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Last updated on October 13th, 2020 at 05:08 pm

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Last updated on December 1st, 2020 at 04:40 pm

BOTOX (OnabotulinumtoxinA) FOR CHRONIC MIGRAINE; THE MOST EFFECTIVE PATTERN, TECHNIQUE, AND EVERYTHING YOU NEED TO KNOW. NOT ALL BOTOX TREATMENTS ARE CREATED EQUAL.

@Neuralgroover

Background

Botox (Onabotulinum Toxin A) has been a game changer for the treatment of chronic migraine. I’ve frequently seen it give people their life back (as they often tell me), restored their ability to function normally in all aspects of life, and pulled them from the dark rut of chronic migraine that people get stuck in as described here. It can assist in stopping medication overuse headache (rebound headache), which often accompanies and drives chronic migraine. Once Botox is working, patients can often wean off daily pills being used for migraine prevention. Botox is a neurotoxin made by the Clostridium botulinum bacteria. When ingested, it is the same toxin that causes botulism, a severe form of food poisoning. Yes, this concept freaks many patients out. However, the amount used for chronic migraine is a much lower potency and dose, and when used correctly, can be an amazingly helpful medication.

 

Botox is produced by Allergan (now an AbbVie company), and was FDA approved for the treatment of chronic migraine in October 2010 following this study. Since that time, it has technically remained the only FDA-approved treatment specifically indicated for the treatment of chronic migraine prevention. With that said, the array of standard preventive migraine treatments as well as the CGRP monoclonal antibodies are also commonly used for all spectrum of migraine from episodic migraine (14 or less headache days per month) to chronic migraine (15 or more headache days per month). Most insurances will generally require a failure of at least 2 categories of standard preventive medications before they will approve Botox coverage. With that said, 98% of commercial insurance plans cover Botox, and it’s actually fairly easy to get it approved through Medicare and Medicaid. In addition, Allergan provides a Botox Savings Program which will cover $1500 of any out of pocket costs per treatment and $4000 per year. So for most patients, Botox treatments can be covered 100% between this savings program and insurance coverage.

 

It is my hope that this blog can provide the education and guidance in optimizing Botox procedure precision and technique for medical providers to give the best results, as well as a great educational overview on Botox for patients so they have a better idea of how Botox works, the best pattern to get (which can be shared with their doctors), and what to expect in terms of how long it takes to work, suggested duration of use, side effects, and safety in pregnancy and breastfeeding.

 

How does Botox work for chronic migraine?

The primary and most important mechanism of how Botox works for chronic migraine is by disrupting the electrical communication signals of pain between nerves and ultimately stopping these signals from reaching the pain circuitry of the brain. Thus, it prevents the activation of pain and migraine networks in the brain. Botox does this by entering the nerve endings and cleaving a specific protein called SNAP25. The inactivation of this protein leads to the inhibition (stopping) of neurotransmitter and neuropeptide release from the nerve endings and the prevention of the electrical pain signals from firing off. It also causes temporary (3 months) paralysis of the muscle being innervated by those nerve endings. Thus, it also causes the muscles to chemically relax (by chemically paralyzing them). For example, this muscle relaxation is why Botox works for facial wrinkles. It causes the thin muscular layers to relax to where they can’t contract (and wrinkle the skin), and wrinkles go away. Interestingly, one of the early clues that led to Botox being studied for migraine treatment was that women who were getting Botox were also noticing that they would have much less migraine headaches. This eventually led to further trials looking at Botox treatment to prevent migraine.

 

How long does it take for Botox to work, how long should Botox be used for chronic migraine, and how effective is Botox?

Botox typically starts to kick in within 1-2 weeks, but many times patients say they feel it working within a day or so after they have been getting it for a while. Botox lasts about 3 months. Patients commonly notice some gradually increasing migraines 1-2 weeks or so before getting to the 3-month wear-off window. I have quite a few patients that can actually get a good 4 months out of a treatment, but that is not common. If patients consistently start to come in for their 3-month Botox appointment and migraines are not starting to increase significantly as it is wearing off, I will often try to extend the next treatment to 4 months. If they are still doing well at that time, I suggest that we try stopping it to see if the migraines have entered and sustained into a more infrequent episodic pattern. It can always be restarted if needed in the future. It should be avoided from repeating much earlier than 3 months because early dosing before the prior dose has worn off can lead to cumulative medication and subsequent side effects. This can also increase the risk of antibody formation against Botox which can make it less effective over time.

 

It is recommended to give the Botox a minimum of 2 rounds 3 months apart to get a good sense of how much benefit one can likely expect. The reason for this is that in the trials after the 2nd round, there was continued upwards improvement. With that said, I typically expect (and usually see) good improvement with the 1st round. Some doctors advocate for giving a full year (4 rounds separated by 3-month intervals) to see the full effect. However, I typically tell patients if they have gotten absolutely no benefit after the 2nd round that we should move on to another treatment option. On average, Botox decreased chronic migraine days by 8-9 days per month, as opposed to placebo which was 6-7 days per month.

 

What are the Botox side effects?

A great thing about Botox is that it is so well tolerated with much lower side effect risks compared to many of the medications used for migraine prevention. I’ve done thousands of Botox treatments and have never seen someone have a bad reaction or an allergic response. In general, I tell patients there may be some tenderness in the injection sites temporarily. It is a very tiny needle injected just under the skin in a specific standardized dosing pattern and takes only a few minutes. Infrequently, patients can have a temporary flu-like muscle achiness for a day or so after the Botox. If the Botox spreads into some of the muscles in the forehead, I always mention that there is a risk of eye lid droopiness (ptosis), although I have not seen this occur. A more extensive list of potential side effect risks (which are extremely rare and I’ve not seen), can be read on the Botox for chronic migraine Allergan website. Caution is also advised if Botox is mixed with bupivacaine or other “caine” medications as this can be a fairly common allergy of some patients to these medications.

 

Is Botox safe in breastfeeding and pregnancy?

Historically, Botox has generally been avoided and saved as a last resort option in these scenarios, and often still is. The longstanding concern for using Botox during breastfeeding is based in theoretical concern that the Botox could seep into the breastmilk and effect the baby, although this really hasn’t been reported. It has been shown that Botox is not detectable in the blood after intramuscular use, so excretion into breast milk is considered unlikely. In fact, there was a reported case of a lactating woman who had foodborne botulism. However, when the breastmilk and infant were analyzed, neither showed any botulinum toxin at all, and the infant was safely breastfed. With this in mind, the doses of Botox used medically are much lower than those that cause botulism. Therefore, the amounts ingested by an infant, if any, are suspected to be small and not cause any adverse effects in breastfed infants. Regardless, for extra precaution, it is suggested to breastfeed before the Botox treatment, store some milk, and then wait a few hours after the treatment before breastfeeding again.

 

Similar to breastfeeding, there are no published studies on Botox use during pregnancy. So, it is still often avoided if possible and saved as a last resort option. However, since Botox is not detectable in the blood after intramuscular use it is not expected to affect fertility or pregnancy outcomes, and an Allergan safety database report has remained consistent with this conclusion. Botox is designated as a US Food and Drug Administration (FDA) pregnancy category C medicine, meaning that there are no well controlled studies in pregnant women, so it should only be used during pregnancy if the benefits outweigh the potential risks. The good thing is that the majority of women naturally get significant migraine improvement during pregnancy (especially 2nd and 3rd trimester) and it is not uncommon to hear migraines go away during pregnancy. So many times preventive therapy may not even be necessary.

 

What is the best way to do Botox for chronic migraine?

If you are going to get Botox, you need to make sure you are getting the optimal dose, pattern, and technique. A headache specialist will have the most refined technique and experience doing Botox injections, and should be sought out to ensure you are getting the best technique if one is available near you. If you cannot find a headache specialist near you, make sure whomever you get the Botox injections from does them very frequently with good reviews. Other doctors that may do Botox injections as alternatives if a headache specialist is not available include some neurologists, pain management doctors, and primary care doctors, as well as some physician assistants (PA) and nurse practitioners (NP). With knowledge of the precise pattern and technique as outlined below, and enough practice, anyone should be able to do Botox procedures proficiently in the office. It is an easy procedure and can provide dramatic improvement in chronic migraine pain and disability.

 

The pattern that should be used and modeled after is the PREEMPT protocol (Phase III REsearch Evaluating Migraine Prophylaxis Therapy), based off the trial that led to FDA approval for Botox in the prevention of chronic migraine. The pattern of injections described and illustrated below are of the PREEMPT protocol. However, sometimes I will tweak some of the injection sites depending on the patient’s pain pattern. For example, if their chronic migraine is 100% one sided, I may give additional on that side in the temporalis muscle and occipital regions, taken from the opposite side where they have no or minimal pain. If they have prominent occipital neuralgia, then I will give additional dosing over the occipital nerves. The PREEMPT protocol used 155-195 units of Botox. Botox vials come in 200 units (either two 100 unit vials or one 200 unit vial). For almost all patients, I use the full 200 units and spread the additional 5 between the trapezius muscles, or use it somewhere else where the pain is most common such as over an occipital nerve in the back of the head. I may use slightly less in patients that have no pain at all in many areas of the head or shoulders and have a very localized pain (such as just in one side of the forehead), are elderly, or young in late teens or early twenties and have not had it before. Regardless, many of the spots the patient may receive it in, they may not have much pain. However, there should still be some degree of symmetry for muscle weakness balance and to still hit potential areas of chronic migraine input that aren’t recognized as overly painful areas by the patient. I also prefer to gently and briefly rub in the Botox spots right after injection. This helps to distract the brain from the immediate injection pain, flattens the area so it doesn’t leave the Botox as a small lump, and helps to slightly spread the area of coverage for the Botox to work (hitting as many of those nerve fibers and neuromuscular junctions as possible with each injection.

 

The depth of injection isn’t supposed to be deep. So if the needle is hitting the bone, it is too deep and will be less effective. The target of the injections is just below the skin and into the top of the muscle. This is where the neuromuscular junction occurs (where the nerves that innervate and control the muscles enter the muscle). This is the main target of the Botox. I like to be strategic where the Botox goes. If your doctor or health care provider is just rapid firing it in (which is always more painful), hitting the bone, you have Botox running down your face, it is more painful than when you get it done with other providers, or you get eye-lid droopiness (ptosis), you should think about moving on to someone with a more refined technique. I see patients all the time that have been getting Botox with me and then they have to get a round sometimes with a different provider for some reason. They invariably say it doesn’t work as well, is significantly more painful, and afterwards they refuse to get Botox with anyone else besides me following that experience. There is validity in that. I’ve spoken to one of the main doctors/scientists involved with developing the original Botox pattern, technique, and dosing for chronic migraine and he agreed that technique and spreading the Botox around strategically and precisely will certainly lead to a better result as opposed to just quickly and less carefully “throwing the injections in”. In fact, they were originally thinking of adding more spots to further spread the Botox around to hit more nerve endings, but they settled on the current pattern to make it easier and less complex to do.

 

The Botox trials were done by mixing Botox in 0.9% normal saline (basically, sterile water). However, I will sometimes mix the Botox instead with a numbing medicine such as bupivacaine or ropivacaine. The Botox typically takes about 1-2 weeks to start kicking in. So the addition of a numbing medicine can provide some temporary relief as the Botox is slowly kicking in. Many times chronic migraine patients are significantly tender throughout their head to the point the hair can “hurt” and feel sore. This is called allodynia, or central sensitization, and is a common finding in chronic migraine. The additional numbing medicine can also provide some temporary relief throughout some of these sore areas. In most patients, they have tenderness over their occipital nerves in the back of the head (occipital neuralgia), and this can also provide some additional temporary relief over these nerves. Many chronic migraine patients also have tenderness throughout their shoulders, and many have associated fibromyalgia. This can also be helpful with some temporary relief through these muscles, and in a way is like getting trigger point injections at the same time.

 

So, let’s go over the treatment pattern that I have seen to be most useful. First, you will need to get the supplies together, of course. For doctors and health care providers who are here to learn how to do Botox or fine-tune their skills, a detailed video of what you need and how to draw up the Botox can be seen here. I won’t go through the detailed steps here in mixing and drawing the Botox up, but in short, you will need:

-Botox 200 units (100 unit vials x 2 are typically used, but single 200 unit vials available too)

-1 cc syringes x 4

-3 cc syringe x 1 (to draw up diluent and mix in Botox vial)

-30 gauge ½ inch needles x 4 (to place on end of 1 cc syringes prior to injections)

-18-22 gauge needle x 1 (to place on end of 3 cc syringe to draw up diluent and mix in Botox vial)

-0.9% normal saline vial x 1 (alternatively can consider 0.25% bupivacaine or similar)

-Alcohol pads

-Gauze pads

 

The Botox procedure: Face and frontal regions of head (frontalis and corrugator muscles)

For these injections, I prefer to have the patient lying supine on their back and I stand at the head of the exam table behind them. That way they don’t see the needle coming towards their face and all spots are easily accessed from the top and sides of the patient. These spots are pretty standard in all patients. The things to keep in mind are not doing the Botox too low in the forehead. This can cause ptosis, eyelid droop, and asymmetric eyebrow pointing (think Joker in Batman). I typically inject somewhere just below the hair line and in the very top edge portion of the frontalis muscles or just above it. The 1stfrontalis muscle injection is identified as drawing an imaginary line from mid-pupil up to the top of the frontalis muscle and injecting there. The 2nd is in a horizontal line about a half inch medial to the first injection on each side. The procerus is injected at approximately the middle of the brow right between the eyebrows. The corrugators are injected just lateral to each side of this central injection, about a half inch to each side. All injection sites are 5 units.

 

The Botox procedure: Side of head (temporalis muscles)

For these injections, I prefer to have the patient lying supine on their back and I stand at the head of the exam table behind them. That way they don’t see the needle coming towards their face and all spots are easily accessed from the sides of the patient. The way that I teach our headache fellows and other staff to do the temporalis muscles are to have the patient clench their jaw and feel for the temporalis muscle to contract. This is felt at the anterior point of the muscle just behind the hair line in the temple region. This is the 1st injection. From here, imagine a triangle with this 1st injection as the 1stpoint in the triangle. Then draw an imaginary triangle from here extending further back on the side of the head with the next 2 injection points above and below (see illustration) this 1st point. Then from here, imagine a square connected to the triangle. The next 2 injection points are horizontal and further back from the prior 2 injections points. All injection sites are 5 units.

 

The Botox procedure: Back of head (cervical paraspinal and occipitalis muscles)

For these injections, I prefer to have the patient sitting up on the exam table with their legs hanging over 1 side. I stand on the opposite side of the exam table behind them. The cervical paraspinal muscles are injected 1st on each side. The 1st cervical injection site is located by feeling the occipital protuberance (bump in the middle along the skull base), and going 2 fingerbreadths down and 1 over. This happens to be where the greater occipital nerve pierces through the musculature, and is also the first site of where occipital nerve blocks are done. The 2nd cervical injection site is located just superior and lateral to the 1st injection site.

 

Next come the 4 occipitalis muscle injections. These are done along the skull base and are evenly spaced out. The 1st site is just lateral to the occipital protuberance. The 2nd site is lateral to the 1st over the occipital groove (this is a palpable groove). This is where the occipital nerve travels, and is also the 2nd site where I normally do an occipital nerve block. The 3rd site is lateral to the 2nd site. The 4th site is lateral to the 3rd site and is located just posterior to the mastoid bone in another palpable groove. This also happens to be where the lesser occipital nerve travels, and is typically the 3rdspot I usually do for an occipital nerve block.

 

If the patient has prominent occipital neuralgia on one or both sides, instead of the standard 5 units over the occipital groove region (where the occipital nerves travel), I will inject 10 units at once and take that extra dose away from the shoulder or temporalis muscle regions (depending on where they typically have the least amount of pain and may not need it as much). Otherwise, all injection sites are normally 5 units. Notice that the PREEMPT protocol does not include Botox injections further down through the neck. The reason is because this can often increase headaches and can cause head drop to the point where some patients may need to wear a soft collar for 3 months. Therefore, this area should be avoided.

 

The Botox procedure: Shoulders (trapezius muscles)

For these injections, I prefer to have the patient sitting up on the exam table with their legs hanging over 1 side. I stand on the opposite side of the exam table behind them. Patients with chronic migraine most often have a lot of neck and shoulder pain. 70% of patients that get a migraine will get pain and tightness in these regions. So, if they are stuck in a smoldering cycle of chronic migraine and high frequency headaches, it would make sense that they would have a lot pain and tightness in these areas. Many patients also have concurrent fibromyalgia, so these injections can also be helpful, similar to trigger point injections. The 1st 3 injections are along the top ridge of the trapezius muscle. If you feel the superior medial corner of the scapula, there is invariably a tender point and knot here. This is the 4th injection site. The 5th site is in the middle of the trapezius muscle bulk. This is the end of the PREEMPT protocol dosing. However, the last 5 units that is left over I typically split between sides by giving 2.5 units somewhere in the trapezius region on each side where there may be a tender or trigger point, or I’ll just give it all on one side if they have more spasm or pain on one side compared to the other.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

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Last updated on November 24th, 2020 at 04:42 pm

STOP LETTING YOUR CHRONIC MIGRAINE AND CHRONIC PAIN DEFINE YOU AND YOUR BRAIN PLASTICITY.

@Neuralgroover

Background

I see the worst of the worst headache, migraine, chronic migraine, facial pain, fibromyalgia, and chronic pain from many states and countries. I see patients who have been debilitated by pain, patients whose pain has destroyed their family, marriage, work life, social life, and the ability to function normally. They are void of hope and have lost all self-esteem and confidence, replaced by depression and seclusion. They hide in the shadows of life. They come into the office with dark sunglasses, hoods up, appear detached, soft-spoken with little to say, and have fully committed themselves to the mindset that they will never get better. And they won’t because they don’t allow their brain to develop the plasticity to escape out of that mindset and behavior. We’ll talk about this concept and brain plasticity more later. I have seen patients who slide into this mindset commit suicide because they see no way out. These patients are rampant and come from all walks of life; professionals such as attorneys to blue collar workers to the jobless. It is an equal opportunity nightmare of chronic pain syndromes. These patients evolve from a once normal life and function to one of minimal to no ability to function normally in life, career, or relationships. I have seen plenty of people pull out of this described rut of a chronic pain lifestyle. It’s possible, but it takes work. Most importantly, it takes the step of convincing yourself that it is possible and will be done, and then readjusting your behaviors, mindset, and thought process accordingly. Give yourself no other option than improvement and realize that there is always hope for improvement. The placebo response in clinical trials involving pain patients (and similar in other subgroups) averages around 30%! That means on average, 30% of pain patients will develop significant improvement despite taking a placebo (fake) treatment. This happens because they convince themselves that they are using the new treatment, and thus they convince their mind that they are improving, and they do! Your mind is the most powerful weapon in your battle against your chronic pain, so learn to use it to your advantage.

