“For now, they (the new drugs) look fantastic. They shake the ground under our feet. They will change the way we treat migraine.” Dr. Stewart J. Tepper, a professor of neurology at Dartmouth College
In many ways, migraine is in the same basket as fibromyalgia (FM) and chronic fatigue syndrome (ME/CFS). The disease is common, mostly strikes women, is invisible, causes massive amounts of suffering and gets little support at the NIH. In fact, migraine, with its 2-3 million severe sufferers and 30 million plus occasional sufferers, gets considerably less funding per patient per year (from $1-10) than ME/CFS. This is despite the fact that migraine is considered one of the top ten causes of disability in the world.
Migraine sufferers may soon experience an explosion of new treatment options.
Migraine, fibromyalgia, ME/CFS, interstitial cystitis, IBS, and vulvodynia are some of the mostly women-dominated pain and fatigue causing diseases which cause massive suffering and are virtually ignored by the NIH. The results of a survey of migraine patients by the nonprofit Institute for Clinical and Economic Review could have just as easily been referring to ME/CFS or FM patients. It reported that migraine sufferers, “frequently reported feeling frustrated, depressed, defeated, isolated, or a burden to society”. Some patients expressed suicidal thoughts and many complained of “not being take seriously”.
Patients had typically “tried extensive lists of preventive and acute treatments (including drug and non-drug therapies and lifestyle changes).” When treatments did work, they either tended to stop working or the side effects were too much.
Migraine, which is notoriously hard to treat, was long thought to be psychological and has a long history of discrimination at the doctor’s office. Finding doctors willing or knowledgeable enough to treat it is difficult. Decades after being shown to be a physiological illness, migraine is still so misunderstood that two years ago the New York Times ran an article titled, “Women’s Emotions Do Not Cause Their Migraines“.
Yet migraine has had a real breakthrough in treatment. The FDA just approved the first drug, a monthly injectable called erenaumab, designed specifically for migraine, and several more of its ilk will probably be approved over the next few years.
How did the big disease with little funding make good? Migraine researchers may not be getting much money or respect, but decades ago they uncovered a specific pathway involving a peptide (a peptide is a short string of amino acids – smaller than a protein) called CGRP (calcitonin gene-related peptide) that seemed to play a role.
CGRP is a potent vasodilator which enhances pain signal transmission and affects blood vessel functioning. In migraine, sensory neurons in the trigeminal system release CGRP. The trigeminal nerve – the largest and most complex nerve in the head – regulates sensations to the head, neck, sinuses and jaw and controls chewing. Any activation of the neurons in this trigeminal vascular system – which originates in the brain stem – can cause CGRP release, vasodilation (blood vessel swelling) and mast cell degranulation (inflammation).
It’s this overactivation of the trigeminal vascular system that causes migraine sufferers to retreat to dark places with low stimuli during migraine attacks.
New Possibilities for Migraine Sufferers
The new drug is not a panacea. It won’t help everyone. The studies done to date in about 3,000 patients suggest it will reduce migraine attacks by more than 50% in about 50% of migraine sufferers. A third of chronic migraine sufferers will see reductions in migraine of about 75%. One good note – in contrast to current migraine drugs which most migraine sufferers discontinue within a year, side effects are minimal.
By the end of next year, migraine sufferers could quickly go from having no migraine-specific drugs to being awash in them. The drug just approved should be available as early as next week. Decisions on Eli Lilly’s galcanezumab and Teva’s fremanezumab are expected by the end of this year. Allergen (ubrogepant) and Biohaven (rimegepant) are expected to file for FDA approval next year. It’s possible that by the end of next year, five new drugs specifically designed to treat migraine may be on the market.
*Since this article was written three CGRP antagonists (erenaumab: (Aimovig) ; galcanezumab: Emgality; fremanezumab (Ajovy)) were approved in 2018 and two more (Allergen – ubrogepant; Biohaven – rimegepant) are expected to be submitted for FDA approval soon.
Why is migraine treatment moving forward so quickly? For one, migraine advocates made diagnostic clarity a chief goal in their search for treatments – something that has not happened in ME/CFS. That diagnostic clarity gives drugs companies a clear patient group to target. For another, a clear biological pathway was established which made so much sense that when one version of a CGRP antagonist bombed, drug companies simply readjusted and took another tack.
