:06 take these drugs uh for NSAIDs
31:09 especially if you’re on anticoagulants
31:10 like any of the warfarin or the newer
31:13 ones like Xarelto or the 10A Inhibitors
31:16 you’re going to want to avoid these
31:17 because they increase the risk of a
31:19 fatal bleeding event or a serious
31:21 bleeding event whether it’s into your
31:22 bowel or into your head or elsewhere
31:25 if you’ve had bariatric surgery where
31:27 they do like a ruin y Bypass or some
31:30 other type of procedure like that an
31:32 anastomosis you may be at risk for
31:34 significant complications if you
31:36 continue to take infants and so many
31:37 people are forbidden from that
31:39 other people include different types of
31:42 ulcerative or inflammatory disease
31:43 whether it’s peptic ulcers IBD like
31:45 Crohn’s or ulcerative colitis and also
31:48 significant kidney disease as NSAIDs of
31:50 prolonged use can cause kidney damage
31:52 for the trip dance we’ve already covered
31:54 it a couple times here but I’ll recap in
31:56 brief coronary artery disease stroke or
31:59 mini stroke vascular disease including
32:02 uncontrolled high blood pressure
32:03 Reynolds phenomenon and more and there’s
32:06 an unfortunate group of people that fall
32:08 in the Venn diagram of this and you know
32:11 for many of them they feel very
32:12 disheartened because they walk away from
32:14 the doctor and they’re saying well you
32:15 know what all I’ve got for you is
32:16 Tylenol so good luck to you and that I
32:20 think is the wrong message because
32:21 there’s so much more that you can offer
32:23 them
32:24 so what can be used well of course there
32:27 is Tylenol
32:28 um for many of them aspirin is an option
32:31 unless you’re on a blood thinner
32:33 lismetidan was a medicine that we were
32:35 really hoping to see in Canada and it’s
32:37 the cousin of the trip dance called the
32:39 guy 10 and this one acts on a slightly
32:42 different serotonin receptor thought Not
32:44 to cause vasoconstriction and it was
32:46 going to be safe for use in these
32:48 patients however at the last minute
32:50 Health Canada pulled approval because
32:52 they couldn’t agree on the labeling and
32:53 the manufacturer would Drew their
32:55 application
32:56 other options include non-invasive nerve
32:59 stimulators the cephaly and the gamma
33:01 core which I spoke about in a different
33:02 talk for migraine Canada and we’ll lead
33:04 you there uh into the comments below
33:07 and uh the issue with those is that you
33:10 cannot use if you have any other
33:11 implanted devices so you know that if
33:13 you have a pacemaker or something you’re
33:14 kind of forbidden from them
33:16 gpents which we’ll get to in a second or
33:19 a new class of acute medication that
33:21 perhaps don’t cause medication over his
33:22 headache and may be also safe to use in
33:25 those with cardiovascular risk and we
33:27 talked about timel eye drops which could
33:29 be good but also have to be used in
33:30 caution if you have significant cardiac
33:33 disease
33:35 next up are the elderly uh you know I
33:39 think there are many people who are
33:40 Little White Knuckles with the trip
33:41 dance because the original trials did
33:43 not include people over 65. uh and this
33:46 is a problem I mean most of these people
33:48 who have migraines a particular
33:49 population uh it continues on uh as they
33:53 go through life and so I would say for
33:55 elders what I counsel them is that
33:57 naproximate hydroxyzine are the most
33:59 commonly used for for individuals with
34:02 migraine retention and certain rescue
34:04 medicines that we normally consider for
34:06 migraine like triptans and the younger
34:08 have to be used with more caution
34:10 because over time you accrue more
34:11 vascular risk factors and there’s a
34:13 significant risk of of stroke or
34:15 coronary disease
34:17 like I mentioned there’s a lack of
34:18 robust data beyond the age of 65 but it
34:20 has accrued you know in the same way
34:22 that we got those pregnancy databases
34:25 what’s important to note is that as you
34:26 get older your arteries Harden you
34:28 develop Trace diabetes and hypertension
34:31 cholesterol all these things and the
34:33 risk of these events increases over time
34:35 so it’s important to not just write a
34:37 prescription for three years and walk
34:39 away every time you go see your family
34:40 doctor it’s prudent once a year to
34:42 review all over your masses
34:44 absent any significant risk factors you
34:47 know I’m usually pretty safe to to
34:50 prescribe these for elders I look in my
34:52 practice and I think okay well I have a
34:54 500 pound OB 33 year old who doesn’t
34:56 walk and smoke every day uh and then I
35:00 have you know an elder who runs for two
35:02 hours every day and is 92 but you know
35:04 it’s a bit of the fiddle I think I would
35:06 have more compunction about you know
35:09 prescribing a trip then for the first