 

Let me be clear that chronic pain is real, it is valid, it can be debilitating, it shouldn’t be ignored or overlooked, it can validly negatively impact all aspects of life which can be out of the control of the patient. I profoundly empathize with these patients. However, there is a lot that is in control of the patient which they often do not realize, and that is my purpose for this blog article. Specifically, they do not realize that they are creating a self-fulfilling prophecy of never improving in pain or function, directly related to their behavior and mindset. No, this discussion doesn’t apply to everyone and all cases, but I would say it does apply to the majority of patients.

 

Many of these patients create websites, blogs, and social media accounts dedicated and centered around their chronic pain experiences. Their chronic pain becomes their persona, and who they are. It redefines them. This can certainly be helpful to others to learn about similar pain experiences and to feel that they are not alone, and I think it is fantastic that other patients can have these outlets and sources to share their experiences. However, it can also become a dominating way of life which dissolves away any thought, hope or attempt at improving their pain and overall function. These patients get to a point where living any other way besides centered around their chronic pain would seem abnormal to them. They focus their life, their daily activities, their restrictions, their abilities, and their relationships around their chronic pain. It defines them and dictates their life. They are chained and restrained from this focus. This behavior begins to feed into itself and they continue down a path where there becomes no chance at improvement because they don’t allow their mindset or focus to see that as a valid option, and thus do not initiate behavioral changes to try to influence positive changes.

 

This phenomenon is also reflected in patients who have chronic daily headache, chronic pain, chronic neck pain and whiplash syndrome related to a motor vehicle accident, work related injury, or some other event where they were injured. If there is litigation (lawsuit) involved, it is well known as a clinical predictor that they will rarely improve, because of potential secondary gain (financial, disability, etc.) from their pain, which their subconscious maintains focus on. There have been studies supporting this correlation as well. This phenomenon is not seen in other countries which are not as litigious and ready to sue over anything. We used to have a large unique chronic pain rehabilitation program which was very effective and helpful to many patients. A large focus of this program was on behavioral changes to influence improvements in overall pain and functional abilities. However, patients were excluded from entry if they were involved in any ongoing lawsuit related to their pain, because these patients invariably never got better until the lawsuit was settled and done, and it would be much more beneficial and cost effective to them after legal issues were resolved. We would then admit them following the conclusion of their legal battles if they continued to have chronic pain issues. I have seen many patients reverse their course from that dark reclusive patient scenario described above with the right mindset and approach.

 

How does pain behavior influence brain plasticity and your chances of improvement?

Anatomically and physiologically, this reclusive and socially isolated behavior and mindset of telling yourself that it is impossible for pain to improve or that one cannot function and live a normal life with chronic pain becomes a self-fulfilling prophecy. DON’T LET THAT HAPPEN!! This is solidly based in scientific and biological evidence. Behavior influences cellular, molecular, and physiological changes in the body and brain. Studies have shown that behavior (such as pain limiting behavior, social avoidance, etc.) causes structural and circuitry changes in the brain, which can be lifelong. Social behavior can also cause changes in the brain, although this can be more reversible. These structural changes in the brain and the circuitry of the brain, influenced by behavioral changes (behavioral neuroscience) and mindset, are called brain plasticity. Essentially, plasticity refers to the nervous system’s ability to constantly modify its organization, structure, function, and circuitry connections in response to experiences, behavior, and an endless list of other influencing factors such as pain, stress, diet, emotion, medications, and many other things. Brain circuits related to chronic pain overlap with circuits involving anxiety, depression and some mood disorders. Mood disorders such as depression can affect the plasticity of chronic pain, and likewise chronic pain can influence plasticity of depression and other mood disorder circuitry.

 

Treatment and conclusions of chronic pain

Treatment is difficult, requires patience, and involves treatment trial and errors (if one treatment doesn’t work, another is tried). The single most important treatment involves you, your behavior in how you respond to your pain, your mindset, and attitude which all in turn influence your brain plasticity positively, and chances of improvement. Do not let your pain define who you are and what you are able to do. Expectations are important in that you should realize that (typically) there is no quick fix or “cure” (but if you stumble across one, which can happen, great!). Learning to live, deal, and function with the chronic pain is vital. If you realize this and make it a primary goal, it can in turn lead to improvements over time by modulating your brain plasticity and electrical circuitry. Most preventive treatments can take 2-3 months to see effects, and there is no way to expedite that. Hang in there and be patient.

 

Chronic migraine, fibromyalgia, and some other chronic pain syndromes often cluster together. The way to look at these types of chronic pain syndromes is that the neurological system is “hyperactive”, “overactive” or “hypersensitive”. So, the goal is to try to “turn down the volume” of this “hypersensitive” neurological system with medications or other types of treatments.  Never conclude that there is no possibility of improving. Remain active physically, socially, emotionally, and maintain active relationships. Treating depression or mood disorders is very important, and a good psychiatrist can make a big difference with this. Chronic migraine and chronic daily headache should have appropriate treatments which may include preventive treatments, CGRP mAb once monthly treatments, supplements and natural therapies, neuromodulation devices, eliminating rebound (medication overuse headache), and using appropriate abortive (as needed) therapy such as triptans, gepants and ditans. Most importantly, remain hopeful. There is always hope and there are constantly new types of treatments becoming available. You can do this!!!

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

 

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Last updated on November 24th, 2020 at 04:43 pm

CORONAVIRUS (COVID-19) HEADACHE AND TREATMENT, AND WHY YOUR MIGRAINES ARE WORSE WITHOUT EVEN BEING INFECTED.

@Neuralgroover

Background

Covid-19 headache, coronavirus headache, Covid headache and Covid19 headache are all terms for the same headaches which have been on the rise thanks to Coronavirus (Covid-19). This has been happening in patients who have gotten infected with Covid-19. We’ll be discussing that in much greater detail further down, as well as how to treat Covid-19 headache. Interestingly though, migraines and headache have been worsening in patients who have not been infected at all as well. So how is Covid-19 worsening headaches in patients who haven’t been infected? This phenomenon on worsening headaches related to Covid-19 in patients who haven’t been infected is predominantly occurring in patients with migraine. Let me tell you the reasons why.

 

Why are my migraines worse since Covid-19 and how are they treated?

We look at migraine as an electrical neurological event. It is no longer considered a “vascular headache”, which older terminology suggested. People with migraine have a hypersensitive, or hyperactive, neurological system. So when they encounter triggers, their migraine circuitry switch turns on easier, compared to someone without a migraine history. Basically, they have a lower threshold to trigger a migraine compared to someone without migraine.

Stress is a major, major migraine trigger, and one of the top triggers. Did I mention it is a MAJOR migraine trigger? Ok, you get the point. In addition to stress, there are a wide spectrum of triggers ranging from weather changes, hormones, foods, food additives, too little sleep, excess sleep, and a whole array of others. However, let’s talk about Covid-19 stress.

Unless you’ve been living in isolation in a doom’s day bunker deep in the remote countryside, the Covid-19 pandemic has been very stressful on everyone. So not surprisingly, migraine has also been much worse in general for patients with migraine given these increased stress levels. Everyone’s world has been turned upside down with Covid-19. Our routines and life as we’ve known it were abruptly changed. Parents suddenly became teachers at home, despite no knowledge or ability of knowing how to teach. Screen time skyrocketed (which is often a migraine trigger) from virtual teaching, virtual school, Zoom meetings, and a whole spectrum of other nightmarish virtual work meetings. The frequent crashing of these virtual platforms for many people is also very stress inducing, and likely led to some broken computer screens followed by unanticipated repair costs, and ok, you get the point here. People became socially isolated, which worsened mood for many people, and this often correlates with migraines worsening as well. Spouses and family members found themselves in quarantines and spending way more time together than they were used to or liked to, and that can also be stress inducing for many couples. Kids were home constantly, needing entertainment for their perpetual “I’m bored” complaints, basically just never letting parents get a break, and there were many reports of children actually turning into demons at home. Ok, maybe not, but I think you get the picture. The bottom line is that there have been many changes in our normal routines which were often very intrusive, disruptive, and stress inducing.

Treatment of the increased migraine frequency during Covid-19 (or any other time of increase) consists of typical management strategies. Conservative measures including well techniques, yoga, medication, diet, hydration, proper sleep and exercise certainly play a role. If frequency remains high, then preventive treatment should be considered for a few months until migraines improve. Having 4 or more migraines per month is a general guideline of when a preventive treatment is often considered. Preventive treatments include natural therapies, supplements and nutraceuticals, daily medications, CGRP monoclonal antibody therapy, and neuromodulatory devices.

 

What is Coronavirus (Covid-19) Headache?

First of all, the International Classification of Headache Disorders 3rd Edition (ICHD-3) accounts for Headache attributed to systemic viral infection, which is common with many nonspecific infections including viral infections such as the common cold or other upper respiratory viral infections. So headache is certainly not specific only to Coronavirus, but it is common with many common viral infections. These types of nonspecific headaches are diagnosed with the following criteria:

 

  1. Headache of any duration fulfilling criterion C
  2. Both of the following:
    1. systemic viral infection has been diagnosed
    2. no evidence of meningitic or encephalitic involvement
  3. Evidence of causation demonstrated by at least two of the following:
    1. headache has developed in temporal relation to onset of the systemic viral infection
    2. headache has significantly worsened in parallel with worsening of the systemic viral infection
    3. headache has significantly improved or resolved in parallel with improvement in or resolution of the systemic viral infection
    4. headache has either or both of the following characteristics: a) diffuse pain, b) moderate or severe intensity

4. Not better accounted for by another ICHD-3 diagnosis

 

Coronavirus (Covid-19) headache refers to headaches that have been triggered in direct relation to becoming infected with Covid-19, which is also associated with a variety of other symptoms and a positive Covid-19 test. First of all, if you already have migraine, you will generally be much more likely to have an increase in headaches since your internal electrical wiring already predisposes you to having headaches easier when the body is under any stress (emotional, physical, infection, stress, etc.), as discussed above. So if you get infected with Covid-19, you may have an increase in your baseline migraines for this reason, similar to what often happens with other types of infections (including the common cold). However, headache is a common (and often early) Covid-19 symptom in patients who do not have a migraine or headache either, similar to headaches which can be caused by many other types of infections as well.

The Covid-19 associated headache is often daily and commonly has migraine characteristics (throbbing, pounding, nausea, sensitivity to light and sound), or it can have tension type headache character (dull achy pressure throughout head), or a combination of both. One small study reported that Covid-19 associated headaches also had some unusual features, including new rapid onset unrelenting pain (including a thunderclap headache presentation), higher intensity, and association with anosmia/ageusia (loss of smell/taste), diarrhea, reduced appetite, and weight loss.

Coronavirus headache may also present with a story which fits well with New Daily Persistent Headache (NDPH). This is a headache that begins as a daily headache and persists as daily for more than 3 months, without any other known cause. Classically, patients with NDPH often will come into the office and tell you the specific date the headache began and that it has never gone away since. It may fluctuate in the severity levels, but it never fully goes away. It often has an overlapping mixture of migraine characteristics (throbbing, pounding, nausea, sensitivity to light and sound), and tension type headache characteristics (dull achy pressure throughout head). NDPH most often occurs without a clear reason. However, notably one of the most common associations if there is one is a nonspecific viral infection such as a cold or upper respiratory infection that precedes the headache. Covid-19 is simply another type of virus which can be associated with this form of headache.

 

How is Coronavirus (Covid-19) Headache treated?

Treatment of Covid-19 itself should follow current guidelines as directed by your regular doctor as well as the CDC (Centers for Disease Control) and WHO (World Health Organization) guidelines. Beyond this, treatment of Coronavirus headache revolves around symptomatic treatment. This basically means you are treating the symptoms rather than the virus itself, as is the case with the majority of viral infections (such as common cold viruses) besides treatable ones such as herpes simplex virus (HSV) and varicella zoster virus (VZV). If the headaches have migrainous features, they can be treated as migraine, tension-type headache, or NDPH with acute/abortive options, and preventive daily treatment options if the frequency of headaches remains high and is not improving.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

 

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Last updated on November 24th, 2020 at 04:43 pm

WHEN TO SEE A HEADACHE SPECIALIST AND HOW TO PREPARE TO GET THE MOST FROM THE APPOINTMENT.

@Neuralgroover

 

Background

I see patients in our headache center from all over the United States and from many other countries. Many patients travel hundreds of miles by car or airplane for these visits, due to the shortage of available headache specialists (about 570 in the US). Many patients are lucky enough to be relatively close to a headache specialist. Whichever scenario you fall into, you want to get the most out of your appointment with a headache specialist in order to get on a better path to less headache or facial pain burden.

 

When to see a headache specialist

So first of all, when should you see a headache specialist? First off, any type of headache, head pain, or facial pain, is reason enough to see a headache specialist. Basically, headache specialists specialize in any type of pain or discomfort involving anywhere in the head or face. They also commonly see patients that may have other neurological symptoms which may not necessarily be associated with headaches, but their doctor wants to rule out a migraine “equivalent” disorder. Some patients can have neurologic symptoms without headache (visual, sensory, speech, vertigo, weakness, nausea/vomiting, abdominal pain), which may actually reflect a painless migraine disorder, such as migraine aura without headache. I have compiled a list below of a few of my thoughts of when your headache or facial pain treatment journey signals that it is time to see a headache specialist.

 

Reasons to see a headache specialist:

-You have a headache, head pain, or facial pain.

-Your doctor tells you, “your headache is all in your head”.

-Your doctor tells you, “there’s nothing else I can do for you”.

-Your doctor says, “I don’t treat much headache, but…”.

-You continue to have frequent headaches despite trying several preventive medications.

-You just don’t feel like you are making any progress despite a couple office visits with your doctor or their NP or PA (or you never even get to see the doctor).

-You don’t feel like your doctor is listening to you or taking your symptoms seriously.

-The doctor spends only a few minutes in the visit, so you feel rushed and unable to discuss all of your concerns.

-Your doctor is googling your symptoms in the office.

-Your doctor recommends that you take opiates/opioids for migraine treatment.

-Your doctor says it is ok to use NSAIDs, OTCs or triptans more than 10 days per month or butalbital/fioricet/fiorinal more than 5 days per month on average for migraine treatment.

-Your doctor says your headache is “because you are depressed”.

-Your doctor does not give you a more specific classification or name for your diagnosis.

 

What information should you gather before the visit?

Unfortunately, we all know how strapped for time most physicians are during office visits due to a variety of factors such as low insurance reimbursement and the need to increase patient volume to compensate for this and break even. So to get the most out of your office visit, making it efficient and helpful, it is important to compile certain information in preparation. Typing out this information and bringing it to your office visit is a great idea. It is also a great idea to keep this as a running file that you can continue adding to in your personal files. This helps to eliminate time wasted in the office that could easily be organized and thought through prior to the visit, allowing more time for the important parts of the office visit; optimizing the diagnosis and treatment plans. Some of this information you may not have available, and that is certainly ok. You may be able to retrieve some of it from records, memory, and your local pharmacist.

Never assume that your local doctor’s office has faxed all of your records ahead of the visit. If that happens, great. However, many times patients are told that the records will be sent, but when we see the patient, we have no records that were sent. So, it is always best to bring all of your records yourself. Furthermore, it is good to have copies of all of your medical records, testing, etc. for your personal files anyway.

 

The following list are items that I have found to be the most useful for patients to have gathered and thought of prior to the visit, allowing the most efficient and useful office visit:

A) Acute/abortive headache or pain treatments (used “as needed”). This information is also needed in order to pursue insurance approvals for various types of treatments such as the newer gepants (Ubrelvy, Nurtec) or ditans (Reyvow).

-All that have been tried (which triptans, NSAIDs, neuromodulation devices, etc.)

-Doses used

-Responses (effectiveness, side effects) of each treatment

 

B) Preventive headache or pain treatments (used daily to lessen headache frequency/severity). This information is also needed in order to pursue insurance approvals for various treatments such as Botox or the CGRP mAb antagonists (Aimovig, Ajovy, Emgality, Vyepti).

-All that have been tried

-Maximum doses used

-Duration that each treatment was used

-Responses (effectiveness, side effects) of each treatment

 

C) Testing

-All CD and radiology reports for all brain MRIs, CTs, and other relevant testing for your headache or pain. Most CDs do not include the radiology report, and you need to request that separately. It is a good idea to have copies of all of these things for your personal files regardless. Bring them all to the office visit for the doctor to review.

-All bloodwork done in the past 5 years. Labs particularly important for headache evaluations include TSH, CBC, CMP, Vitamin D, Vitamin B12, ESR, CRP, ANA, to name a few, but this may vary and include more or less, depending on the specific clinical scenario.

 

D) Think about the clinical features of your headache or facial pain as listed below. These will be important questions that your headache specialist will ask. So, it is good to answer these questions in your head prior to the visit, so you can provide more accurate and thought out answers. This helps to prevent being put on the spot by questions you never really thought about which may result in forgetting some important details. For a free headache and facial pain self-diagnosis tool which incorporates all of these important questions that a headache specialist asks, look here.

-Location of the headache or facial pain

-Frequency of the headache or facial pain attacks

-Duration of the headache or facial pain attacks

-Description and characterization of the headache or facial pain attacks

-Neurological symptoms associated with the headache or facial pain (visual disturbances, numbness, tingling, weakness, speech disturbances, vertigo, etc.)

-Other associated symptoms with the headache or facial pain (nausea, sensitivity to light or sound, one sided autonomic features (runny eye, red eye, runny or congested nose, droopy or puffiness around eye))

 

Conclusions:

If you are able to gather all or much of the above listed information prior to your headache specialist appointment, you’ll be well on your way to a much more efficient and beneficial office visit. As a result, you and your doctor will be able spend more time in the office discussing the most important things rather than spending it trying to look up records or digging through your memory for various details. As a result, your doctor will have more time to better formulate a list of the most likely diagnoses, and best treatment approaches for minimizing the disruption of your headache or facial pain on your life. Good luck!!