The Fibromyalgia / Chronic Fatigue Syndrome (ME/CFS) / Migraine Connection
Similar patterns of gray and white matter abnormalities and altered brain energetics in GWI, CFS, FM, and migraine suggest that common central mechanisms may contribute to the type of headaches and cognitive impairments perceived as ‘brain fog’. Baraniuk
Migraine, ME/CFS and FM may be more alike than we tend to think. Migraines are believed to be greatly underdiagnosed in ME/CFS and in the population at large. In one study, migraines were present in 64% of Gulf War Illness (GWI) and in an astonishing 82% of ME/CFS patients vs. 13% of the healthy controls. Over half of the ME/CFS participants (56%) also meet the criteria for fibromyalgia.
A large study (n=1700) found that no less than 56% of fibromyalgia patients met the criteria for migraine. The “penalty” for having both fibromyalgia and migraine was steep. Women with FM and migraines had significantly higher chances of also having been diagnosed with hypertension (p<.004), asthma (p<.01), irritable bowel syndrome (p<.02), depression (p<.0002), anxiety ( p<.001), PTSD (p<.005) and finally (and most of all) chronic fatigue syndrome (p<.0001).
Migraine, ME/CFS, FM and irritable bowel syndrome are among the eight pain conditions a 2015 NIH report proposed “share common underlying disease mechanisms”.
In migraine, ME/CFS and FM, exertion and exposure to stimuli often must be curtailed dramatically. Whether in the midst of an ME/CFS crash, fibro flare or migraine attack, hypersensitivity to lights, sounds and odors is common. Plus, the fatigue and cognitive problems often found in the days after a migraine look very much like ME/CFS/FM. Migraine and ME/CFS symptoms are often substantially reduced during pregnancy.
Brain blood flow problems appear to play a role in both migraine and chronic fatigue syndrome.
Baraniuk and Rayhan proposed a similar model to migraine may be happening in ME/CFS. They noted that the cortical spreading depression (CSD) found in migraine typically leaves in its wake a hypoxic environment (low blood oxygen levels) and an emphasis, not surprisingly, on anaerobic metabolism with a corresponding increase in lactate levels. CSD is usually a time-limited event, but Baraniuk and Rayhan propose that it’s become chronic in ME/CFS and contributes to the anxiety, fear, fatigue, pain, allodynia and cognitive problems in ME/CFS and similar disorders.
Whether a CGRP connection is present in FM and ME/CFS is unclear. Despite CGRP’s strong links to pain and stimuli sensitivity, only one study – in 1998 – has assessed CGRP levels in fibromyalgia. (That study found CGRP in FM patients’ cerebral spinal fluid.) CGRP levels in ME/CFS have not been assessed, but Donald Staines of Griffiths University has long championed the idea that vasoactive (blood vessel-affecting) neuropeptides such as CGRP may play a role in ME/CFS. The blood vessels CGRP affects occur all over the body.
Besides migraine, increased levels of CGRP have been found in temporomandibular joint disorder, cardiac failure, hypertension, and, interestingly enough, sepsis.
Missing Diagnosis and Treatment Options?
In Baraniuk’s 2011 study, only forty percent of migraine sufferers had been diagnosed, and only a third were being treated with drugs. That thirteen out of the fourteen ME/CFS patients with migraines reportedly were responding well to sumatriptan (Imitrex) suggested that many people with ME/CFS may be missing out on a valuable treatment option.
Given the similar central nervous system processes Baraniuk and Rayhan believe are behind ME/CFS, migraine, GWI and FM, they proposed anti-migraine drugs could be helpful in ME/CFS/FM patients who do not experience migraines.
The new drugs coming on the market are biologics which are probably going to very expensive (~$7,000/year). It’s not clear what will happen with insurance companies, but they may require that recipients have tried other migraine drugs first before they will pay for these new drugs.
Could you be experiencing migraine without knowing it? With powerful new drugs for migraine that possibly could affect ME/CFS/FM coming on the market, now might be a good time to find out.