35:10 individual as opposed to this elder so I
35:13 think we have to think less about
35:14 chronological age look at physiologic
35:17 age and then the whole clinical picture
35:20 so risk for ischemic stroke and coronary
35:24 heart disease associated with migraine
35:25 and migraine medication among older
35:27 adults this was an interesting study
35:29 analyzing over 35
35:31 000 Medicare beneficiaries through their
35:33 EMR
35:35 and what they did was they found about
35:37 22 000 who had no history of
35:39 cardiovascular disease and matched them
35:42 to age controls uh about 87 88 000 who
35:46 did not have migraine or cardiovascular
35:48 disease then they took a second arm and
35:51 they took about 16 000 with a history of
35:54 cardiovascular disease and migraine and
35:56 they matched them to uh 63 000 patients
35:59 without migraine but with cardiovascular
36:01 disease
36:02 so the patients with a history of
36:05 migraine taking a trip and had a lower
36:06 risk for
36:07 um you know coronary heart disease
36:09 events versus those without a history of
36:12 migraine so in fact it was perhaps
36:13 protective there was also no evidence of
36:16 a difference in the risk of ischemic
36:18 stroke compared to match controls so you
36:20 know really it seems like it was safe in
36:22 this group the events occurred of course
36:24 but when you compare it to a large
36:26 cohort of people of the same age
36:28 relatively matched for their history of
36:30 cardiac health uh there wasn’t an
36:32 increased signal
36:35 other devices that you could consider
36:37 and this goes back to that talk I gave
36:38 previously with migraine Canada would be
36:40 the gamma core or the cephaly these are
36:43 the two that are available in Canada and
36:44 then you don’t have time to go into
36:45 detail today but you can see it in our
36:47 other talk unfortunately the inora and
36:49 the neurodio are not available in Canada
36:51 at present and I don’t think there are
36:53 plans to do
36:56 so next up on our agenda is the gpans
37:00 so you know we’re joking amongst
37:02 ourselves like I don’t know how people
37:04 name these medicines I think somewhere
37:06 they’ve changed a poor intern in the
37:08 basement they’re throwing down Scrabble
37:09 tiles to the name is new metaphors so
37:12 what is a gpent it is a small molecule
37:15 calcitonin Gene related peptide receptor
37:17 antagonist so that’s a mouthful
37:19 basically if you’re familiar with the
37:21 monocle antibodies cgrp is a chemical
37:24 secreted from nerve endings that is
37:26 pro-inflammatory and it perpetuates that
37:28 vicious migraine cycle if you can block
37:31 it either the molecule or the keyhole
37:33 that it fits into the receptor you have
37:35 a good chance of reducing migraines so
37:38 this one is an oral as opposed to the
37:40 injected antibodies and when we think
37:43 about how cgrp plays a role in migraine
37:45 blocking it seems to block the
37:48 neurogenic inflammation it decreases the
37:50 dilatation of arteries and it inhibits
37:52 pain transmission I mean this is kind of
37:54 a simplistic overview but I think it’s a
37:56 really good place to start
37:58 so what is cgrp it’s a really large
38:01 neuropeptide and it is the most abundant
38:03 one in the trigeminal ganglion it’s
38:05 located in both CNA Delta nerve fibers
38:09 and it gets released with glutamate
38:11 whenever you activate that trigeminal
38:13 gangla the trigeminal ganglion and the
38:15 trigeminal cervical complex is the area
38:17 through the brain stem that we think not
38:20 generates the migraine perhaps but is
38:21 the main Highway through which we
38:23 transmit and process pain for migraines
38:25 and so it has a lot of different
38:28 functions all over the body but luckily
38:30 most of these are in parallel so it’s a
38:32 redundant molecule and blocking it
38:34 doesn’t seem to cause many side effects
38:35 except in migraine where it turns it off
38:39 so how did we start to think about this
38:42 as a potential Target even
38:44 um you know there was a couple really
38:46 smart people who made some interesting
38:48 observations about cgrp back in the 80s
38:51 and they noticed that levels in the
38:53 blood were raised during a migraine and
38:55 these dropped when you gave them
38:56 sumotriptan
38:58 in migrants when they were in that Pro
39:00 monetary phase where the headache is
39:01 coming on cgrp was up and compared to
39:04 when you look at just the intraectal
39:05 part where they have no headache
39:08 interestingly I don’t know how they got
39:10 ethics approval to do this they took
39:11 healthy controls with no migraine and
39:13 Infused large quantities of cgrp
39:15 intravenously and this was able to
39:17 Target you know a significant headache
39:21 we also noted that there’s increased
39:23 levels of cgrp in chronic migraines as
39:25 composed compared to episodic migrainers
39:28 and even higher than those controls who
39:31 had no headaches so it seems to be dose