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

 

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Last updated on November 24th, 2020 at 04:44 pm

AIMOVIG vs AJOVY vs EMGALITY vs VYEPTI. BATTLE OF THE CGRP MONOCLONAL ANTIBODY ANTAGONISTS; WHAT ARE THE DIFFERENCES AND WHICH IS BEST FOR YOU?

@Neuralgroover

Background

Aimovig vs. Ajovy, Aimovig vs. Emgality, Aimovig vs Vyepti, Ajovy vs. Emgality, Emgality vs. Vyepti, Ajovy vs. Vyepti. So many questions. so many answers. Let’s discuss them all. So it finally happened! The 1st migraine specific preventive medications FINALLY became available with the CGRP (calcitonin gene related peptide) monoclonal antibody (CGRP mAb) antagonists which first came to market in 2018. Prior to 2018, all of the migraine preventive medication options had been “adopted” from other specialties. For example, the 3 main categories of preventive medicines prior to 2018 were select evidence-based options within the anticonvulsant (antiseizure), antidepressant/antianxiety, and antihypertensive (blood pressure) medicine categories. These conventional migraine preventive treatments are certainly still used, can be very effective, and are discussed in much greater detail here. Migraine preventive therapies also include nutraceuticals and natural treatments, and neuromodulatory devices. This blog article will discuss and compare the 4 new options of CGRP mAb medications; Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab).

CGRP plays a strong role in neurogenic inflammation in the nervous system and is involved in the transmission of pain. It is also a potent vasodilator (dilates blood vessels), and increases overexcitability of neurons, both factors of which increase the intensity of migraine pain. CGRP has been studied since the early 1980s when it was discovered. It was found throughout the trigeminovascular system and trigeminal cranial nerves which transmit pain, so a role in migraine was suspected. The trigeminal nerves and their associated electrical circuitry throughout the brain, brainstem, and arteries in the brain is called the trigeminovascular system. This system is the basis and “on switch” for migraine. In the early 1990s it was shown that CGRP was released by the trigeminal nerves and levels increased during an acute migraine attack. In 2004, a CGRP antagonist (blocks the binding of CGRP to its receptor) was shown to abort an acute migraine attack, and decrease CGRP levels. Subsequent studies including preventive migraine studies done since 2014 with a CGRP antibody to block the effects of CGRP eventually led to 3 FDA approved CGRP mAbs in 2018, and a 4th CGRP mAb FDA approved in 2020.

 

How are the CGRP mAbs made and what is the science behind them?

The CGRP mAbs are considered biologic drugs because they are made by the cells of living organisms. This is in contrast to conventional medications made by chemical synthesis. The 4 CGRP mAbs are all classified as “humanized” monoclonal antibodies. Humanized CGRP mAbs are made in a laboratory by combining part of a human antibody with a small part of a non-human (such as hamster or yeast) monoclonal antibody by a process called recombinant DNA technology. The non-human part of the antibody binds to the target antigen (in this case, either the CGRP ligand (protein) or CGRP receptor), and the human part makes it less likely to be seen as a “foreign antigen” destroyed by our immune system. To explain further, these humanized CGRP mAbs are produced and cloned repeatedly in non-human immune system living cells (hamster ovarian cells or yeast cells), ensuring that they are all of identical genetic material (monoclonal), and their protein structure is modified to increase their similarity to antibody structures produced naturally in humans.

As a review, antibodies are proteins made by living organism cells which bind unique parts of other proteins that are recognized as a “foreign” to that biologic system. For example, when your body is exposed to a virus or bacteria by infection or immunization, your body makes specific antibodies against that microbe to destroy it. If your body encounters that microbe in the future, it remembers it (immune response), and your antibodies attach to it to neutralize and destroy it.

 

How do the CGRP mAbs work for migraine?

The CGRP mAbs target either the CGRP receptor and block it (antagonist) to prevent the CGRP ligand (protein) from binding, or they target the CGRP ligand itself and prevent it from binding (sticking) to the CGRP receptor. Clinically, some patients tend to respond better to the CGRP receptor blockade, whereas others tend to do better with binding the CGRP ligand itself. There is not really any data on this in terms of who may respond to which type of CGRP mAb target, but I’m sure it will be studied further eventually. In general, the CGRP mAbs tend to all be quite effective. However, the point is if one type of CGRP mAb doesn’t work, it doesn’t mean the others won’t work either. I have seen many patients who did not respond to one type of CGRP mAb, but responded dramatically well to another. So, if you do not respond to one type of CGRP mAb target (such as the CGRP receptor), it may be worth trying another type of CGRP mAb target (such as the CGRP ligand). The bottom-line is don’t lose hope if one type doesn’t work well for you!

The CGRP mAbs are administered by injection or infusion because oral absorption is poor and degradation in the gastrointestinal system would inactivate the antibodies before they would even be able to enter the circulatory system. They are systemically absorbed by transport through the lymphatic system and into the blood. Metabolism occurs in the reticuloendothelial system, not the liver or kidneys.

 

How effective are the CGRP mAbs?

All 4 of the CGRP mAbs have shown excellent tolerability, safety, and superior effectiveness in migraine prevention when compared to placebo. Compared to oral preventive therapies which have been the mainstay for decades (discussed here), the CGRP mAbs work much faster and do not require a slow dose titration, as is done with most oral preventives. They are sometimes seen to be effective in just a few days, often within a month, and the data suggests that the longer a patient is on a CGRP mAb, the more effective it is. I typically recommend a minimum of at least 3 months, and if receiving some benefit at that point, at least 6 months is suggested.

The majority of CGRP mAb studies had at least 50% (half) of patients who were 50% responders (migraine days cut in half), which is great! In general, the CGRP mAbs provide an overall average net reduction of around 2 migraine days per month for episodic migraine and 4-6 days for chronic migraine. With that said, this number can be much higher depending on the patient and migraine characteristics being studied, such as baseline migraine frequency.

There are a group of patients that we see called “super responders” because they improve dramatically to having greater than 75% decrease in migraine days, and sometimes even no migraines. In the CGRP mAb studies, about 1/3rd of patients were “super responders”, with many them obtaining 100% reduction in migraine days. Although this is wonderful to see when it happens, it should not be the expectation or goal (nor should this be the goal with any preventive migraine treatment).

 

What are the CGRP mAb side effects and are they safe in pregnancy and breastfeeding?

Side effects are minimal, and very similar to placebo in most of the studies, which is great compared to the frequent side effects seen with most of the oral preventive pills we often use. The most common side effects are listed in the table below, but mild injection site reactions tend to be the most common reported side effect among the 3 subcutaneous self-injection CGRP mAbs. Cumulative data show no immunological (they do not suppress or alter the immune system because they do not have a target within the immune system), cardiovascular, or neurological safety concerns of significance. CGRP is suspected to play a possible role in regulating uteroplacental blood flow, myometrial and uterine relaxation, and in maintaining normal gestational blood pressure. Since the mAbs have a long half-life and can last in the system for 5 months, it is recommended to stop it about 6 months prior to pregnancy planning. The CGRP mAbs are also not recommended to use during breast-feeding since we do not have enough safety data at this time.

 

Can I use a CGRP mAb with Botox injections or with the gepants (Nurtec, Ubrelvy)?

Insurance companies often present various hurdles to using preferred treatment options (the bane of my existence). One common issue for patients with chronic migraine who are receiving Botox injections is that most insurance companies will now make the patient choose between Botox or the CGRP mAb. There is of course no good scientific basis for this, other than the company doesn’t want to pay for both. In fact, there is evidence that using Botox with the CGRP mAbs works better together than with either individually. An abstract presented at the American Headache Society Annual Scientific meeting in June 2020 showed that in patients with chronic migraine and a baseline frequency of 25.7 days per month, the frequency dropped to 14.8 days with Botox, and 9.1 days with Botox plus a CGRP mAb.

A similar insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, but again, no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and had added erenumab (Aimovig). The combination of both successfully aborted 100% of their acute migraine attacks. Certainly we need need larger studies to confirm the suspicion that they likely work together synergistically.

The bottom line is that the CGRP mAbs as a class are all very effective for the majority of patients. Ultimately, the one prescribed will often depend on insurance formulary preferences, but there are no “bad options” among them!

 

Clinical comparisons of the CGRP mAbs

There are currently 4 CGRP mAbs available, and each is detailed and compared below in order of FDA approval and becoming available for use. There are some characteristics for each one which can be used to fine tune selection based on specific patient clinical perspectives.

 

Aimovig (Erenumab)

Aimovig was the first of the CGRP mAbs to come on the scene. It is made by Amgen and was FDA approved for migraine prevention 5/17/18. The antibody is produced by recombinant DNA technology in Chinese hamster ovary cells. It is the only one thus far which targets the CGRP receptor rather that the CGRP ligand (protein) itself. Therefore, it binds to the receptor, blocking the ability of the CGRP ligand to bind to the receptor and activate the migraine. It is dosed by either a 70 mg or 140 mg once monthly subcutaneous autoinjector. Since Aimovig came out first, we have longer term data available for it. At close to 5 years on the 140 mg dose, 77% of patients had a 50% reduction in monthly migraine days, 56% of patients had a 75% reduction in monthly migraine days, and 33% of patients had a 100% reduction in monthly migraine days. The dose can be administered to the abdomen, arm, buttocks, or thigh areas.

In post-marketing observations, there have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) in which most were not serious and occurred within hours of administration, and up to 1 week after. Constipation was noted in the studies to occur in a very small percentage (1% for 70 mg, 3% for 140 mg). In post-marketing observations, there have been further reports of constipation with serious complications as well. Constipation occurs after the first dose in the majority of patients who will have this side effect (keep in mind the vast majority do not). Regardless, if you already have problems with constipation, I typically suggest trying one of the other CGRP mAbs (although it doesn’t mean it still can’t be tried). Post-marketing observations have also shown some worsening of pre-existing hypertension or development of hypertension. This observation was most frequently reported within 7 days of administration. Most of these patients already had pre-existing hypertension, or risk factors for developing it.

 

Ajovy (Fremanezumab)

Ajovy was the 2nd of the CGRP mAbs to come along. It is made by Teva and was FDA approved for migraine prevention 9/14/18. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. It binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It is dosed by either a 225 mg once monthly or 675 mg once quarterly autoinjector or syringe. The dose can be administered to the abdomen, arm, buttocks, or thigh areas. There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as well, typically mild to moderate and occurred hours to 1 month after administration. Ajovy has the least potential for constipation, so if that is an ongoing significant issue for a patient, then I typically suggest trying Ajovy first. Ajovy also has the longest half-life, so if the patient tends to wear off early towards the end of the month, it may help to extend relief closer to the next monthly injection.

Of note, in the Ajovy chronic migraine studies, all patients receiving medication were given a loading dose of 675 mg for dose 1 followed by the standard 225 mg each subsequent month. However, this is not how it is normally dosed clinically for patients doing monthly treatments of 225 mg (no loading dose). Therefore, this initial loading dose could have potentially influenced some of the subsequent data.

 

Emgality (Galcanezumab)

Emgality was the 3rd of the CGRP mAbs to come along. It is made by Eli Lilly and was FDA approved for migraine prevention 9/26/18. Notably, it is the only one which also has FDA approval for prevention of episodic cluster headache, which was received on 6/4/19. It is produced by recombinant DNA technology in Chinese hamster ovary cells. It targets the CGRP ligand, rather than the CGRP receptor. Thus, it binds to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It is dosed by a 240 mg subcutaneous autoinjector for the 1st month only, followed by a 120 mg once monthly injection thereafter. The higher initial loading dose allows for obtaining a rapid steady state concentration level in the blood compared to Aimovig and Ajovy. The dose can be administered to the abdomen, arm, buttocks, or thigh areas. There have been some reports of hypersensitivity reactions (rash, allergic reactions, itching) as well.

 

Vyepti (Eptinezumab)

Vyepti was the 4th and most recent of the CGRP mAbs to become available. It is made by Lundbeck and was FDA approved for migraine prevention 2/21/20. The antibody is produced in Pichia pastoris yeast cells by recombinant DNA technology. It targets the CGRP ligand, rather than the CGRP receptor. It binds very strongly to the CGRP ligand, interfering with its ability to bind to the CGRP receptor and activate the migraine. It comes in 100 mg and 300 mg doses and is dosed once quarterly (every 3 months) by a quick 30-minute infusion. The 100 mg dose is the recommended starting dose which can be titrated as needed to the higher dose later.

This is the only intravenous (IV) option available. Since it is administered IV, it is 100% bioavailable compared to the bioavailability of the other subcutaneous injections of 50-82%. It also reaches Cmax (maximum concentration) in about 30 minutes compared to 5-7 days of the other subcutaneous injections. Therefore, not surprisingly Vyepti showed treatment benefit in the first 7 days, often as early as 1 day post treatment, and showed continued effect through week 4, which is great since many patients on the once monthly self-injection CGRP mAbs often report a wearing off effect as they are approaching their next due injection.

This is certainly a good first line consideration, but also a good option for patients who do not like the thought of giving themselves a once monthly shot, have injection site reactions, or have failed the other CGRP mAbs options. Studies have shown some impressive highlights compared to other mAbs. In both the chronic and episodic migraine studies, almost 31% of patients had 75% or more reduction in migraine days in the 1st month alone. In the chronic migraine studies, about 27% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 39% of patients! In the episodic migraine studies, over 22% of patients had a 75% or more reduction in migraine days over the first 3 months with 100 mg. After the 2nd dose (months 4-6), this increased to over 33.5% of patients.

 

Data comparisons of the CGRP mAbs

The comprehensive table which follows compares all available data between the 4 CGRP mAbs, as I have compiled from a combination of published studies, scientific posters, and supplemental data provided from medical science liaisons from each company. I have highlighted some of the data throughout the table when it is a unique aspect or superior response in that category. All 4 CGRP mAbs have variable highlights that makes them stand out from the others in various categories, but overall they are all very effective options as a medication class. It is important to realize that the data compiled in the table should not be considered as a direct head to head comparison between the medications, and not all data points were looked at for each drug. For each CGRP mAb, there were variations and differences in many trial aspects such as the study designs, how responder rates were calculated, statistical analysis used, trial endpoints, some responses were based on open label portions of trials (in which patients typically report a higher response rate when they know they are receiving the drug and not placebo), varying definitions such as “headache of at least moderate severity”, what defined a “headache” or “migraine day”, preventive medications being used simultaneously, and baseline migraine frequencies included in the studies. The extent of reduction in migraine days can be influenced by the patient’s baseline migraine frequency in both the episodic and chronic migraine studies (high frequency vs lower frequency). For example, some studies included patients with a much higher baseline migraine frequency, and thus the extent of their migraine day reduction may not be as great as a group studied with a lower baseline frequency to start with.

 

  Aimovig (Erenumab) Ajovy (Fremanezumab) Emgality (Galcanezumab) Vyepti (Eptinezumab)
Dosing 70 mg or 140 mg once monthly by subcutaneous autoinjector 225 mg once monthly or 675 mg once quarterly by autoinjector or syringe 240 mg subcutaneous autoinjector for 1st month followed by 120 mg monthly 100 mg or 300 mg quarterly by 30-minute intravenous (IV) infusion
Target CGRP receptor CGRP ligand CGRP ligand CGRP ligand
Half-life 28 days 31 days 27 days 27 days
Median Peak Serum Concentration 6 days 5-7 days 5 days 30 minutes (after infusion)
Steady State 3 months 168 days (6 months) After the 240 mg loading dose After 1st dose
Bioavailability 82% 54-57% N/A 100%
Episodic migraine: Reduction in mean monthly migraine days in month 1 70 mg: -2.32 days

140 mg: -2.72 days Placebo: -0.9 days

675 mg quarterly: -3.3 days

225 mg monthly: -3.5 days

Placebo: -1.7 days

N/A N/A
Episodic migraine: Reduction in mean monthly migraine days in months 1-3 N/A 675 mg quarterly: -3.7 days

225 mg monthly: -3.4 days

Placebo: -2.2 days

 

*Months 1-3 in long term extension study (open label):

675 mg quarterly: -4.7 days

225 mg monthly: -4.8 days

120 mg monthly: -4.1 days

Placebo: -2.1 days

100 mg: -3.9 days

300 mg: -4.3 days

Placebo: -3.2 days

Episodic migraine: Reduction in mean monthly migraine days in months 4-6 70 mg: -3.2 +/- 0.2 days

140 mg: -3.7 +/- 0.2 days

Placebo: -1.8 +/- 0.2 days

N/A 120 mg monthly: -5 days

Placebo: -3 days

100 mg: -4.5 days

300 mg: -4.8 days

Placebo: -3.8 days

Episodic migraine: Reduction in mean monthly migraine days in months 1-6 N/A 675 mg quarterly: -5 days

225 mg monthly: -4.9 days

 

*months 1-3 placebo, months 4-6 open label

120 mg: -4.3-4.7 days

Placebo: -2.3-2.8 days

N/A
Episodic migraine: Reduction in mean monthly migraine days in months 1-12 70 mg: -4.22 +/- 0.22 days

140 mg: -4.64 +/- 0.19 days

Placebo: -1.8 days

675 mg quarterly: -5.2 days

225 mg monthly: -5.1 days

 

*months 1-3 placebo, months 4-12 open label

120 mg: -5.13 days

 

*12 month safety study with no placebo

100 mg: -4.6 days

300 mg: -5.2 days

Placebo: -4 days

 

*Reported as months 7-12

Episodic migraine:

50% or more reduction in migraine days in month 1

70 mg: 32.7%

140 mg: 35.5% Placebo: 15.5%

675 mg quarterly: 44%

225 mg monthly: 47% Placebo: 25%

 

120 mg: 50.8%

Placebo: 23.7%

100 mg: 59.3%

300 mg: 56.3%

Placebo: 40.5%

Episodic migraine:

50% or more reduction in migraine days in months 1-3

70 mg: 41.3%

140 mg: 48.1% Placebo: 26.3%

675 mg quarterly: 44.4%

225 mg monthly: 47.7% Placebo: 27.9%

 

*At month 3 alone (not averaged over months 1-3):

675 mg quarterly: 49%

225 mg monthly: 51% Placebo: 37%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 59%

225 mg monthly: 61%

120 mg: 55%

Placebo: 32%

 

*At month 2 alone:

120 mg: 54.1%

Placebo: 34.5%

 

*At month 3 alone:

120 mg: 57.7%

Placebo: 37.9%

 

 

100 mg: 49.8%

300 mg: 56.3%

Placebo: 37.4%

Episodic migraine:

50% or more reduction in migraine days in months 4-6

70 mg: 43%

140 mg: 50%

Placebo: 26.6%

N/A 120 mg: 67%

Placebo: 43%

 

*At month 4 alone:

120 mg: 65.2%

Placebo: 41.9%

 

*At month 5 alone:

120 mg: 68.6%

Placebo: 43.7%

 

*At month 6 alone:

120 mg: 66%

Placebo: 44.8%

100 mg: 62%

300 mg: 65.3%

Placebo: 51.4%

Episodic migraine:

50% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 65%

225 mg monthly: 60%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 59.3-62.3% days

Placebo: 36-38.6%

N/A
Episodic migraine:

50% or more reduction in migraine days in months 1-12

70 mg: 61%

140 mg: 64.9% Placebo: N/A

675 mg quarterly: 66%

225 mg monthly: 68%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 64.7%

300 mg: 69.4%

Placebo: 55.9%

 

*Reported as months 7-12

Episodic migraine:

75% or more reduction in migraine days in month 1

N/A 675 mg quarterly: 20%

225 mg monthly: 22% Placebo: 10%

 

120 mg: 25.7%

Placebo: 6.5%

 

100 mg: 30.8%

300 mg: 31.5%

Placebo: 20.3%

Episodic migraine:

75% or more reduction in migraine days in months 1-3

N/A 675 mg quarterly: 18.4%

225 mg monthly: 18.5% Placebo: 9.7%

 

*At month 3 alone (not averaged over months 1-3):

675 mg quarterly: 30%

225 mg monthly: 29% Placebo: 10%

120 mg: 30%

Placebo: 14%

 

*At month 2 alone:

120 mg: 31.2%

Placebo: 11%

 

*At month 3 alone:

120 mg: 34.2%

Placebo: 12.8%

100 mg: 22.2%

300 mg: 29.7%

Placebo: 16.2%

Episodic migraine:

75% or more reduction in migraine days in months 4-6

70 mg: 20.8%

140 mg: 22%

Placebo: 7.9%

N/A 120 mg: 42%

Placebo: 24%

 

*At month 4 alone:

120 mg: 41.6%

Placebo: 15.2%

 

*At month 5 alone:

120 mg: 41.4%

Placebo: 15.5%

 

*At month 6 alone:

120 mg: 43.9%

Placebo: 15.8%

100 mg: 33.5%

300 mg: 40.1%

Placebo: 24.8%

Episodic migraine:

75% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 39%

225 mg monthly: 37%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 33.5-38.8%

Placebo: 17.8%-19.3%

 

N/A
Episodic migraine:

75% or more reduction in migraine days in months 1-12

70 mg: 38.5%

140 mg: 40.8% Placebo: N/A

675 mg quarterly: 42%

225 mg monthly: 45%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 41.2%

300 mg: 47.7%

Placebo: 32%

 

*Reported as months 7-12

Episodic migraine:

100% reduction in migraine days in month 1

N/A 675 mg quarterly: 5%

225 mg monthly: 8% Placebo: 2%

 

120 mg: 8.8%

Placebo: 2.2%

 

100 mg: 8.6%

300 mg: 14.9%

Placebo: 5.9%

Episodic migraine:

100% reduction in migraine days in months 1-3

N/A 675 mg quarterly: 0.7%

225 mg monthly: 2.4% Placebo: 0%

 

120 mg: 11%

Placebo: 4%

 

*At month 2 alone:

120 mg: 11.8%

Placebo: 3.7%

 

*At month 3 alone:

120 mg: 12.2%

Placebo: 7.3%

100 mg: 11.4%

300 mg: 16.8%

Placebo: 9.1%

Episodic migraine:

100% reduction in migraine days in months 4-6

70 mg: 3.2%

140 mg: 5%

Placebo: 2.8%

N/A 120 mg: 17%

Placebo: 9%

 

*At month 4 alone:

120 mg: 16.3%

Placebo: 8.5%

 

*At month 5 alone:

120 mg: 17.6%

Placebo: 8.7%

 

*At month 6 alone:

120 mg: 16.5%

Placebo: 9.5%

100 mg: 19.8%

300 mg: 24.5%

Placebo: 14.3%

Episodic migraine:

100% reduction in migraine days in months 1-6

N/A 675 mg quarterly: 18%

225 mg monthly: 20%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

120 mg: 11.5-15.6%

Placebo: 5.7-6.2%

 

N/A
Episodic migraine:

100% reduction in migraine days in months 1-12

70 mg: 19.8%

140 mg: 21.2% Placebo: N/A

675 mg quarterly: 17%

225 mg monthly: 21%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A 100 mg: 26.8%

300 mg: 30.6%

Placebo: 20.5%

 

*Reported as months 7-12

Chronic migraine: Reduction in mean monthly migraine days in month 1 70 mg: -5 +/- 0.42 days

140 mg: -5.1 +/- 0.42 days

Placebo: -2.7 +/- 0.34 days

675 mg quarterly: -4.8 days

225 mg monthly: -4.7 days

Placebo: -2.7 days

120 mg: -4.06

Placebo: -1.78

 

N/A
Chronic migraine: Reduction in mean monthly migraine days in months 1-3 70 mg: -6.6 +/- 0.4 days

140 mg: -6.6 +/- 0.4 days

Placebo: -4.2 +/- 0.4 days

675 mg quarterly: -5 days

225 mg monthly: -4.9 days

Placebo: -3.2 days

 

*Months 1-3 in long term extension study (open label):

675 mg quarterly: -6 days

225 mg monthly: -6.7 days

120 mg: -4.8 days

Placebo -2.7 days

 

*At month 2 alone:

120 mg: -5.01

Placebo: -3.04

 

*At month 3 alone:

120 mg: -5.41

Placebo: -3.39

100 mg: -7.7 days

300 mg: -8.2 days

Placebo: -5.6 days

Chronic migraine: Reduction in mean monthly migraine days in months 4-6 N/A N/A N/A 100 mg: -8.2 days

300 mg: -8.8 days

Placebo: -6.2 days

Chronic migraine: Reduction in mean monthly migraine days in months 1-6 N/A 675 mg quarterly: -6.5 days

225 mg monthly: -7.6 days

 

*months 1-3 placebo, months 4-6 open label

N/A N/A
Chronic migraine: Reduction in mean monthly migraine days in months 1-12 70 mg: -8.5 days

140 mg: -10.5 days

Combined 70 mg and 140 mg: -9.3 days

Placebo: N/A

675 mg quarterly: -7.2 days

225 mg monthly: -8 days

 

*months 1-3 placebo, months 4-12 open label

120 mg: -7.21

 

*12 month safety study with no placebo

N/A
Chronic migraine:

50% or more reduction in migraine days in month 1

70 mg: 23.9%

140 mg: 28.3% Placebo: 11.4%

675 mg quarterly: 33%

225 mg monthly: 36%

Placebo: 19%

120 mg: 26.4%

Placebo 11%

 

100 mg: 54.5%

300 mg: 60.6%

Placebo: 36.1%

Chronic migraine:

50% or more reduction in migraine days in months 1-3

70 mg: 40%

140 mg: 41%

Placebo: 23%

675 mg quarterly: 30.7%

225 mg monthly: 33.3%

Placebo: 19.9%

 

*At month 3 alone (not averaged over months 1-3):

675 mg quarterly: 37%

225 mg monthly: 39% Placebo: 25%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 42%

225 mg monthly: 48%

120 mg: 27.6%

Placebo 15.4%

 

*At month 2 alone:

120 mg: 30.7%

Placebo: 17.7%

 

*At month 3 alone:

120 mg: 35.2%

Placebo: 24.7%

 

100 mg: 57.6%

300 mg: 61.4%

Placebo: 39.3%

Chronic migraine:

50% or more reduction in migraine days in months 4-6

N/A N/A N/A

 

 

100 mg: 61%

300 mg: 64%

Placebo: 44%

Chronic migraine:

50% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 44%

225 mg monthly: 54%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A, however:

 

*At month 6 in open label extension trial:

120 mg: 44.5%

N/A
Chronic migraine:

50% or more reduction in migraine days in months 1-12

70 mg: 53.3%

140 mg: 67.3%

Combined 70 mg and 140 mg: 59%

Placebo: N/A

675 mg quarterly: 53%

225 mg monthly: 57%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A, however:

 

*At month 9 in open label extension trial:

120 mg: 53.9%

 

*At month 12 in open label extension trial:

120 mg: 56.9%

N/A
Chronic migraine:

75% or more reduction in migraine days in month 1

N/A Month 1 in long term extension study (open label):

675 mg quarterly: 21%

225 mg monthly: 21%

N/A 100 mg: 30.9%

300 mg: 36.9%

Placebo: 15.6%

Chronic migraine:

75% or more reduction in migraine days in months 1-3

70 mg: 17%

140 mg: 20.9% Placebo: 7.8%

675 mg quarterly: 9.6%

225 mg monthly: 12.3%

Placebo: 5.4%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 20%

225 mg monthly: 24%

120 mg: 7%

Placebo 4.5%

 

100 mg: 26.7%

300 mg: 33.1%

Placebo: 15%

Chronic migraine:

75% or more reduction in migraine days in months 4-6

N/A N/A N/A 100 mg: 39.3%

300 mg: 43.1%

Placebo: 23.8%

Chronic migraine:

75% or more reduction in migraine days in months 1-6

N/A 675 mg quarterly: 28%

225 mg monthly: 24%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A, however:

 

*At month 6 in open label extension trial:

120 mg: 21.7%

N/A
Chronic migraine:

75% or more reduction in migraine days in months 1-12

70 mg: 27.1%

140 mg: 41.8%

Combined 70 mg and 140 mg: 33.2%

Placebo: N/A

675 mg quarterly: 28%

225 mg monthly: 31%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A, however:

 

*At month 9 in open label extension trial:

120 mg: 27.9%

 

*At month 12 in open label extension trial:

120 mg: 31.1%

N/A
Chronic migraine:

100% reduction in migraine days in month 1

N/A Month 1 in long term extension study (open label):

675 mg quarterly: 6%

225 mg monthly: 5%

N/A 100 mg: 7.9%

300 mg: 13.4%

Placebo: 2.7%

Chronic migraine:

100% reduction in migraine days in months 1-3

70 mg: 4.3%

140 mg: 2.7%

Placebo: 0.4%

675 mg quarterly: 5.3%

225 mg monthly: 4.5%

Placebo: 4%

 

*At month 3 in long term extension study (open label):

675 mg quarterly: 5%

225 mg monthly: 6%

120 mg: 0.7%

Placebo 0.5%

 

100 mg: 10.8%

300 mg: 15.1%

Placebo: 5.1%

Chronic migraine:

100% reduction in migraine days in months 4-6

N/A N/A N/A 100 mg: 17.8%

300 mg: 20.8%

Placebo: 9.3%

Chronic migraine:

100% reduction in migraine days in months 1-6

N/A 675 mg quarterly: 8%

225 mg monthly: 8%

 

*months 1-3 placebo, months 4-6 open label, data is at month 6

N/A N/A
Chronic migraine:

100% reduction in migraine days in months 1-12

70 mg: 6.1%

140 mg: 12.7%

Combined 70 mg and 140 mg: 8.9%

Placebo: N/A

675 mg quarterly: 9%

225 mg monthly: 10%

 

*months 1-3 placebo, months 4-12 open label, data is at month 12

N/A N/A
Side effects:

Nasopharyngitis

70 mg: 3-9.9%

140 mg: 2-11%

Placebo 6-10%

675 mg quarterly: 5-8%

225 mg monthly: <1-8%

Placebo: 4-9%

120 mg: 7.4%

Placebo: 6.5%

100 mg: 6%

300 mg: 8%

Placebo: 6%

Side effects:

Hypersensitivity reactions

70 mg: <1%

140 mg: <1%

Placebo : <1%

675 mg quarterly: <1%

225 mg monthly: <1%

Placebo: <1%

120 mg: 1%

Placebo: 1%

100 mg: 1%

300 mg: 2%

Placebo: 0%

Side effects:

Constipation

70 mg: 1%

140 mg: 3%

Placebo 1%

675 mg quarterly: <1%

225 mg monthly: <1%

Placebo: <1%

120 mg: 1%

Placebo: <1%

100 mg: <1%

300 mg: <1%

Placebo: <1%

Side effects:

Cramps, muscle spasms

70 mg: <1%

140 mg: 2%

Placebo <1%

675 mg quarterly: <1%

225 mg monthly: <1%

Placebo: <1%

120 mg: <1%

Placebo: <1%

100 mg: <1%

300 mg: <1%

Placebo: <1%

Side effects:

Injection site reactions

70 mg: 6%

140 mg: 5%

Placebo 3%

675 mg quarterly: 18-19%

225 mg monthly: 23%

Placebo: 4%

120 mg: 18%

Placebo: 13%

N/A

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

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IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

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Last updated on November 29th, 2020 at 10:00 am

THE BEST MIGRAINE AND HEADACHE PREVENTION TREATMENTS, WHEN SHOULD YOU START A MIGRAINE PREVENTIVE TREATMENT, AND WHEN SHOULD YOU STOP IT?

@Neuralgroover

BACKGROUND

Migraine is a very disruptive disorder to have to deal with. It interferes with patients’ family, work, and social lives. When the burden of migraine becomes excessive on one or more of these life aspects, preventive migraine therapy should be used. In general, if someone is averaging more than 4 migraines per month, preventive treatment should be offered and discussed, although this number is not an absolute. For example, if someone has 1 migraine per month, but it wipes them out for 1 week and they are missing work, there are certainly variations on when preventive medications should be considered, such as this scenario. If the decision to use a preventive migraine medication has been made, there are several important factors to keep in mind in order to optimize treatment success, as discussed below.

 

TIME

Any preventive medication needs an adequate “therapeutic trial”. In short, you need to be patient and give it enough time to work, as well as get to the correct dose. I see patients all the time that tell me their doctor put them on a medication (usually at too low of a dose), and they stopped it after 3 weeks because it “wasn’t doing anything”. Well, it’s not going to do anything that soon, and that is too early to expect any significant improvement. In general, any preventive medication needs 4-6 weeks to begin working, and 2-3 months until full effect is seen (assuming a good dose has been reached). A good rule of thumb is evaluation of response a minimum of 8 weeks after reaching a target therapeutic dose. If there is a partial response at that time, it’s possible that cumulative benefit can continue to occur over 6-12 months. So the decision on whether to continue really depends on how much benefit has been received, and how well the the patient is tolerating the medication. Unfortunately, there is no way to expedite this process. That doesn’t mean the treatment can’t work sooner. However, that is the standard duration of treatment for a medication to have had a fair trial. Finding a migraine preventive is often a trial and error process. If a treatment is not starting to help by at least 8 weeks at a good dose, changing to a different therapy is suggested. However, once an effective treatment is found, the wait is well worth the decline of migraine frequency and severity!

 

DOSE

In addition to an adequate trial duration, an adequate trial dose is also necessary. For example, a common first line medication used for migraine prevention is Topiramate (which is also FDA approved for migraine prevention). I often see patients who come in on 25 mg or 50 mg and have been on that dose for a year or more without much benefit. I discuss with them that the goal dose is at least 100 mg total daily dose, so the dose is too low. For example, in the migraine preventive trials, once patients reached 100 mg and had been at that dose specifically for at least 4 weeks, that is when improvement of statistical significance began. So, I typically start 25 mg at bedtime for 1 week. Then each week increase by 25 mg at bedtime until 100 mg is reached, and then I give a 100 mg pill to begin. I tell them if there is no improvement starting after at least 4 weeks from reaching the 100 mg dose specifically, let me know. I usually dose it all at bedtime which can help limit side effect potential (since you’ll be sleeping). However, it is generally meant to be taken as a twice daily medicine (such as 50 mg twice daily), and most patients tolerate that fine too.

 

With that said, patients can certainly respond to low doses of medications. However, if improvement has been minimal after a month of a lower dose, it is always a good idea to begin titration up to a better dose. The American Headache Society and American Academy of Neurology published guidelines of migraine preventive medications which includes common goal dose targets for some of these preventive medications here.

 

TREATMENT SELECTION

There are many preventive treatments used, although most of them are considered “off-label” for migraine prevention. This means they are not actually FDA approved for migraine prevention, but there is enough evidence based on research trials or clinical experience to warrant them as a valid option to try. As far as true FDA approved oral (pills by mouth) preventive medications, there are 4 available that have this distinction; Topiramate, Divalproex, Propranolol, and Timolol. There are also a number of natural supplements which have evidence for migraine prevention, and those are detailed and discussed here.

 

The categories of oral preventive migraine medications all sound bizarre. They consist of anti-seizure (anti-convulsant), anti-depressant/anti-anxiety, and anti-hypertension (blood pressure) medications. It is important for patients to know that the medicine is being used specifically for migraine. I often see patients who say they didn’t start the medicine their doctor prescribed because they got home, Googled it, and they tell me, “I’m not depressed”. I explain the reasoning for the medication and that it is not for depression, but for migraine prevention since there are overlapping electrical pathways between many of these types of disorders. Furthermore, there are select medications within each of these categories that have evidence from trials and clinical experience for migraine prevention, as listed here and here. For patients that have chronic migraine (15 or more headache days per month with 8 or more days having migrainous features), Botox is another highly effective option to consider.

 

It is also important to know that the medications in each of these medication classes are not a “one size fits all” for every medicine within that category. For example, there is no good evidence for migraine prevention in the SSRI (selective serotonin reuptake inhibitors) anti-depressant/anti-anxiety medication category (Fluoxetine, Sertraline, Escitalopram, Citalopram, etc.). However, there is evidence for benefit in some of the SNRIs (serotonin and norepinephrine reuptake inhibitors) such as Venlafaxine XR, Duloxetine, as well as some of the TCAs (tricyclic antidepressants), primarily Amitriptyline and Nortriptyline. Similarly, there are select medications within the anti-seizure/anti-convulsant category which have the best evidence (Topiramate, Divalproex), as well as the anti-hypertension category (Propranolol, Metoprolol, Atenolol, Nadolol, Verapamil).