Conclusion
We clearly need more research into the intersections between migraine, ME/CFS, FM and other diseases. If CGRP levels are increased in ME/CFS and FM, clinical trials of the new migraine drugs would obviously be a possibility.
Whether the new migraine drugs apply to ME/CFS and FM or not, the migraine drug saga indicates that even in a disease with low funding (migraine = $21 million/year – NIH), if a clear pathophysiological pathway is found, treatments can follow.
We often look at the decades of seemingly fruitless work done on multiple sclerosis with despair. How will ME/CFS and FM make out, when MS, with all its money, has made so little progress? But that comparison is faulty. Migraine, a sensitivity disorder often found in ME/CFS and FM patients is a much closer match to ME/CFS than multiple sclerosis is. Fibromyalgia, another common comorbidity, has three FDA-approved drugs while receiving pitiful research funding, and seemed to be on the brink of two more last year.
At the Montreal ME/CFS conference, Dr. Nancy Klimas noted that the $40 million the Department of Defense has been giving Gulf War Illness annually has resulted in 10 clinical trials currently underway. That suggests that in several diseases which have similarities to ME/CFS, even moderate levels of funding can have a significant impact.
Hi again Cort
I’ve got something of interest for you to research. A friend of ours this side of the pond, recently passed from m.e. I’ve provided a link with the information. I think it’s worth looking into ganglionitis as she was the second to have this in her brain.
http://www.meassociation.org.uk/2018/05/inquest-ruling-young-drama-student-merryn-crofts-killed-by-m-e-18-may-2018/
Thanks Steve. Really interesting Several hypotheses including Van Elzakker’s and Pridgen’s suggest infections or problems with the nerve ganglion could explain a lot. Getting the sensory and autonomic nerves tweaked makes perfect sense to me. It’s interesting that in migraine HSV sets up shop in the trigeminal nerve ganglion. Thanks for pointing that out. 🙂
I’ll keep you posted from our end. Seems like our biobank just got massive funding from the nih. Hopefully something comes from all this.
Thanks again.
So glad to hear that. If there’s a link or anything you can share please let me know. So glad to see the NIH spending some more money around and hopefully building collaborative Networks.
https://cureme.lshtm.ac.uk
Here you go 🙂
In theory then, this would help trigeminal neuralgia, correct?
I don’t know but I think it would be a possibility. It appears to be quieting that nerve down.
$2.1 million dollars – last October – biggest single biomedical investment in ME/CFS in Europe ever. I had no idea! Woo – woo – good for the NIH. That’s a nice chunk of change and hopefully will spur collaborative efforts.
Unfortunately with Brexit it’s also probably the last investment we’ll receive off anyone for awhile.
Silly voters! 🙂
I feel like crying for this young women who suffered so much. Why could she not just been hospitalised and treated. I know the answer, its because of the never ending stigma of ME/cfs. She would probebly got graded excercise and cognitive behavioral therapy. I feel so sad for her family to.
And why only now a brain donor center. I am a long time (3 decades) sufferer off this illnes (am now severelly ill myself)and I remember before the internet they did a few autopsies on 2 or 3 brains from ME/cfs sufferers. All these decades are lost. How many have died untill now. And why only the brain and not the whole body? When will our desease finally be respected and believed by every one?
And Cort, in your last post, you wrote that you would have it in the next blog about nancy klimas?
I was just talking to someone who works for Amgen. She is headed to a big company meeting and I asked her to inquire about use of their drug for fibromyalgia.
Nice! Please let us know what she says…
Cort, do you know if Nancy Klimas thinks that any of the drugs in trial for Gulf War Illness may be helpful for ME/CFS?
I’ve been wondering the same thing, but everyone’s been very tight-lipped about her current GWI study. I wonder how that’s going?
She reported that it has started. I’ll have something on that in the next blog on the Montreal conference.
I suffer chronic fatigue and chronic migraine also aching joints and irritable bowel since my early20s. Any progress in treatment would be most welcome.
What I am most interested out of all of this are the CGRP levels particularly in fibromyalgia but also in ME/CFS. If CGRP is causing increases in both pain and sensitivity to stimuli it seems like a natural for FM – and IF somebody looks at that – and they find high CGRP levels – then a clinical trial will hopefully be done and we could have another drug, hopefully a more effective one, for FM and perhaps for ME/CFS.