39:32 dependent
39:33 also another researcher realized that oh
39:36 increased levels of cgrp predicts
39:38 response to Botox so all of this
39:40 evidence started occurring and people
39:41 thought well what happens if we block it
39:44 so here come the new cjrp antagonist
39:48 that you can take orally
39:49 poised to come to Canada hopefully soon
39:51 we’ll have a bro Japan somewhere between
39:53 November to January and then we will see
39:56 arrival of a togapentin or imagine that
39:58 and they’re all slightly different but I
39:59 highlighted a couple things here
40:01 I told Japan can be used as prevention
40:03 for both episodic and chronic migraines
40:06 ubro Japan is approved for acute
40:08 treatment and remember Japan can be used
40:11 for acute treatment or prevention of
40:12 episodic and chronic migraine so it’s
40:15 really kind of blurring the Paradigm
40:16 that we talked about those two broad
40:18 Strokes of treatment acute and
40:19 preventive they all are at receptor
40:22 antagonists they all are taken orally
40:25 and they’re manufactured by various
40:26 companies
40:29 most importantly they do not cause
40:31 vasoconstriction like the tryptins
40:33 there’s no contradictations for youth
40:35 with patients with vascular disease and
40:37 thankfully during the trials no one
40:39 observed any serous vascular events
40:41 also important to highlight is that
40:43 they’re not thought to contribute to
40:44 medication ovary’s headache so this is a
40:47 good option to give to patients who are
40:49 currently overusing their acute
40:50 strategies without blaming them
40:52 another option is that this is good for
40:55 the needle phobic the patients who
40:56 really don’t want to administer a needle
40:58 and the thought of that is just
40:59 terrifying to them
41:01 when should we be considering these for
41:03 use I think for me uh anyone 18 year
41:06 older with a confirmed migraine
41:08 diagnosis they have failed to respond to
41:10 either endsets or triptans or they are
41:13 contraindicated because of the various
41:15 medical conditions
41:17 uh for the sake of time today I’m just
41:19 going to present the data from these
41:21 molecules in aggregate
41:22 but you know it’s important to note you
41:24 can never really make head-to-head
41:25 comparisons of these trials uh just
41:27 because uh you know they’re all slightly
41:29 different in the way they design them
41:31 they measure the outcome and so it
41:33 really isn’t fair to put them all
41:34 together
41:36 uh quickly about Uber Japan it’s an
41:39 acute treatment you take 50 or 100
41:40 milligrams as needed and you can take a
41:43 second dose at least two hours later the
41:45 maximum dose for 24 hours is 200
41:47 milligrams and if you have hepatic or
41:49 renal impairment you’re going to want to
41:51 adjust the dose to 50 milligrams
41:54 it’s well tolerated with side effects
41:56 similar to Placebo the most common
41:58 effects were nausea and dizziness and if
42:01 you’re in the know about the research
42:02 for these molecules the very first one
42:04 that came up calcipam did have some
42:06 fatal fatal liver hepatoxicity and
42:08 elevations they tweak these molecules
42:11 and they are particularly safe and no
42:13 significant liver signal was seen in the
42:16 latest iterations
42:18 on the other hand is another medication
42:21 safety of the more than 18 doses in a
42:24 30-day period is not established and
42:26 this is interesting because you can take
42:29 it every other day as a preventive
42:31 okay and then you top it up as needed on
42:34 the days that you don’t take it so it’s
42:35 a little bit of a confusing algorithm
42:37 and they’re actually repeating the
42:39 trials looking at Daily doses to get rid
42:41 of that
42:43 um contraindications for this would just
42:44 be hypersensitivity like an allergy to a
42:46 medication which is the same for any
42:48 medicine and the safety profile was
42:50 comparable to all the other cgrp
42:52 antagonist trials
42:55 so looking at the data these are the
42:58 major pivotal trials for ubo Japan and
43:00 romanticipant from an acute perspective
43:01 they were all very very large and well
43:04 designed and they did this to obtain
43:06 good statistical significance which they
43:08 all met their endpoints
43:09 looking at two hour pain Freedom uh you
43:12 can see that the difference versus
43:13 placebo is is is uh I would say
43:16 clinically significant however when
43:19 you’re calculating the number needed to
43:20 treat this is the inverse of the
43:21 difference versus placebo therapeutic
43:23 gain
43:24 um you may need to treat you know
43:26 somewhere between 10 up to 13 instances
43:30 in order to get one good outcome and so
43:34 we’ll talk a little bit more about that
43:36 in a second for two hour most bothersome
43:39 symptom Freedom again there’s some gain
43:42 versus placebo that with the number
43:43 needed to treat ranging somewhere
43:45 between uh you know 8 to 12.