 

There are now 4 monoclonal antibody CGRP receptor antagonists which have this FDA approval for migraine prevention also. Three of them are once monthly auto/self-injections (Aimovig, Ajovy, Emgality), and one is a once quarterly (every 3 months) 30 minute IV (intravenous) infusion (Vyepti). In general, these are an option for those with 4 or more migraines per month on average.  The great thing about these treatment options as opposed to standard pill options is that they do not require a gradual dose escalation, they tend to have a much more rapid onset of improvement, and they have very low side effect risk. These medications are all discussed in much greater detail and comparison here.

 

Neuromodulatory devices that are FDA cleared for migraine prevention are also available and include sTMS (SAVI, SpringTMS, sTMS mini),  eTNS (CEFALY), and nVNS (GAMMACORE), all of which are discussed in much greater detail here. There are also nutraceuticals and supplements which have good evidence for migraine prevention. Yoga, relaxation and wellness therapies are also helpful in migraine prevention.

 

An exciting development is that there are 2 migraine preventive medications in the new gepant classification which are currently in clinical trials, and showing good evidence of effectiveness. They are both oral pills and include Atogepant and Rimegepant (currently FDA approved for abortive migraine treatment under the name Nurtec ODT). So these will open up another new class of preventive migraine medications engineered purely for migraine treatment!

 

When choosing a preventive treatment, I like to fine-tune the treatment to “hit as many birds with one stone”. In other words, pick something that will not only help with migraine prevention, but may also help with other medical conditions at the same time. Doing this can allow you to help minimize the number of medications used overall, by using something with benefit for several disorders in addition to the migraine. For example, if someone has depression or anxiety, targeting their migraine preventive medication with an anti-depressant/anti-anxiety category would make sense. If the patient has other chronic musculoskeletal pain issues, fibromyalgia, occipital neuralgia, etc., the SNRIs and the TCAs are good considerations. If the patient has insomnia, Amitriptyline or Nortriptyline are great options. If they have seizures, an anti-seizure medication such as Topiramate or Divalproex would make sense. If they are overweight, Topiramate also causes weight loss. Divalproex is another anti-seizure medicine which is also FDA approved for migraine prevention. However, this should be avoided when possible in young women of child-bearing age given the high risk of congenital birth defects while taking it (and most pregnancies are unplanned).

 

Here are some treatment considerations to take into account for migraine preventive therapy in addition to the following medical conditions the patient may also have:

-Obese/Overweight: Topiramate, Topiramate ER/XR (extended release), Zonisamide (All can cause weight loss, so also use with caution if patient is extremely thin to limit further weight loss.) If they improve with Topiramate but have side effects, changing to Topiramate ER/XR (extended release) or Zonisamide tend to have similar benefit with less side effects. Would avoid Amitriptyline, Nortriptyline since there is a risk of weight gain for some.

-Underweight/Excessively thin: Amitriptyline, Nortriptyline

-Depression and/or anxiety: Venlafaxine ER, Duloxetine, Amitriptyline, Nortriptyline, Desvenlafaxine

-Mood disorder such as bipolar or psychosis: Divalproex, Topiramate, Carbamazepine

-Anxiety without depression: Venlafaxine ER, Amitriptyline, Duloxetine, Nortriptyline, Desvenlafaxine, Propranolol

-Insomnia: Amitriptyline, Nortriptyline

-Fatigue/Low energy: Venlafaxine ER, Duloxetine (these can be energizing for many, so are best taken in morning)

-Hypertension: Propranolol, Metoprolol, Nadolol, Atenolol, Lisinopril, Candesartan, Verapamil

-Palpitations: Propranolol, Metoprolol, Nadolol, Atenolol

-Chronic musculoskeletal pains, fibromyalgia, neuropathy/nerve pains: Amitriptyline, Duloxetine, Nortriptyline, Gabapentin

-Non-oral route needed or preferred: Once monthly self/auto injections of monoclonal antibody CGRP receptor antagonists (Aimovig, Ajovy, Emgality) or once quarterly 30 minute IV infusion (Yvepti), which are all detailed here. Botox is another non-pill option for those averaging 15 or more headache days per month with at least 8 of those days having any migrainous features (throbbing, nausea, sensitivity to light (photophobia) or sound (phonophobia)) for 3 or more consecutive months (chronic migraine). Neuromodulatory devices that are FDA cleared for migraine prevention are also available and include sTMS (SAVI, SpringTMS, sTMS mini),  eTNS (CEFALY), and nVNS (GAMMACORE), all of which are discussed in much greater detail here.

-Averaging 15 or more headache days per month with at least 8 of those days having any migrainous features (throbbing, nausea, sensitivity to light (photophobia) or sound (phonophobia)) for 3 or more consecutive months (chronic migraine): Botox (Onabotulinumtoxin-A) injections every 3 months according to the PREEMPT chronic migraine treatment protocol. This is the only truly FDA approved medication for prevention of chronic migraine as of 2010. Any of the above listed medications are also options to consider, and most insurances will require failure of at least 2 classes of preventative oral medications before Botox is approved anyway, but this varies by insurance.

 

EXPECTATIONS

Expectations in migraine management are important. If your expectation is that your migraines will stop completely when you use preventive medications, you will be sorely disappointed. Of course it can certainly happen, but that is rare and should never be the expectation or goal. The goal of preventive therapy is a decrease in migraine frequency and/or severity of attacks (optimally both) to some extent to make them more tolerable and less intrusive into life. A general goal is 50% improvement in frequency and/or severity. Some patients can get much more than that, while others get much less (which would signal trials of a different medication class). With that said, success with migraine preventive benefit can also be considered in significant decreases is migraine attack duration or severity, reduction in migraine associated disability, improving the patient’s functioning in various areas of life, improvements in quality of life, and improvement in acute treatment responses. In general, studies estimate that about 45% of patients on conventional preventive therapy (such as oral medications) receive 50% reduction in monthly migraine days. Thus, 55% will receive less improvement than this. The CGRP mAbs tend to have a higher rate of improvement then conventional treatments as detailed here.

 

WHEN TO STOP

There is no absolute answer of when to stop preventive therapy. It depends on how well one is doing, how long they have been doing well, and how much they want to get rid of treatments. Some people want off as soon as they can, others prefer to stay on for years since they are doing very well with few migraines, and don’t want to “rock the boat”. In general, the goal is to continue preventive therapy until the patient is doing significantly better for at least 3 months, but preferably closer to 6 months or so. I always make sure to tell patients that preventive medicines or treatments are not necessarily meant to be a life-long commitment. Rather, we use these treatments to “reboot” and “reset” the brain’s electrical system to have less frequent and/or severe migraines, and then try to sneak away off the medications once they are consistently doing better.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on December 4th, 2020 at 05:44 am

CEFALY vs. NERIVIO vs. GAMMACORE vs. SPRING TMS. NEUROMODULATORY DEVICES FOR MIGRAINE AND CLUSTER HEADACHE: WHAT ARE THE DIFFERENCES AND WHICH IS BEST?

@Neuralgroover

 

 

Cefaly vs. Nerivio, Nerivio vs. GammaCore, Cefaly vs. GammaCore, Nerivio vs. SpringTMS, Cefaly vs. SpringTMS, GammaCore vs. SpringTMS. These are common questions that patients have about migraine neuromodulation devices. Many patients do not respond to conventional migraine abortive medications, they do not tolerate them, do not like taking medications, or they cannot take them due to medical contraindications. These standard migraine abortive options are discussed here. Luckily, there have been several neuromodulatory devices for the treatment of migraine which have entered the market over the last few years. These non-invasive neuromodulation devices open up new migraine treatment options for those in these sensitive and difficult patient populations, including pregnancy as well. These also avoid the complications of medication overuse headache (rebound headache) that is often an issue with using too much abortive migraine medication, as discussed in greater detail here.

But do they really work? Is one better than the other? Do they hurt? Are they used for abortive or preventive treatment? Are they expensive? Does insurance cover them? How do they compare, and is one best for you? This blog will address all of these questions.

These devices include Single-Pulse Transcranial Magnetic Stimulation (sTMS) (SAVI, SpringTMS, sTMS mini), external trigeminal nerve stimulation (eTNS) (Cefaly), noninvasive Vagus Nerve Stimulation (nVNS) (GammaCore), and the most recent, wireless remote electrical neuromodulation (REN) (Nerivio). We’ll discuss these devices in the order in which they became available and FDA cleared. The table further down is a summary of comparison data between devices gathered from published studies and directly from the companies as well. It’s important to keep in mind that the data in this table are not from head to head studies between devices. Each of these devices had separate study designs (which were quite varied), and the results of those studies is what is reflected here, certainly not a direct comparison between devices. All devices require a prescription from your doctor. Pricing and intermittent promotional specials can be found on each device’s website and some of these are discussed below. Sometimes the long-term costs equal out or can even be less than the cumulative cost of many medications and treatments used abortively and preventively.

 

SINGLE-PULSE TRANSCRANIAL MAGNETIC STIMULATION (sTMS)

The first device which was FDA cleared was the Single-Pulse Transcranial Magnetic Stimulation (sTMS), made by the company eNeura. It was initially FDA cleared for the acute treatment of episodic migraine with aura in adults in December 2013. It then received FDA clearance for both acute and preventive treatment of migraine in adults in 2017. This clearance was then expanded to the acute and preventive treatment of migraine in children 12 years of age and older in February 2019. Prior models included the Spring TMS and sTMS mini. The newest model, SAVI, is currently the only FDA cleared device for both the acute and preventive treatment of migraine in adults and children 12 years of age or older. Since the device is used acutely and preventively, the FDA approved it for a maximum of 17 pulses per day.

The user holds the device against the back of the head, and presses a button to release a very short magnetic pulse at the onset of aura or a migraine attack with or without aura. The magnetic pulse delivers a fluctuating magnetic field which induces a mild electric current through the skull and onto the surface of the occipital cortex (visual cortex) of the back part of the brain. This modifies the electrical excitability and hyperactivity of the cortical neurons to block or prevent the onset of a migraine from evolving to a full-blown migraine. The device stops cortical spreading depression, which is suspected to be the basis of migraine aura in the occipital cortex. It is also suspected to interfere with thalamocortical pain pathways that are normally activated during a migraine. The company offers a 90-day money back guarantee, and it is typically rented in 3-month increments.

The most common side effects were mild and brief light-headedness/dizziness, tingling over the back of the head where treatment is performed, brief tinnitus (ringing in ears), nausea, and muscle spasm. You should not use this device if you have a cardiac pacemaker, vagus stimulator (VNS) or other implanted neurostimulator, implanted cardioverter defibrillator (ICD) or any implanted medical device that stimulates the body or uses any signal from the body. It is also suggested that patients with implants affected by a magnetic field should not use this device. Examples of such implants include aneurysm clips or coils, cochlear implants, cerebral spinal fluid shunts, bullets or pellets lodged in the head or upper body, metal plates, screws, staples or sutures in skull, neck, shoulders, arms or hands, and facial tattoos with metallic ink. Dental implants, fillings or other dental appliances are okay to use the device.

Acute migraine treatment consists of 3 sequential pulses (early) at the onset of a migraine (aura or pain). Then wait 15 minutes. If needed, treat with an additional 3 pulses. Then wait another 15 minutes. If needed, treat with an additional 3 pulses. Studies reported that 39% of patients were pain free at 2 hours.

Prevention treatment consists of 4 pulses twice daily. This is performed by giving 2 consecutive pulses, waiting 15 minutes, and then repeating 2 consecutive pulses. Studies reported that 46% of patients had a greater than 50% reduction in monthly headache days and averaged approximately 3 less migraine days per month.

Unfortunately, eNeura filed for Chapter 7 bankruptcy on 8/7/20, so it is unclear what exactly the future holds for these sTMS devices.

 

CEFALY

Cefaly was the next neuromodulation migraine treatment device that became available, and is an external trigeminal nerve stimulation (eTNS) device (similar to a TENS unit mechanism). It is made by Cefaly Technology. It works by neurostimulation of the trigeminal nerve branches in the forehead. It was FDA cleared for the prophylactic (preventive) treatment of migraine in adults in March 2014, and acute treatment of episodic migraines in adults in November 2017. The Cefaly Dual device is the most recent model, and has settings for both acute and preventive migraine treatment. The company offers a 60-day money-back guarantee. As of 10/13/20, the Cefaly Dual neuromodulation device became the first FDA-approved trigeminal nerve stimulator for migraine treatment available without a prescription and can now be purchased over-the-counter. The Cefaly Dual kit includes the Cefaly device, 1 electrode (good for 20 uses), power adapter, charging cable, and storage case. It normally retails for $499. Three packs of electrodes are $25, or by a cost-saving subscription service.

Cefaly treatment is often described as a mild buzzing and pressure sensation. It should be avoided in patients with implanted metallic or electronic devices in the head, or who have a cardiac pacemaker or implanted or wearable defibrillator.

Acute migraine treatment consists of a 1-hour session. It may be repeated for a second 60-minute session if the migraine pain is not relieved within two hours, or if another migraine attack occurs. Studies reported that at 1 hour, 32% were pain free and 79% had significant pain relief. At 2 hours, 17% were pain free and 65% significant pain relief.

Migraine prevention consists of a nightly 20-minute session. Studies reported a 29.7% decrease in migraine attacks, and 38.1% of patients received at least 50% decrease in migraine attacks.

 

VAGUS NERVE STIMULATOR (GAMMACORE)

Noninvasive Vagal Nerve Stimulation (nVNS) is made possible by a hand-held device called GammaCore, from the company ElectroCore. The most recent model is called GammaCore Sapphire. It was initially FDA cleared for the acute treatment of episodic cluster headache in adults in April 2017, followed by the acute treatment of migraine in January 2018, cluster headache prevention in November 2018, and migraine prevention in March 2020. It was the first and remains the only therapy which is FDA-cleared for the prevention of cluster headache This device is placed over the vagus nerve on the side of the neck, just below the angle of the jaw where the pulse of the carotid is felt in the neck. It is suspected that the device works by suppressing cortical spreading depression (a central process in migraine and aura formation), and blocking and modulating the thalamocortical, trigeminovascular and trigeminocervical pain pathways that are normally activated during a migraine.

Acute migraine treatment consists of 2 two-minute stimulations. If the pain remains 20 minutes after the start of the initial treatment, 2 more two-minute stimulations are given. Two more two-minute stimulations may be applied if the pain remains 2 hours after the start of the initial treatment. Studies showed significant pain relief in as soon as 30 minutes, and reported that at 1 hour, 21% were pain free and 35.8% had significant pain relief. At 2 hours, 30.4% were pain free and 40.8% significant pain relief. GammaCore reduced pain intensity over 3x greater than sham (fake device) at 60 minutes and over 6x greater at 120 minutes, and reduced the need for other rescue medications.

Preventive migraine treatment is done by giving 3 treatments daily (morning, mid-day, and night) consisting of two consecutive 2-minute stimulations. Studies showed a 29% reduction in migraine days per month when used preventively, although this number was even higher in those with aura at a 35.8% decrease. Overall, 33.6% of patients received at least a 50% decrease in migraine frequency.

Acute cluster headache treatment is done by giving 3 two-minute stimulations. After completing the 3rd stimulation, the user waits 3 minutes. If pain remains, 3 more two-minute stimulations can be applied. You may treat up to 4 attacks (8 treatments) for a total of 24 stimulations per day. Significantly more episodic cluster attacks treated with GammaCore were pain-free at 15 minutes vs those treated with sham   (47.5% vs 6.2%). Combined study data showed that significantly more (over 2-4x greater response) episodic cluster headache patients responded (no pain or mild pain) to GammaCore at 15 minutes for 50% or more of all treated attacks vs those receiving sham (34.2-64.3% vs 14.9-15.4%). At 15 minutes, there were also significant reductions in pain duration and intensity with GammaCore compared to sham.

Preventative cluster treatment is done by giving 2 treatments (morning and night) consisting of 3 two-minute stimulations. Weekly attack frequency decreased by 40% from baseline when GammaCore was added to standard of care therapy. There was a 57% decrease in the frequency of acute medication use when GammaCore was added.

GammaCore treatment is often described as a deep vibration. GammaCore should not be used with an active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device. It should be avoided in patients who have a metallic device such as a stent, bone plate, or bone screw implanted at or near their neck, are using another device at the same time (e.g., TENS Unit, muscle stimulator) or any portable electronic device (e.g., mobile phone).

 

NERIVIO

The Nerivio device is made by the company Theranica. It is a wireless remote electrical neuromodulation (REN) device wearable for the acute treatment of migraine applied to the upper-arm. It was FDA-cleared for the acute treatment of episodic migraine in adults in May 2019. In October 2020, FDA clearance was extended to acute treatment of migraine in chronic migraine patients as well. Each device provides 12 treatments. When the device is used up, it is recycled and a new refill device is sent. It is the most economical option on the market. Costs can often be similar to monthly triptan prescription costs. The device works through an app downloaded on your smartphone which controls the strength and treatments. The device itself is an arm band that easily straps around the upper arm, and was recognized in TIME Magazine’s annual list of the 100 Best Inventions in 2019. In October 2020, Nerivio became the first neuromodulation device to receive a pharmacy/medical benefit.  is available for $10 on the initial prescription for anyone with any form of medical or pharmaceutical insurance, including government insured patients such as Medicare and Medicaid! Commercially insured patients may have their Co-pay reduced to $0 on future refills, while government insured patients will pay $99 for refills. No patient ever pays more than $99 for a refill, and most will hopefully pay $0 on refills.

It delivers electronic pulses into the skin to generate a proprietary “Conditioned Pain Modulation” response which helps to abort the effects of a migraine in patients with or without aura. Nerivio stimulates specific sensory nerves of the upper arm which normally sense pain. The stimulation from the device is not strong enough to actually trigger pain for the user, but the signal still travels to the brainstem, as it normally would. From here, it interferes and blocks the ongoing activated electrical circuitry of the migraine, and helps to abort it. Many think this is basically a TENS unit, but it is not. It has a proprietary stimulation signal which targets specific pain transmitting nerve fibers that disrupts the electrical activity of a migraine centrally from a remote location peripherally (on the arm).

The device is applied within 60 minutes (preferably at onset) of a migraine headache or migraine aura and stimulation is performed for 45 minutes. It is described as a vibrating sensation. Studies showed that 66.7% of patients had significant pain relief at 2 hours, and 37.4% of patients achieved complete pain relief at 2 hours. Furthermore, 89.7% of patients studied avoided having to take other abortive medications when treating with Nerivio.