I have both chronic migraines and fibromyalgia and the CGRP blockers have been life changing! I haven’t had a migraine OR Fibro flare in 18 days, I feel clearer (less cognitive impairment/brain fog), more energy and I can do things I haven’t been able to do for YEARS, without triggering a migraine or Fibro flare. If people on this page have migraines, in addition to one of these other conditions, I would try the CGRP blockers. I do hope they do a study and test for CGRP in ME/CFS, like they did with Fibro. I hope these drugs are able to be covered off label and eventually approved in people with FM and ME/CFS!
Check out the 28 day Detox diet in Anthony William’s book Medical Medium. It is all organic fruits and vegetables (phytonutrients), and fights the viruses and heavy metal toxicities that cause ME/CFS and Migraines, and the Staph infection that causes IBS and gut issues.
He also recommends cutting out gluten, dairy, and eggs, since EBV thrives on these.
Then cut down on eating pork and vegetable oils (esp. canola oil), since the fats (and ‘slime’) clog the liver and circulation system. Up the Avacado & Omega3s to thin the blood and improve circulation.
Google ‘Medical Medium ____’ and insert CFS, EBV, IBS, Migraines, etc., to get free Soundcloud links to his weekly radio show for more info.
A lot of magnesium can also help CFS, the ATP energy cycle, and migraines. Start low, taking it a few times a day, and build up your tolerance level. Too much at once has a severe laxative effect, although that can help reset your gut biome!
It is all worth a try.
Interesting. Thanks, Cort. I’ve always had migraines, though after menopause, the severity lessened as well as how often they came. But the longer I have ME/CFS (disabled by it since 2002) the worse my sensory overload is, and the more migraines I get, although not always severe. The funny thing is, I am usually not too unhappy when one comes, because taking Excedrin (only a piece of one pill, I am so sensitive) helps a lot, and then the caffeine wakes up my brain enough that I can actually have a decent conversation with a family member, or read, or watch a video for a while. In other words, I am functioning much better on the Excedrin. If I take a little Excedrin when I DON’T have a migraine, it induces one, then Excedrin won’t help. (Sadly, caffeine in a drink will not give me the same benefit!)
I am too sensitive to handle one of the “big guns” drugs, I’m pretty sure.
Side note: Cort, due to bad sensory symptoms, I have trouble being online for very long. I can’t find a friend with enough time to keep track of info here. I just read the titles of your blogs, but miss info that could help me share with my doctor, potential treatments, etc. that are on the forums. Which would you say are the most important pieces to try to read, if we want to not miss important news that might be something new to try? Your site is our “doctor” these days. No one anymore in Phoenix.
Thanks again.
Isn’t that something! Excedrin gives you some mental energy but only during a migraine….and caffeine does not help outside of a migraine. What a tangled web this all is. I suspect someone has an idea why this is happening. I, too, am spectactularly sensitive to caffeine. Just a little bit sends me flying.
Yes, Cort’s site has A LOT of info! I have no idea how he writes so well and follows all the technical writings in medical research if Cort has CFS himself.
A good website for basic info on treating CFS, FM, (etc) is by Dr. Sarah Myhill,MD in the UK.
I also see that all the notable CFS doctors have their patients follow the late virologist Dr. Martin Lerner’s ‘Protocol’ of 5 supplements to boost ATP cellular energy production, on top of a high quality ‘Optimized’ daily vit/min. I found that it, plus taking Iodine (Iodoral 12.5mg) and Selenium (+200mcg) a day to help the thyroid and heart function (as per Dr. David Brownstein, MD) helped me a lot, although it took awhile. No more cold hands and feet, and my heart rate recovers from exertion (stairs,’flat’ bicycling over a small bridge) in 20 seconds instead of 20 minutes.
I assume everyone on this website is on some version of this supplement plan, though no one talks about it much.