43:49 so how do they measure up to the trip
43:51 dance like is this drug worth your time
43:54 uh there is a comparison of the new
43:55 pharmacologic agent against the trip
43:57 dance a recent Gemma open network
44:00 paper and this included 64 randomized
44:02 controlled trials
44:04 and what it found was that the two-hour
44:06 brain Freedom triptans were Superior to
44:08 GPS with an odds ratio somewhere between
44:10 like 1.5 to 3.4
44:14 pain Freedom or pain relief at two hours
44:16 after the dose Lavita Dan ramangapan and
44:19 a brochure band were associated with
44:20 higher odd ratios of pain Freedom
44:22 compared to Placebo but lower compared
44:24 to tryptins and you can see the values
44:26 here on the left
44:28 comparisons between all the new agents
44:30 themselves were not really uh
44:31 significant
44:33 so you know maybe they aren’t as good as
44:35 tripped ends up front however the lack
44:38 of the cardiovascular risk through these
44:39 new classes may offer an alternative to
44:41 triptans for those who couldn’t take
44:42 them anyway
44:44 if we’re looking to compare uh the
44:47 numbers needed to treat this is a good
44:49 meta-analysis I looked at all the
44:50 triptans as well as the cost efficacy if
44:53 you want to delve deeper and you know so
44:55 maybe frobotripton is comparable to some
44:57 of these neurons it has a higher number
44:59 needed to treat whereas the other
45:02 triptans range somewhere between three
45:04 to four or even up to eight
45:09 so for overtryptin is actually like the
45:12 most costly and I think it has some role
45:15 for use in like perimenstrual
45:16 prophylaxis and things like that
45:18 um but I would say the bang for your
45:20 buck uh maybe looking at uh sumitriptan
45:23 rhizotryptin eletryptin
45:25 and uh
45:27 as a general rule of thumb I think when
45:30 you’re trying to understand the number
45:31 needed to treat like what it means to me
45:33 is that you would need like say the
45:36 number needed to treat is 20. that means
45:38 you would have to treat 20 instances
45:40 using this drug before you have one good
45:43 outcome that is not attributed to
45:44 Placebo or just the natural resolution
45:46 of a migraine so when you’re factoring
45:49 in cost I think you really have to take
45:51 it with a grain of salt and I would say
45:53 that you know a general rule of thumb is
45:55 a number needed to five
45:57 the FDA reviewed like the crude data
45:59 from these trials and calculated uh you
46:01 know these numbers needed to treat for
46:03 Freedom uh for Imagine band uh 75
46:06 milligrams 20 and for upro Japan
46:09 somewhere around 10 to 15.
46:13 the costs have yet to be determined in
46:15 Canada but they are pricey South of the
46:16 Border I mean the typical trend is that
46:18 we do pay much less for our medications
46:20 here but uh you know you can see that a
46:23 month supply is somewhere around a
46:25 thousand dollars American
46:27 um so we’ll have to see
46:29 um the cost of a single tablet of a
46:31 brand name trypton is somewhere between
46:32 13 and 18
46:34 um and then typically the wholesaler
46:36 generic versions are half to three
46:38 quarters cheaper
46:41 a quick shout out to Les mittidan we
46:43 mentioned earlier the the daitan That
46:45 Never Was and uh unfortunately we won’t
46:48 be getting it here in Canada but I
46:50 wanted to include it just because you
46:51 may hear about it through some of the
46:53 American channels it meant all of its
46:55 endpoints as well and the thought was
46:56 that it was safe in those with
46:57 cardiovascular issues and it didn’t
46:59 really have a lot of significant
47:01 cardiovascular Adverse Events just a bit
47:03 of disease
47:05 the problem with this one is that
47:07 because of the sedation or drowsiness
47:08 you’re advised not to drive your car for
47:09 eight hours after taking
47:13 so in summary NSAIDs and tryptins remain
47:15 the Mainstays of acute management
47:18 cambia it offers a faster acting
47:20 answered option
47:22 suvex improves adherence in combining
47:24 the agents and with its Gestalt effect
47:26 you know gives you a bit more efficacy
47:28 than you’d get from either alone
47:30 new migraine treatments have arrived to
47:32 Market and there are many more in the
47:33 works that are coming so I I think that
47:35 should give hope to many migrators
47:37 and the cgrp molecule antagonists are
47:39 effective safe and well tolerated a good
47:42 potential option for those who have
47:44 failed to respond to tryptins are insets
47:46 or are contraindicated for me questions
47:48 remain about the cost Effectiveness and
47:50 access in Canadian markets so with that
47:53 I want to thank you very much for your
47:54 attention and turn the table to some
47:56 questions