Side effects may include a temporary sensation of warmth, local tingling, numbness in the arm, pain in the arm, or redness of the skin, although 96.4% of patients studied did not report any device related adverse events. It is recommended to avoid in congestive heart failure, severe cardiac or cerebrovascular disease and uncontrolled epilepsy. It should not be used with certain medical devices such as a pacemaker or hearing aid implant. Using Nerivio with other implantable medical devices could potentially cause electric shock, electrical interference, or other injury. So it should not be used near any metallic implants.

 

  sTMS Cefaly GammaCore Nerivio
Acute Migraine Yes Yes Yes Yes
Preventive Migraine Yes Yes Yes No
Acute Cluster No No Yes No
Preventive Cluster No No Yes No
1-hour migraine pain free N/A 32% (13% sham) 21% (sham 10%) N/A
1-hour migraine pain relief N/A 79% (39% sham) 35.8% (sham 24.4%) N/A
2-hour migraine pain free 39% (sham 22%) 17% (sham 7%) 30.4% (sham 19.7%) 37.4% (18.4% sham)
2-hour migraine pain relief N/A 65% (sham 52%) 40.8% (sham 27.6%) 66.7% (38.8% sham)
Migraine preventive relief 46% had > 50% decrease in monthly HA days (20% “statistically derived” placebo) and averaged 3 less migraine days/month 29.7% decrease (sham 4.9%)

38.1% received at least 50% decrease in migraines (sham 12.12%)

29% decrease (sham 18%)

35.8% decrease in patients with aura

33.6% received at least 50% decrease in migraines (sham 23.4%)

N/A

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on November 24th, 2020 at 04:45 pm

VISUAL SNOW, PERSISTENT MIGRAINE AURA, MIGRAINOUS STROKE, AND WHAT YOU SHOULD KNOW.

@Neuralgroover

INTRODUCTION

The International Classification of Headache Disorders-3 (ICHD-3) classifies persistent aura without infarction (stroke) and migrainous infarction as two of the four reported complications of migraine, both of which are very rare. The other two reported complications of migraine include status migrainosus and migraine aura-triggered seizure, but these will not be discussed here1. 

 

MIGRAINE PATHOPHYSIOLOGY

In order to discuss persistent migraine aura without infarction or migrainous infarction, it is crucial to understand migraine pathophysiology, which involves a multitude of complex processes throughout the cortex, brainstem, and cerebral vasculature. The pathophysiology of migraine has evolved from the vascular theory to the neurovascular theory of migraine. The older vascular theory proposed by Wolff viewed migraine as beginning with cerebral vasospasm causing focal ischemic (lack of blood flow) symptoms (aura) followed by extra and/or intracranial hyperperfusion (excess blood flow) from vasodilatation leading to the migraine pain. 2 This theory made good sense for how stroke or persistent neurological symptoms could develop, from the period of cerebral vasospasm and constriction. However, in later studies of migraine with aura, regional hypoperfusion developed before and outlasted focal neurologic symptoms, and this dissociation of time, perfusion changes and symptoms indicated that these neurologic symptoms were not caused by truly ischemic blood flow, but rather the apparent hypoperfusion is secondary to a disturbance in brain metabolism. 3-6

Lashley first described his own visual aura and hypothesized that the aura was due to a spreading abnormality migrating over the visual cortex at a rate of 3-5 mm per minute in 1941. 7 In 1944, Leão described spreading depression as a wave beginning with a brief neuronal burst associated with transient increased blood flow followed by a longer lasting neuronal electrical suppression with decreased blood flow in an animal model. 8-10 Subsequent studies confirmed this initial focal hyperemia followed by posteriorly to anteriorly spreading oligaemia (reduced blood flow) and regional cerebral blood flow reduction, which does not reach critical ischemic values, in a wave-like manner at approximately 2-5 mm per minute. This spreading regional cerebral blood flow reduction is independent of arterial territories, and does not cross cytoarchitectural borders or neuronal discontinuity such as the central sulcus or lateral sulcus, confirming impaired neuronal metabolism with subsequent regional cerebral blood flow reduction, rather than true ischemia. 3-6 This remains the basis for the now current neurovascular theory of migraine.

Most studies have been unable to show significant ischemic cerebral blood flow changes during migraine attacks. Results have shown alterations in cerebral blood volume, relative cerebral blood flow, and tissue mean transit time (MTT) in the grey matter of the occipital cortex contralateral (opposite) to the side of aura during an attack, while others have shown global cerebral blood flow increase, and others have shown hypoperfusion of the whole hemisphere, but never true ischemic hypoperfusion. 11-14 Notably, cerebral blood flow changes correlate poorly with migraine pain, and neurogenic inflammation in the trigemino-vascular system is suspected to be the primary cause of migraine pain, rather than arterial vasodilatation. 11,15

 

PERSISTENT AURA WITHOUT INFARCTION

The ICHD-3 defines persistent aura without infarction as aura symptoms persisting for 1 week or more without evidence of infarction on neuroimaging. It should occur in a patient with a history of migraine with aura and typical of previous auras except that one or more aura symptoms persist for 1 week or more. Neuroimaging must show no evidence of infarction, and symptoms are not better accounted for by another ICHD-3 diagnosis. The aura symptoms are often bilateral and may last for months or years. It is important to differentiate persistent aura without infarction from symptomatic aura as a result of cerebral migrainous infarction. Aura symptoms lasting more than 1 hour and less than 1 week are classified as probable migraine with aura.

There are two primary types of persistent migraine aura that are described. One is persistent primary visual disturbance in which the patients describe “visual snow” or “television static” in both visual fields in both eyes, and some report additional intermittent scotoma or oscillating lights. 16 The other is persistent migraine aura with typical aura, in which patients describe scotoma, fortification, or oscillation in one hemifield (one side of vision), and does not go away (sometimes also called status aura). 16

The specific pathophysiology of persistent migraine aura without infarction remains unknown, although several theories exist. Some of these theories include low cerebral magnesium levels, abnormal cerebral energy metabolism, greater cerebral reactivity of NMDA receptors to glutamate, lower threshold for triggering cortical spreading depression, low cortical preactivation due to thalamocortical hypoactivity, sustained hyperexcitability of the visual cortex without significant dynamic modulation, sustained cortical neuronal dysfunction, intracortical disinhibition, loss of inhibitory GABA-ergic interneurons resulting in a network imbalance leading to a reverberating cycle of cortical spreading depression (small cortical infarctions below MRI sensitivity in the occipital cortex has been one proposed mechanism), or a combination of any of these possibilities. 16-21

The evaluation for persistent migraine aura without infarction should focus on excluding intracranial pathology, primarily stroke, although other intracranial etiologies need to be excluded. Brain MRI scan is preferable with MRA of the brain and neck (to also assess the arteries), but if medically contraindicated, brain CT scan with CTA of the brain and neck (to assess the arteries) can be pursued. Contrast administration for either type of scan is suggested, although not mandatory. A detailed neuro-ophthalmologic examination is also required. Studies investigating other imaging modalities for persistent migraine aura without infarction, including FDG-PET, MR-PWI, and Tc99m-HMPAO-SPECT, have shown conflicting and inconsistent results.

Treatment for persistent aura without infarction is undefined, and generally based on medication trial and error. The literature reveals an extensive list of medications tried and failed, with most attempting to target neuronal hyperexcitability. Treatments and medications which have been assessed have included anticonvulsants (lamotrigine, topiramate, valproic acid, gabapentin, phenobarbital, phenytoin, carbamazepine), benzodiazepines (clonazepam, diazepam), antidepressants (amitriptyline, cymbalta, buspirone, fluoxetine, nortriptyline, sertraline, dothiepin), anti-hypertensive (atenolol, acetazolamide, flunarazine, metoprolol, propranolol, verapamil, nifedipine, nimodipine, furosemide), NSAIDs (acetylsalicylic acid, ibuprofen, flurbiprofen, diclofenac, indomethacin, naproxen) analgesics (acetaminophen, butalbital, codeine), and a variety of other medications (baclofen, citicholine, ergotamine, ketamine, cyproheptadine, methylphenidate, methylprednisolone, pizotifen, prochlorperazine, promethazine, sumatriptan, memantine). The vast majority of these medications have shown no evidence of benefit. 16 Of them, lamotrigine has shown the most evidence of benefit, while divalproex sodium, baclofen, sertraline, nifedipine, nimodipine, acetylsalicylic acid, and furosemide have reported varying degrees of benefit from complete to partial resolution of symptoms. 16   

Abortive migraine options can include the gepants (Ubrelvy, Nurtec ODT), ditans (Reyvow), NSAIDs and other conventional abortives, although triptans and ergots should be avoided.

 

MIGRAINOUS INFARCTION

The ICHD-3 defines migrainous infarction as one or more migraine aura symptoms associated with an ischemic brain lesion in a correlating anatomical clinical territory demonstrated by neuroimaging. It should occur in a patient with a history of migraine with aura and typical of previous attacks except that one or more aura symptoms persists for more than 60 minutes, and it should not be better accounted for by another diagnosis. Clearly associating an ischemic stroke and a migraine attack in a migraine sufferer can be difficult. Cerebral infarction of other etiologies can coexist with migraine, can present with symptoms resembling migraine with aura, or cerebral infarction can occur during an attack of migraine with aura, and this is the only scenario that would be consistent with migrainous infarction.

Migrainous infarction occurs predominantly in the posterior circulation and in younger women. In the Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis (CAMERA) study, these infarct-like white matter lesions found in migraineurs (primarily in migraine with aura) were predominantly located in the posterior circulation, especially in the cerebellum. 22,23 However, these infarctions are not necessarily considered migrainous infarctions and the mechanisms are unclear.

Multiple studies have confirmed the association with increased stroke risk in women with migraine with aura. Women younger than age 45 who have migraine with aura, have a 2 fold increased risk of stroke. Notably, migraine without aura does not appear to have the same increased risk. This risk increases to 6 fold in the setting of oral contraceptive use containing estrogen, and more than 9 fold with combined smoking and oral contraceptive use. 24 Menstrual migraine and the use of hormonal therapy and birth control is discussed in more detail here. Women who are smokers and have migraine with aura should consider estrogen containing oral contraception a contraindication. Oral contraceptive use in non-smoking women with migraine with aura is more controversial. The World Health Organization (WHO) and American College of Obstetrics and Gynecology (ACOG) suggest that in non-smoking women under age 35 with migraine with aura, there is an acceptable lower risk of oral contraceptive use. However, if they are over age 35, the risk is unacceptably higher and oral contraceptive use is contraindicated. According to the International Headache Society (IHS), in non-smoking women with migraine with aura who are either younger or older than age 35, taking into account other risk factors should individualize the decision for oral contraceptives. 24 These would include ischemic heart disease, family history of early heart disease at a young age of less than 45 years old, heart disease with concern for emboli such as atrial fibrillation, uncontrolled hypertension, hyperlipidemia, diabetes, obesity, systemic disease associated with increased stroke (connective tissue disease, sickle cell, hypercoagulability), etc. In women with an increased risk of stroke, and especially with multiple vascular risk factors, non-estrogen methods of birth control such as progesterone-only forms of contraception should be recommended.

Research has also reported that after high blood pressure, migraine with aura was the second strongest single predictor of heart attack and strokes, ahead of diabetes, smoking, obesity, and family history of early heart disease. 25 This increased risk was not seen in migraine without aura. It is not necessarily thought that migraine with aura causes the stroke, but rather it is a marker for young women at a greater risk for cardiovascular disease. However, the reasons for these associations are unclear, likely multifactorial, and clearly need to be further defined. Traditional vascular risk factors such as hypertension, smoking, diabetes and hyperlipidemia still show the strongest contribution to cardiovascular disease, so these should be optimized, especially in those with migraine with aura to reduce risk of both heart disease and stroke. 25

Some theorized mechanisms of migrainous infarction include vasospasm, endothelial dysfunction, vascular endothelium-related hypercoagulability during cortical spreading depression and the aura phase, or genetic alterations of the wall of the small cerebral arterial vessel walls. 26-31

The evaluation for migrainous infarction is similar to that of persistent migraine aura without infarction. By definition, an ischemic infarct in a correlating anatomic area to symptoms should be seen on MRI or CT of the brain. This warrants a further standard stroke evaluation, including imaging of the intra and extracranial vasculature (including carotid arteries), as well as cardiac evaluations beginning with transthoracic echocardiography. Electrocardiogram and telemetry should also be pursued to evaluate for paroxysmal arrhythmias such as atrial fibrillation.

Treatment of migrainous infarction is the same as with any ischemic stroke. The initial goal is to evaluate for potentially treatable etiologies (such as cardioembolic source) and treat accordingly. Otherwise, secondary stroke risk factor modifications are the goal and include antiplatelet therapy in combination with optimal control of blood pressure, hypertension, hyperlipidemia, diabetes, tobacco cessation, and healthy lifestyle changes.

Abortive migraine options can include the gepants (Ubrelvy, Nurtec ODT), ditans (Reyvow), NSAIDs and other conventional abortives, although triptans and ergots should be avoided.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

REFERENCES

  1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia 2013;33:629-808.
  2. Wolff HG. Headache and Other Head Pain. New York: Oxford University Press, 1963.
  3. Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981;9:344-52.
  4. Lauritzen M. Pathophysiology of the migraine aura. The spreading depression theory. Brain 1994;117 ( Pt 1):199-210.
  5. Lauritzen M, Skyhoj Olsen T, Lassen NA, Paulson OB. Changes in regional cerebral blood flow during the course of classic migraine attacks. Ann Neurol 1983;13:633-41.
  6. Lauritzen M,  Olesen J. Regional cerebral blood flow during migraine attacks by Xenon-133 inhalation and emission tomography. Brain 1984;107 ( Pt 2):447-61.
  7. Lashley KS. Patterns of cerebral integration indicated by the scotomas of migraine. Arch Neurol Psych. 1941;46:331-339.
  8. Leao AAP. Spreading depression of activity in cerebral cortex. Journal of Neurophysiology 1944;7:359-390.
  9. Leao AAP,  Morrison RS. Propagation of spreading cortical depression. Journal of Neurophysiology 1945;8:33-45.
  10. Leao AAP. Pial circulation and spreading depression of activity in the cerebral cortex. Journal of Neurophysiology 1944;7:391-396.
  11. Thomsen LL, Iversen HK, Olesen J. Cerebral blood flow velocities are reduced during attacks of unilateral migraine without aura. Cephalalgia 1995;15:109-16.
  12. Kobari M, Meyer JS, Ichijo M, Kawamura J. Cortical and subcortical hyperperfusion during migraine and cluster headache measured by Xe CT-CBF. Neuroradiology 1990;32:4-11.
  13. Sakai F,  Meyer JS. Regional cerebral hemodynamics during migraine and cluster headaches measured by the 133Xe inhalation method. Headache 1978;18:122-32.
  14. Tfelt-Hansen PC,  Koehler PJ. One hundred years of migraine research: major clinical and scientific observations from 1910 to 2010. Headache 2011;51:752-78.
  15. Moskowitz MA. Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 1993;43:S16-20.
  16. Thissen S, Vos IG, Schreuder TH, Schreurs WM, Postma LA, Koehler PJ. Persistent migraine aura: new cases, a literature review, and ideas about pathophysiology. Headache 2014;54:1290-309.
  17. Relja G, Granato A, Ukmar M, Ferretti G, Antonello RM, Zorzon M. Persistent aura without infarction: decription of the first case studied with both brain SPECT and perfusion MRI. Cephalalgia 2005;25:56-9.
  18. Chen WT, Lin YY, Fuh JL, Hamalainen MS, Ko YC, Wang SJ. Sustained visual cortex hyperexcitability in migraine with persistent visual aura. Brain 2011;134:2387-95.
  19. Wang YF, Fuh JL, Chen WT, Wang SJ. The visual aura rating scale as an outcome predictor for persistent visual aura without infarction. Cephalalgia 2008;28:1298-304.
  20. Chronicle E,  Mulleners W. Might migraine damage the brain? Cephalalgia 1994;14:415-8.
  21. Coppola G, Parisi V, Di Lorenzo C, et al. Lateral inhibition in visual cortex of migraine patients between attacks. J Headache Pain 2013;14:20,2377-14-20.
  22. Kruit MC, van Buchem MA, Launer LJ, Terwindt GM, Ferrari MD. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study. Cephalalgia 2010;30:129-36.
  23. Kruit MC, Launer LJ, Ferrari MD, van Buchem MA. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain 2005;128:2068-77.
  24. Tepper SJ, Tepper DE. The Cleveland Clinic Manual of Headache Therapy, 2nd ed. . Switzerland: Springer International Publishing, 2014.
  25. Kurth T, Bubes V, Buring J. Relative Contribution of Migraine with Aura to Cardiovascular Disease Occurrence in Women. Neurology 2013;80.
  26. Pezzini A, Del Zotto E, Giossi A, et al. The migraine-ischemic stroke relation in young adults. Stroke Res Treat 2010;2011:304921.
  27. Pezzini A, Del Zotto E, Giossi A, Volonghi I, Grassi M, Padovani A. The migraine-ischemic stroke connection: potential pathogenic mechanisms. Curr Mol Med 2009;9:215-26.
  28. Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol 2012;11:92-100.
  29. Kurth T. Migraine and ischaemic vascular events. Cephalalgia 2007;27:965-75.
  30. Tietjen EG. Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia 2007;27:981-7.
  31. Bousser MG,  Welch KM. Relation between migraine and stroke. Lancet Neurol 2005;4:533-42.

 

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Last updated on November 24th, 2020 at 04:46 pm

MEDICAL MARIJUANA (CANNABIS) FOR MIGRAINE, HEADACHE AND PAIN. A CRASH COURSE OF EVERYTHING YOU NEED TO KNOW.

@Neuralgroover

BACKGROUND

Medical marijuana (medical cannabis) for treatment of migraine, headache, pain, and chronic pain has become an increasingly hot topic of interest. As states continue to legalize the use of medical marijuana, there are increasing discussions and questions about its medical uses. What are the best medical marijuana strains for migraine, headache, and pain? Is medical marijuana helpful for migraine, chronic migraine, headache, pain, and chronic pain? How is medical marijuana used and dosed? Is medical marijuana legal to use? What are the side effects of medical marijuana? How do you get medical marijuana? How does marijuana differ from CBD (cannabidiol)? Patients ask about this type of treatment and many of these questions all the time, so this blog is to provide a comprehensive overview to answer all of these questions and much more. Reading the whole blog will give you a comprehensive, yet condensed detailed education of its history and everything you need to know about it, with an additional focus in the treatment of migraine and pain. Alternatively, you can skip down to find the specific topic that you are looking for information on.