I don’t know that they are. Thanks for mentioning Iodine. What are the five supplements…CoQ10 I’m sure is in there…
Thanks Susan. I myself had a knowledgeable doctor who followed Dr. Bell, and had me on all the usual supplements for ME/CFS, and occasional IV infusions, B-12 shots, etc. He retired after 9 years of seeing him. I continue his protocols. I have not improved in my functionality in any significant way, but rather continue to decline.
New info and protocols (which replace my old doctor, as no other specialist) has been found) require online, bright light,headaches etc. I know of Dr. Myhill and Dr. Lerner, and will see if they have anything new that I can try. Thanks for the reminder. It’s the Pridgen protocol and others, like Dr. Chia, Dr. Montoya etc, where patients have recovered at least by 50% that I want to know about. My daughter is on Pridgen’s drugs,(though Valprex instead of Famvir) through a much less informed dr re ME/CFS or Fibro. She has not improved at all, after 3 months.
It’s those of us who are more severe now, despite following so many valuable diet and supplement protocols as I have, who cannot be online often, whom I believe this community in Cort’s wonderfully helpful site don’t hear from. They would like to be. They are usually in bed, with shades drawn, ear muffs or earplugs inserted. Even when I am able to sit up and read or listen to something, my cognitive problems are usually such,that I cannot often comprehend enough to make sense and come up with some sort of conclusion. And I was a writer, voracious reader with a post graduate degree. Like many of you.
I need to find someone with time to do the research for me, and have yet to be successful. I’ll try again. Thanks for your encouragement. At least we are not alone. May our God have mercy and compassion on us all.
It’s interesting that you say migraine and CFS/M.E. get better during pregnancy because my dysautonomia started almost as soon as I got pregnant. There are quite a few stories of women who have pregnancy induced POTS so the “better during pregnancy” is definitely not universal. I know POTS and dysautonomia are not the same as CFS or migraine but they do have many overlapping symptoms.
Thanks for this informative site btw!
Yes, it’s true that some people with ME/CFS and migraine get better during pregnancy but certainly not everybody. Given the changes and the stresses that the body goes through during pregnancy I wouldn’t be surprised at all if some people got worse.
I agree – lots of overlapping symptoms. I really hope we will have more studies that look at these diseases together.
Yes in my experience I got worse the first trimester and then better again, then worse again postpartum when I was weening of breastfeeding.
where can I find the results from the NIH-UK longitudinal studie from the fitst phase that ended in 2017. Are they allready there yet?
I’m afraid I am way behind on this. I’m just learning about it now but will report on it
thank you cort!
I ask myself why is it all so mysterious what the NIH does? why are they not more open about it?
A. I don’t think they’re good at getting the word out. B. They’re very careful and C. I don’t think many people actually take the trouble to ask how the NIH works.
and cort, where there now no better ways then gene expression what I thought I have read about, was not so reliable?
Since our underlying genetics is 99.99% the same amongst all humans, changes in the’Gene expression’is from Epigenetics, and toxins (like mercury), unbalanced or inadequate nutrition, and viruses alter these expressions.
Unfortunately, most research dollars are currently being spent trying to find these genetic causes instead of the viral or nutritional ones. This is expected to change in the next 10 years.
There is no underlying ‘genetic’ cause for anything that happens long after you are born.
Bad Epigenetic Expressions (chronic disease, cancers) can be reversed by better nutrition and not contracting or not over-feeding the bad viruses, such as EBV (HHV-3), HHV-6, CMV, shingles, etc., which we all carry at least one or two of. Each also has dozens of strains (like the Flu), so vaccines are difficult. ‘Bad’ viruses excrete neurotoxins that cause inflammation of the brain, nerves, guts, organs, and/or skin, while ‘good’ cousins of those viruses provide us some immunity against them, which is the principle behind vaccines and a healthy immune system.
It is all fairly simple:
Eat ‘clean’, stay active, avoid toxins, and enjoy life.
If not done, it is reversing this [in our industrial age] that is the hard part!
Do you have to have a specific diagnosis in order to obtain this drug? Do you have to take it daily or only at onset of migraine? And do you know correct dosage?
Currently waiting to hear what NICE will do about this on The NHS, hopefully hear this month.
Interestingly when i take my migraine tablet, Almogran, my fibromyalgia symptoms go completely for 24 hours, sadly they return. But there’s a link between the two, isn’t there?
It appears there is!
I believe there is a link. I noticed this alleviation of my Fibro flare or pain when I took my triptan for a migraine and now I am taking one of the new CGRP blockers and haven’t had a migraine OR a Fibro flare in 18 days! It has been a miracle for me!
All patients Diagnosed with EDS3 Hypermobility suffer from Narcolepsy so this explains & some could also have diagnosed Silent Migraines or both &
a Chocolate Skin Allergy found by testing in Allergist’s Offices so consuming any Chocolate would be out even any forms of Caffeine in coffee
tea Sodas numerous items even Nuts, Peanuts should be stopped entirely strict diets used in (SM) Silent Migraines
Fibromyalgia pain can be frustrating. I had Fibromyalgia for at least 7 years. My initial symptoms were fatigue and lower back pain which were manageable, In 2015 it really kicked in with widespread pain, soreness, sleeplessness, inflammation and extreme fatigue. I tried so many medications and supplements to get some relief nothing worked, until last year, i learnt about FIBROMYALGIA SUCCESSFUL TREATMENT from Rich Herbs Foundation (RHF). I was skeptical it would help, but i gave the treatment a try. Few weeks into the treatment, I went back to work feeling good and my legs weren’t hurting, i almost forgot how long it has been since I felt this good and normal. The pain was 95 percent gone on my legs and lower back, the inflammation was gone too. Visit RHF we b page ww w. richherbsfoundation. c om. Here I am 11 months after the treatment and i still feel good and active.
I have both chronic and debilitating migraines and fibromyalgia (etc, etc). I had not been able to take any other preventative medications and only had a triptan as a rescue med (which usually worked, but I was so limited in how many I could take in a week). So, 18 days ago, I started Ajovy – one of the new CGRP blockers. I have not had a migraine OR a Fibro flare at all in 18 days ??! I know it does not work for everybody, but apparently, for some it is a miracle treatment and I cannot stress enough just how miraculous it has been for me! I couldn’t do anything without triggering the mechanisms for Fibro and migraines (cleaning, exercise, shopping ?, sitting in the wrong chair, walking in the wrong shoes, stress, lack of sleep, alcohol – you name it). I have done many of these things in the last 18 days and have still yet to trigger a migraine or a Fibro flare! I am hoping not to get any, but I realize that I may. I have a friend who also had debilitating migraines – 25 a month – who still has maybe 2 a month now and you can still take the triptans for those.
Anyway, I want to give people with Fibro, or even ME/CFS, hope that this might be another treatment option at some point. If you have chronic migraines, as well, I say try it ASAP, as long as you don’t have any contraindications.
I don’t know what the long term effects of this treatment will be, as it is so new, but I have no current side effects. I feel great! I even have a clearer head. It’s amazing how much brain fog is caused by inflammation and pain. It won’t work for everybody, but it is definitely worth a try!!
I was diagnosed with DRUG INDUCED LUPUS after taking Aimovig. My doctor believes Aimovig caused it.
If you are having Lupus symptoms (fatigue, hair loss, increased headaches, joint/muscle aches, fevers) ask your doctor to do an ANA blood test and a HISTONE IGG AB blood test. The Histone blood test is specific for drug induced Lupus.
Aimovig is not know to cause drug induced Lupus, but it has not been on the market long. My doctor said it will take time for a pattern to emerge. If you discover you have Drug Induced Lupus, please report it and share these blood tests with others as I believe most doctors will not think to look it.
If you do find you have Drug Induced Lupus, the good news is that it’s reversible … once you stop the drug, the Lupus will eventually go away.
I hope this is helps anyone having “weird” symptoms weeks/months after taking Aimovig.
I’ve been on Aimovig for almost a year now and it’s worked wonders for my migraines – unfortunately the fibro is well and truly still at large. I’ve had to cut back my hours working as a midwife in the last 6 months because the fibro flares have gotten worse… just when I finally felt like I could work more because the migraines were gone! So frustrating.
Glad to hear it’s helping others with their fibro even if I’ve lucked out! 🙂
Thanks for sharing your experience Carla. The search continues….good luck with it.