When many people hear the term “medical marijuana”, they think of a street drug with no true medicinal qualities, used only for recreation and abuse. Their mind immediately activates the visual hippie imagery of the 1967 Summer of Love and 1969 Woodstock festival. However, this is an outdated view in the scientific research community. The term “marijuana” (sometimes spelled marihuana) is a loaded term with many negative connotations including old political and racial associations, and is associated with the plant being used recreationally as a drug of abuse. Cannabis is the scientific name of the plant and is the preferred terminology.

It is best to think of cannabis, as a broad class of medication. Within this medication class there are many types of cultivars (strains, breeds), or more accurately, chemovars (chemotypes). “Cultivar” is short for “cultivated variety”, while “chemovar” refers to “chemical variety”. The older cultivar classification system (Sativa, Indica, Ruderalis) has evolved to the more current, scientific, and simplified chemovar classification system. These systems are discussed in more detail further down under the treatment section.

Each chemovar has standardized reproducible compositions of cannabinoids and terpenes, which are the phytochemicals in cannabis that make up most of the medicinal qualities. The CBD and THC (tetrahydrocannabinol) cannabinoids and terpenes are discussed further down, and are also discussed in great detail here. Similar to a medication, there will be some variation in benefits, responses, effectiveness, and side effects between patients for each chemovar. Also similar to a medication, there are common characteristics attributed to each chemovar that the majority of users will experience.

For comparison of this concept, antidepressants are a broad class of medication. Within this medication class there are many types of drugs. Each drug has standardized reproducible compositions of neurotransmitter targets. Similarly, there will be some variation in benefits, responses, effectiveness, and side effects between patients for each drug, and a set of common characteristics attributed to each drug that the majority of users will experience.

 

HISTORY CRASH COURSE OF CANNABIS IN THE TREATMENT OF MIGRAINE, PROHIBITION, AND EVOLVING RETURN TO LEGAL STATUS

To understand the current legal status of cannabis, it is important to know the history of cannabis, detailed here. The use of cannabis for medicinal purposes dates back to ancient times, with a Western/Central Asian botanical origin. Medicinal uses have been documented to 4000 BC or more. Chinese physicians were using it for joint pains and analgesia in childbirth 5000 years ago. Fast forward to 1839 when Dr. William Brooke O’Shaughnessy introduced the Western world to the medicinal uses of Cannabis indica, or “Indian hemp”, after he spent a professorship in Calcutta, India and learned of its uses while there. He advocated for its use in analgesia and muscle relaxation.

Throughout the 1800s into the 1900s, it was being recommended by many prominent physicians of those times for numerous diseases, particularly pain, headache, chronic daily headache, migraine, and chronic migraine, and was being used both acutely and preventatively.

In 1890, Sir John Reynolds, President of the British Medical Association, and Physician to the Royal household, wrote a paper in Lancet on his 30 years of experience prescribing cannabis for variety of ailments, particularly migraine and neuralgia.

In 1915, the “Father of modern medicine”, Sir William Osler, was recommending cannabis for migraine treatment in his historic medical textbook of those times, The Principles and Practice of Medicine. He went on to suggest that when treating migraine, “Cannabis indica is probably the most satisfactory remedy. Seguin recommends a prolonged course.” Dr. E.C. Seguin whom he referenced was a well-known neurologist and was the President of the NY Neurological Society. He was a vocal proponent of cannabis for migraine.

Cannabis-based preparations had been listed in the US Dispensatory in 1845. In North America, some pharmaceutical companies including Bristol-Meyers Squib, Parke-Davis, and Eli Lilly were producing cannabis-based preparations, as was Burroughs-Wellcome & Co. in England.

In the 1930s, Harry Anslinger was leading the Federal Bureau of Narcotics, which was essentially the early DEA. He began a campaign against cannabis, attempting to associate psychosis, mental deterioration, addiction, and violent crimes to cannabis use. He claimed cannabis was a drug of abuse used by minority and low-income communities. Instead of using the term cannabis when he was pushing his prohibition bill in front of congress in 1937, he purposely would use the term “marijuana,” subtly trying to convey a racial connection since it was commonly associated with recreational use among poor Mexican immigrants who would bring it from Mexico to the USA at that time. He reportedly chose his terminology wisely to fit this agenda and distance the plant from the more scientific term cannabis along with its growing uses for medicinal and industrial purposes. Furthermore, marijuana has a general connotation of being used as an intoxicant and recreationally, whereas cannabis has more of a scientific association. For all of these reasons, cannabis should really be the preferred terminology over marijuana.

The Marihuana Tax Act of 1937 was passed, attributing large fines and prison time to anyone involved with cannabis. Some historians also discuss influence on this law from prominent businessmen such as Andrew Mellon and the DuPont family since the hemp industry was gaining traction in industrial uses, posing a threat to synthetic and other more common competitor products, but that is a whole different discussion. The AMA (American Medical Association) strongly opposed this law.

In 1938, Dr. Robert Walton argued against the new Marihuana Tax Act and published a comprehensive review of cannabis, referencing 12 experts on its effectiveness for migraine.

In 1941 cannabis preparations were taken off the US Pharmacopoeia and National Formulary.

In 1942, Dr. Fishbein, the Editor of JAMA (Journal of the American Medical Association), published his recommendations for oral preparations of cannabis over ergotamine for menstrual migraine. Other physicians also published supporting evidence for cannabis in migraine treatment.

Then the 1960s hit, where there was a resurgence of recreational marijuana use. This left a lasting and ongoing negative stigma of cannabis. Again, cue the visual hippie imagery of the 1967 Summer of Love and 1969 Woodstock festival. Unfortunately, many people who are not aware of cannabis history have been stuck in this mindset since…

The final nail in the coffin for legal cannabis use came with the Controlled Substances Act of 1970. This is what changed cannabis to its schedule 1 drug illegal status, of which it has remained since that time. The Assistant Secretary of Health, Dr. Roger O. Egeberg, stated his reason as follows, “Since there is still a considerable void in our knowledge of the plant and effects of the active drug contained in it, our recommendation is that marijuana be retained within schedule 1 at least until the completion of certain studies now underway to resolve the issue.”

Well, we are well past those studies Dr. Egeberg mentioned, and extensively more have been completed since then, yet cannabis remains federally illegal, despite all the evidence and vast amount of knowledge that we have gained from research. Thus, it is only a matter of time until the tide finally turns completely, and cannabis is rescheduled from Schedule 1 in my opinion.

So, cannabis has been a schedule 1 drug since 1970. Schedule 1 drugs also include heroin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (Ecstasy). According to the United States Drug Enforcement Agency (DEA), Schedule I drugs have a high potential for abuse, and have no accepted medical treatment use. If you are saying to yourself, that cannabis doesn’t seem like it fits into this category, you are certainly part of the majority opinion, which has shifted over the years. The DEA has continued to claim that cannabis has “no accepted medicinal use”, a statement which has no evidence to support it, but rather more evidence exists that disprove that claim.

Interestingly, despite this claim of no medicinal benefit, the US Government’s Department of Health and Human Services was awarded a patent (US Patent #6,630,507) for “cannabinoids as antioxidants and neuroprotectants” in 2003. Furthermore, the FDA has approved 3 synthetic versions of cannabinoids for medicinal purposes. Two are synthetic forms of THC (Dronabinol (Marinol), Nabilone (Cesamet)), and one is a purified form of CBD (Epidiolex). So, these statements and facts are clear contradictions to one another…

The schedule 1 classification has been a huge barrier preventing US federal funding for research and the legal ability to even proceed with research, although this has loosened up in recent years. This has historically been the primary hurdle in conducting medical research needed to obtain the evidence-based medicine in support of cannabis in the US. Meanwhile, many other countries such as Israel and Canada have been researching for years and have federal cannabis programs. For example, the Canadian equivalent to the US FDA is Health Canada. They have maintained a successful federal cannabis program for years. Despite this schedule 1 hurdle in the US, there has been accumulating evidence for various therapeutic benefits of cannabis, especially in the treatment of pain disorders.

In 1976, the FDA began an Investigational New Drug Program, after a glaucoma patient sued the government on grounds that cannabis was helping him, and won. This program closed in 1992, and 13 patients in the program at the time of closure were allowed to continue. Most recently, there were still 2 remaining who still receive monthly government supplied cannabis; one for multiple hereditary exostoses (painful bone tumor disorder), and the other for glaucoma. Access to this government supplied cannabis has since been controlled by the National Institute on Drug Abuse (NIDA), and the only federally approved cannabis source for decades has been from a farm at the University of Mississippi, who has had an ongoing contract with the federal government since 1968.

Through the 1990s-2000s, there was growing commentary from leading physicians and journals supporting cannabis for medicinal purposes. This has been accompanied by a growing push by medical organizations to reschedule cannabis to allow research and for patients who need it when they have failed all conventional treatments. Some of these organizations include American Academy of Neurology (AAN), American Medical Association (AMA), Epilepsy Foundation, American Journal of Public Health, and American Academy of Pediatrics (AAP).

In 2013, Dr. Sanjay Gupta MD, CNN Chief Medical Correspondent, issued a public apology article retracting his previous anti-marijuana stance which can be read here. He noted that “of more than 20,000 papers published in recent times, only 6% of the studies look at potential benefits of cannabis, while all the rest investigate potential harm, leading to an inherent bias and a profoundly distorted view.” He went on to further say:

“Well, I am here to apologize. I apologize because I didn’t look hard enough, until now. I didn’t look far enough. I didn’t review papers from smaller labs in other countries doing some remarkable research, and I was too dismissive of the loud chorus of legitimate patients whose symptoms improved on cannabis. Instead, I lumped them with the high-visibility malingerers, just looking to get high. I mistakenly believed the DEA listed marijuana as a Schedule 1 substance because of sound scientific proof. Surely, they must have quality reasoning as to why marijuana is in the category of the most dangerous drugs that have “no accepted medicinal use and a high potential for abuse.” They didn’t have the science to support that claim, and I now know that when it comes to marijuana neither of those things are true. It doesn’t have a high potential for abuse, and there are very legitimate medical applications. In fact, sometimes marijuana is the only thing that works. We have been terribly and systematically misled for nearly 70 years in the United States, and I apologize for my own role in that.”

Dr, Gupta has done a series of documentaries on CNN about the medicinal benefits of cannabis and are very enlightening to watch. This change in Dr. Gupta’s public opinion was also occurring along with spreading anecdotal cases of children with refractory pediatric epilepsy who were improving dramatically with CBD extracts from cannabis. One of these children, Charlotte Figi, became the poster child for this movement. In fact, the cannabis strain bred and extracted for high CBD for these purposes (Charlotte’s Web), was named after her. Unfortunately, she died 4/7/20 at the age of 13, and was remembered here.

The legal use of medicinal cannabis continues to increase globally, including the United States. In 1996, CA became the 1st state to pass the Compassionate Use Act, allowing the legal use of cannabis for medicinal purposes. Since that time, legalized cannabis has continued to grow. As of 11/4/20, medical use of cannabis is legal in 35 states (AK, AR, AZ, CA, CO, CT, DE, FL, HI, IL, LA, ME, MD, MA, MI, MN, MO, MS, MT, ND, NH, NJ, NM, NY, NV, OH, OK, OR, PA, RI, SD, UT, VT, WA, WV) + Washington DC. Recreational (“adult use”) is approved in 15 states (AK, AZ, CA, CO, IL, MA, ME, MI, MT, NJ, NV, OR, SD, VT, WA) + Washington DC. Despite a number of states legalizing cannabis use at the local level, it is still illegal federally in all states.

States which have medical cannabis programs have a list of qualifying conditions, which vary by state. The State Medical Board certifies doctors to “recommend” medical cannabis (Certificate to Recommend; CTR). The physician then confirms the qualifying condition and signs a “recommendation” form for potential benefit from medical cannabis. The patient then takes the recommendation to the local dispensary (which are also highly regulated by the state) and the patient discusses the best options there. However, it is important to remember that under the CSA (Controlled Substances Act), cannabis remains a schedule I drug, so doctors can’t “prescribe” cannabis. They can only “recommend” it. Also, interstate travel with any amount of cannabis or plant extract (including CBD products with THC content >0.3%) violates federal law and could potentially result in federal drug trafficking charges with stiff penalties of prison time and fines.

In 2009, the Justice Department sent a memorandum to federal prosecutors stating that patients and their providers should not face federal prosecution if they are following state law. In 2013 the Cole Memorandum was sent to US Attorney Generals, reinforcing that the Justice Department would not enforce federal prosecution in legal states who are following their state laws. In 2018, the Cole Memorandum was rescinded by Attorney General Jeff Sessions, which sent shockwaves through the industry. However, President Trump has continued to reinforce his support in protecting states that have legalized cannabis from federal prosecution. There have been discussions of re-evaluating the rescheduling of cannabis to remove the federal schedule 1 illegality, and it is suspected to be only a matter of time until this eventually happens.

 

MEDICAL CANNABIS USE FOR PAIN AND MIGRAINE

In medical cannabis registries, the most commonly reported reason for cannabis use is chronic pain of various types. Because of the increasing evidence of cannabis in the treatment of pain, the Canadian Pain Society revised their consensus statement in 2014 to recommend cannabinoids as a third-level therapy for chronic neuropathic (nerve) pain based on the abundance of supporting evidence and a NNT (number needed to treat) estimated at approximately 3 (the number of patients needed to treat for 1 of them to receive benefit). In 2017, The U.S. National Academies of Sciences, Engineering, and Medicine published a statement that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults. In February 2019, the World Health Organization (WHO) recommended that cannabis be rescheduled and removed from the most restrictive scheduling category.

Cannabis works through our endocannabinoid system. The endocannabinoid system is a normal and important biological system within everyone which helps to maintain homeostasis. It plays a role in many regulatory physiological processes across all organ systems, and is widely distributed throughout the central nervous system (brain and spinal cord) and peripheral nervous system (nerves outside of the spinal canal). This system is involved in the “runner’s high” as well. Notably, it plays a very strong role in pain pathways. This system works by the interaction of our own natural endocannabinoids turning on or turning off various endocannabinoid receptors throughout our body.

Over 540 phytochemicals have been described in cannabis, 18 different chemical classes, and more than 100 different phytocannabinoids. THC and CBD have been the most researched and are considered the major cannabinoids. There are many additional cannabinoids referred to as minor cannabinoids. The quantities of major and minor cannabinoids are widely variable between different types of cannabis chemovars. There is evidence for analgesic and anti-inflammatory effects in many of the cannabinoids. Cannabinoids are unique to the cannabis plant, and can be thought of as the “plant equivalents” of our own endocannabinoids. So, they interact with the same endocannabinoid receptors in our body as our own endocannabinoids do. The existing literature and research on the treatment of pain have primarily studied cannabis itself with its variable and often undefined combinations of THC, CBD, other cannabinoids, terpenes, and other constituents. These compounds, especially cannabinoids and terpenes, play significant roles in influencing one another and working together. The synergy and interactions between these compounds are referred to as the “cannabis entourage effects”. Thus, the medicinal benefits of cannabis are suspected to be from the “entourage effects”, more so than any of the individual components alone.

THC is a major cannabinoid and the most researched in cannabis. THC causes the psychoactive qualities (“high”) of cannabis. THC has been shown to be 20 times more anti-inflammatory than aspirin and 2 times as anti-inflammatory as hydrocortisone. It is also a potent anti-emetic (anti-nausea), which is why there are two FDA-approved synthetic THC medications for chemotherapy related nausea and vomiting (Dronabinol, Nabilone). THC is the cannabinoid which is tested for in drug tests. It is important to know that most CBD products contain trace amounts of THC, although there are some varieties that do not. It is typically a negligible amount unlikely to show up on a drug test, but it is not completely risk free. You can read about the different types of CBD products here. THC can be detected by a variety of ways, although most commonly it is tested in the urine. Here are the general timeframes that it will show positive:

  • Blood:
    • Few hours to 1-2 days after a single use
    • In heavy users (multiple times a day), possibly up to a week
  • Saliva:
    • Appears in saliva an hour after use, detectable for up to 1-2 days
  • Urine:
    • 5-12 days after one-time use
    • 11-18 days when used 2-4 days/week
    • 33-48 days when used 5-6 days/week
    • Around 50-65 days if used daily (stored in adipose tissue)
  • Hair:
    • Generally 90 days, but some hair follicle tests can go back years

CBD is the other major cannabinoid and has gained a lot of attention as a therapeutic agent over the past several years given a wide range of reported anecdotal benefits. It is discussed in much greater detail here. In contrast to THC, CBD is non-intoxicating (no “high”). Furthermore, it helps to neutralize some of the negative THC side effects. CBD has been shown to be several hundred more times anti-inflammatory than aspirin. Greater than 65 molecular receptor targets and greater than 80 mechanisms of action have been identified. There have been scientific, animal models, and very limited human clinical trials documenting its anti-inflammatory and analgesic (pain-relieving) properties. However, there are no high-quality research studies to date evaluating isolated pure CBD in any pain, migraine, or other headache disorders. So, it is unclear how much benefit CBD in isolation provides outside of the presumed entourage effects that it contributes to.

In November 2017, The World Health Organization (WHO) concluded that CBD exhibits no evidence for abuse or dependence potential, and that there is no evidence of public health related problems associated with its use. In January 2018, the World Anti-Doping Agency (WADA) removed CBD from their prohibited list, no longer banning use by athletes. In December 2018, the Agriculture Improvement Act (Farm Bill) was signed into law. This legalized the agricultural growth and use of hemp (cannabis strains containing 0.3% THC or less) and hemp derivatives such as CBD. The Farm Bill also removed hemp from the Controlled Substances Act, making it no longer an illegal substance under federal law. Up until the Farm Bill was passed, any form of cannabis or cannabis derivatives (including CBD) have been federally illegal since the Controlled Substance Act of 1970. Therefore, it is important to remember that cannabis chemovars and CBD oils with greater than 0.3% THC are still illegal federally, require a medical cannabis card for use, and are illegal to cross state lines with. In May 2019, TSA began to allow travel with CBD products containing 0.3% or less of THC.

The terpenes account for many of the pharmacological properties of cannabis, as well as many medicinal herbs, plants and essential oils. They are the source of flavors, aromas, and other characteristics that help differentiate cannabis cultivars. Terpenes are often used in many household products such as limonene (citrus), pinene (pine, conifer), and linalool (lavender) to name just a few. Similar to the cannabinoids, many have anti-inflammatory and analgesic properties.

 

SO WHAT TYPES OF CANNABIS ARE THERE AND HOW DO I KNOW WHICH ONE TO USE?

As discussed at the beginning of the blog above, there are many types of cannabis chemovars that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and chemovar characteristics. Different chemovars have different ratios of these compounds, and thus have different characteristics.

The older cultivar (strain, breed) classification system was based on strain appearance, smell, and clinical effects. Cannabis Sativa strains were generally described by patients as uplifting, energetic, creative, euphoria, spacey, cerebrally-focused effects, and better for day use, while cannabis Indica strains were typically described as calming, relaxing, sedative, full body effects such as “body buzz”, and better for night use. Cannabis ruderalis (hemp) strains were considered predominantly or purely high CBD without any real clinical use effects.

However, biochemical studies of specific strain names often do not accurately distinguish CBD and THC content, which was the predominant basis for strain classification. Strain characteristics and clinical effects are dependent on varying ratios of major and minor cannabinoids and terpenes, not only from CBD:THC ratios, as there are no significant differences in CBD:THC ratios between many Sativa and Indica strains when studied chemically. Most strains used today are hybrid strains genetically cross-bred for standardized CBD, THC, terpenes, and minor cannabinoid content.

The older cultivar classification system has evolved to the newer and more scientific chemovar (chemotype) classification system, and is divided into type I-III chemovars. This system allows medical users to find a chemical profile better matching their pharmacological needs.

Type I chemovars are THC predominant. They are high THC (>0.3%, but generally >10-20%), and low CBD (<0.5%, but generally <2%). They are very intoxicating, and associated with recreational more than medical use. They are moderately-heavily psychedelic with changes in perception and sensory awareness and have the potential for significant physiological changes in heart rate and blood pressure. They can intensify relief from symptoms like nausea or pain, so terminal cancer patients may be one of the few true medical uses for these chemovars.

Type II chemovars are more balanced THC and CBD. They are high THC (>0.3%, but generally 3%-10%), and high CBD (>0.5%, but generally 1%- 14%). They are intoxicating to a lesser degree than Type I chemovars. They can be mildly-moderately psychedelic with milder cerebral and cognitive changes in perception and sensory awareness possible. In general, they can be more effective at treating symptoms with less negative side effects.

Type III chemovars are CBD predominant. They are low THC (<0.3%, but generally 0%-1%), and high CBD (>0.5%, but generally 5%-20% or more). They have low to no intoxication side effects. There is little to no cognitive impairment for most, but there can be possible mild effects in sensitive users, depending on the THC content.

 

WHAT IS THE EVIDENCE FOR CANNABIS AND MIGRAINE?

                  The benefits of cannabis/cannabinoids in various chronic pain disorders has been well established. These benefits are suspected to likely extrapolate to headache disorders including migraine given overlapping neurobiological pathways of pain. There are some notable interactions and synergies between the cannabinoid receptors and pathways of migraine involving the trigeminovascular system (including the same receptors that the triptans work on) and serotonergic system. A more detailed discussion of this physiology can be read here and here. The medical literature regarding treatment of headache, migraine, and facial pain disorders shows limited supporting evidence for cannabis/cannabinoids in the treatment of chronic headaches, migraine including chronic migraine, medication overuse headache, cluster headache, idiopathic intracranial hypertension, and multiple sclerosis (MS) associated trigeminal neuralgia. However, the majority of this limited supporting evidence consists primarily of case series, case studies, case reports, surveys, clinical/anecdotal reports, and one retrospective analysis. There have been no placebo-controlled studies of cannabis for headache disorders or migraine thus far. There are only two prospective trials containing a control group evaluating the use of cannabinoids in the treatment of headache disorders, both of which showed benefit. The details and references of these studies and all of the smaller case studies mentioned can be read here and here.

Part of the difficulty in these types of trials, besides the federal illegality and the schedule 1 status of cannabis, is that there are so many variations of chemovars. It is unknown what chemovars and varieties of cannabis might be most helpful for migraine treatment. Most likely, it is not a one size fits all. Similar to how patients have a wide variety of therapeutic responses to abortive and preventive migraine treatments (what works for one person often does not work for another, etc.), responses to chemovars is probably similar. One person may respond very well to a specific chemovar, while another may respond better to a different one. Everyone is different, so like the trial and error process of trying different medications to see which may work best, cannabis chemovars most likely have a similar process.

With that said, there have been a couple studies evaluating a large medical cannabis registry, in an attempt to determine what chemovars patients with migraine and headache prefer to use. In one study, which can be read here, chemovars with high THC and low CBD were most preferred. “OG Shark” was the most preferred chemovar and consisted of high THC/THCA (tetrahydrocannabinolic acid) and low CBD/CBDA (cannabidiolic acid), with predominant terpenes β-caryophyllene and β-myrcene. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Notably in that study, many headache patients replaced pharmaceuticals with cannabis, most commonly opiates/opioids (43.4% in headache patients, and up to 73% in chronic pain patients), anti-depressant/anti-anxiety (39%), NSAIDs (21%), triptans (8.1%), anticonvulsants (7.7%), muscle relaxers (7%), and ergots (0.4%).

In a follow up study (publication pending) 6 of the top 8 preferred chemovars were again high THC/low CBD, with “Headband” (22-24% THC, <1% CBD), “Warlock CBD” (8-11% THC, 8-11% CBD), and “Master Kush” (24-26% THC, <1% CBD) all tied for the top preferred cannabis chemovar. All three of these chemovars again had β-caryophyllene as one of their top 3 predominant terpenes, along with a mix of linalool, limonene, β-myrcene, bisabolol, and humulene as one of the top 3 predominant terpenes between them. There were 2 preferred chemovars which had high CBD and lower THC. They were “Warlock CBD” (8-11% THC, 8-11% CBD) which was in a 3-way tie for top preferred chemovar as mentioned above, and “Cannatonic” (3-7% THC, 6-10% CBD).

 

GENERAL USE GUIDELINES AND SUGGESTIONS

Cannabis can be used by smoked, vaporized, oral, oral-mucosal, topical, or rectal routes of administration. Oral routes cause a slower onset of action and a prolonged duration of action. Smoking and vaporizing cause the fastest onset of action and the shortest duration of action. Smoking is not recommended due to the production of unhealthy respiratory irritants and toxins. Vaporizing is a newer technique with a goal of suppressing irritating respiratory toxins by heating cannabis to a temperature where active cannabinoid vapors form, but below the point of combustion where smoke and associated respiratory toxins are produced.

Start low on the dose, go slow, and stay on as low of a dose as possible. This promotes tolerance to the THC psychoactive effects. Use the lowest dose THC possible, and use CBD and THC together because CBD helps to neutralize some of the negative THC side effects. Approximately 15-20% CBD with less than 1% THC is a good starting point to consider. CBD predominant preparations are better for working and daytime use, while THC predominant preparations are better for after work and at bedtime. Long acting oral formulations are better for chronic conditions and symptoms. Vaporization can be an as needed (prn) for episodic symptom exacerbations. Driving should be avoided for at least 4 hours after inhaled cannabis, 6 hours after ingested cannabis, and 8 hours if euphoria is experienced.

Common dosing quantities and terminology include one joint = 0.3-0.5 grams, one eighth = 3.5 grams, one quarter = 7 grams, and one ounce = 28 grams. Based on peer-reviewed literature, the majority of patients using smoked or orally ingested cannabis for medical purposes have been observed to use between approximately 10-20 grams of cannabis per week, 1-3 grams per day, and a frequency of 3-4 times daily. With that said, specific dosing recommendations are not available, and this is one area of much needed research in order to determine the best dosing for various disorders.

For THC dosing, 1-2.5 mg is a good starting dose. For example, starting at bedtime and increase 1-2.5 mg every few days at bedtime or daytime (depending on treatment goals) until benefits or side effects are reached. At 5 mg THC, many will experience benefit without excess side-effects. At 10 mg, most will have side effects. At 15 mg or more it may cause psychiatric side effects. As a loose reference, a 0.5-1 g cannabis cigarette may contain approximately 0.2-4.4 mg THC. However, THC content has gotten much higher in many chemovars over the years, so this can be much higher. The total daily THC dose should be less than 20-30 mg to limit adverse effects and tolerance. In addition, THC should preferably be used with CBD as mentioned above. Use of high dose THC chemovars more than 5 grams per day of flower suggests possible tolerance or misuse, and is usually unjustified medically unless perhaps an end stage cancer patient.

For CBD Dosing, starting at 5-20 mg/day divided once to three times daily, and titrating to effect is suggested. It is suspected that high doses are likely needed for pain and inflammation disorders, but this needs to be clarified with research. There are no established dosing guidelines or max doses established. For reference, doses of 400-600 mg/day showed benefit in anxiety, doses of 600-800 mg/day showed benefit in psychosis, and doses up to 2500 mg/day (25-50 mg/kg) have been used in epilepsy studies.

 

SIDE EFFECTS AND ADVERSE REACTIONS

Side effects are influenced by dose, method of administration, patient tolerance, chemovar of cannabis, ratios of THC to CBD, cannabinoids, terpenes, production quality control (toxins, fungus, bacteria, heavy metals, etc.) to name a few. Many studies have been inconclusive or contradictory in terms of association with stroke, heart attack. This publication provides the most comprehensive review of cannabis and its recognized side effects. The most common side effects (which vary depending on the chemovar) include dizziness, dry mouth, increased appetite, disturbances in concentration, and sedation/drowsiness. Less common side effects can include incoordination, euphoria, anxiety, and paranoid thinking. In the majority of trials, side effects have been well tolerated, mild to moderate, transient, and not bothersome enough that many patients withdrew from studies. Overdose can occur and is typically from high THC content and oral dosing. Signs may include tachycardia, arrhythmia, confusion, panic attack, extreme paranoia, and hallucinations.

From existing research, there is concern for possible long-term cognitive side effects of cannabis use during adolescent years when the brain is still rewiring, pruning, and organizing itself. Studies suggest a decline in IQ/neurocognitive function when used frequently under age 18. In adults, a larger study suggested problems in verbal memory recall after chronic cumulative use (after 5 years of cumulative frequent/chronic use, 1 in 2 people may recall 1 word less from a list of 15 words). Current users had both decreased verbal memory and processing speed.

According to “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research”, published by the National Academies of Sciences, Engineering, and Medicine in January 2017, the following are conclusions regarding cannabis side effects based on existing literature reviews.

For cardiovascular risk, there is limited evidence of cannabis triggering an acute MI (heart attack), ischemic stroke, or subarachnoid hemorrhage. There is no evidence to support or refute chronic cannabis use and increased risk of acute MI.

For cancer risk, there is moderate evidence of no association between the incidence of lung cancer (cannabis smoking), or the incidence of head and neck cancers. There is no or insufficient evidence to support associations with other cancers.

For respiratory disease risk, there is substantial evidence for worse respiratory symptoms and more frequent chronic bronchitis episodes (long-term cannabis smoking).

For neurocognitive risk, there is moderate evidence of impairment in the cognitive domains of learning, memory, and attention with acute cannabis use, but limited evidence for persistent impairments in cognitive domains of learning, memory, and attention after sustained cannabis abstinence.

For mental health risk, there is substantial evidence for development of schizophrenia or other psychoses in those at risk genetically, with the highest risk among the most frequent users. There is moderate evidence for increased symptoms of mania and hypomania in bipolar disorder. There is a small increased risk of depressive disorders and an increased incidence of social anxiety disorder. There is an increased incidence of suicidal ideation and suicide attempts with higher incidence in heavier users, and an increased incidence of suicide completion.

For prenatal, perinatal, and neonatal exposure, there is substantial evidence between maternal cannabis smoking and lower birth weight. During lactation, the amount reaching the infant is very low, although the effects of this are unknown. Therefore, it is recommended to not use cannabis in either pregnancy or breastfeeding.

There is substantial evidence for an increased risk of motor vehicle crashes. There is moderate evidence for increased risk of overdose, especially among pediatric populations. There is no or insufficient evidence for all-cause mortality, and there has been no documented death exclusively attributed to cannabis overdose or use. Cannabis has been shown in toxicology studies to be 114 times less lethal than alcohol. In fact, the deadliest substances in one toxicology study in order were alcohol, heroin, cocaine, tobacco, ecstasy, methamphetamine, and lastly, cannabis.

 

CANNABIS HYPEREMESIS SYNDROME

Cannabis hyperemesis syndrome (CHS) has become increasingly seen as states legalize cannabis. It presents with clinical symptoms of cyclical nausea/vomiting, diffuse abdominal pain, and the need to take frequent hot showers (this is a pathognomonic sign).

Episodes of these symptoms last 24-48 hours, may last 7-10 days, and often recur with re-exposure of cannabis. CHS tends to be associated with high-dose, high-THC regular cannabis use. It can be confused with CVS (cyclical vomiting syndrome), and is differentiated by a history of chronic cannabis use and frequent hot bathing which produces temporary relief. The etiology (cause) of CHS is not fully understood. It has been theorized that there is a dysregulation of the endogenous cannabinoid system by downregulation of CB1 (cannabinoid 1) receptors, and in the GI (gastrointestinal) tract this may slow gastric motility, causing hyperemesis. Genetic differences in the cytochrome P450 system (enzymes in the liver which metabolize drugs) has also been proposed. The TRPV1 receptor in our bodies interacts with the endocannabinoid system. More specifically, anandamide (our main natural endocannabinoid) works at this receptor (one of many). Interestingly, this receptor is also the capsaicin receptor, and is activated by heat such as in hot peppers (which contain capsaicin). Therefore, it has also been proposed that perhaps the fact that these patients take frequent hot showers/baths for relief is because they are indirectly activating their endocannabinoid system.

Treatment of CHS revolves around cannabis cessation. There is no way around it. Supportive therapy can assist with fluid resuscitation. Capsaicin 0.075% topically to areas of the abdomen, back of arms, and areas that hot water gives symptom relief have shown some benefit (not using on private areas or mucosal surfaces). Antipsychotics such as Haloperidol and Olanzapine showed some temporary benefit. Conventional antiemetics, antihistamines, serotonin antagonists, benzodiazepines have shown limited evidence for effectiveness, and opiates should be avoided.

 

ADDICTION AND ABUSE

Comparative addiction rates between substances have included tobacco 32%, heroin 23%, cocaine 17%, alcohol 15%, and lastly cannabis 9% (but 17% when used in adolescence, and 25-50% in adolescents who are using daily). Tolerance develops much faster with high potency high THC chemovars.

The DSM-5 recognizes 5 cannabis-associated disorders:

-Cannabis Use Disorder

-Cannabis Intoxication

-Cannabis Withdrawal

-Other Cannabis-Induced Disorders (Cannabis Intoxication Delirium, Cannabis Induced Psychotic Disorder, Cannabis Induced Anxiety Disorder, Cannabis Induced Sleep Disorder

-Unspecified Cannabis-Related Disorder

An estimated 3-4% of users meet criteria for Cannabis Use Disorder. The prevalence decreases with age, with the highest ages 18-29 years old (4.4%), and lowest ages 65 and older (0.01%). Cannabis Use Disorder is divided into mild (2-3 criteria), moderate (4-6 criteria), and severe (7 or more criteria). These criteria include any of the following:

  • Cravings and urges to use cannabis
  • Failure to fulfill major role obligations (work, school or home)
  • Unsuccessful attempts to quit/cut down
  • Spends excessive time in acquisition, using or recovering from use
  • Using Cannabis in larger amounts or for longer than you meant to (tolerance)
  • Continued use despite consistent social or interpersonal problems
  • Recurrent use in hazardous situations
  • Important social, occupational, or recreational activities are given up or reduced because of cannabis use
  • Needing more cannabis to get the effect you want (Tolerance)
  • Uses despite negative effects (physical or psychological)
  • Development of withdrawal symptoms, which can be relieved by taking more of the substance

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

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Last updated on November 24th, 2020 at 04:46 pm

MENSTRUAL MIGRAINE TREATMENT TIPS AND CONTRACEPTION STROKE RISK.

@Neuralgroover

BACKGROUND

Menstrual migraine is very common, and one of many forms of migraine. Overall, migraine is estimated to effect about 18% of women and 6% of men. That is a 3:1 ratio. Much of that uneven ratio is due to the hormonal influence of migraine in women, particularly estrogen. Even more specifically, it is the drop in estrogen during the menstrual cycle which is the most common culprit for menstrual migraine (migraines during menses and outside of menses) and menstrual migraine (migraines during menses only).

Let’s first talk about some basic oral contraceptive facts. Estrogen and progestin are the components in combination oral contraceptives (COC). In most COCs, the estrogen is ethinyl estradiol (some older ones use mestranol). Most COCs nowadays are low dose COCs (35 mcg (micrograms) or less of ethinyl estradiol), which has less risk of thromboembolic (blood clot) events.

Combined hormonal contraception (CHC) also come as patches (Ortho Evra) and vaginal rings (Nuvaring). Patch users may be exposed to 60% more estrogen than in a 35 mcg ethinyl estradiol oral contraceptive, levels may not remain steady and peak values may be lower. The vaginal ring delivers 15 mcg ethinyl estradiol and 120 mcg etonogestrel, and is replaced every 4 weeks.

Contraceptive doses of hormones suppress ovarian function, prevent ovulation and pregnancy, and often provide “supraphysiologic” doses of hormones.

Hormonal therapy (such as ethinyl estradiol 20 mcg): do not suppress ovarian function, do not prevent pregnancy, and are for more physiologic doses. They are meant as estrogen replacement. Endogenous ovarian hormonal production is typically still occurring.

 

CONTRACEPTION ADJUSTMENT HACKS TO LESSEN MENSTRUAL MIGRAINE

Most menstrual migraines occur in association with the drop in estrogen during the menstrual cycle. This occurs just prior to ovulation, at the end of the luteal phase if pregnancy does not occur, and during the placebo pill of oral contraceptives. It is recommended to use a monophasic pill containing 35 mcg or less of ethinyl estradiol (20-35 mcg of ethinyl estradiol is typical for most common formulations). Some data suggest 20 mcg pills may not sufficiently suppress ovulation. For women over 160 lbs, the 35 mcg ethinyl estradiol pills will be more protective than those with less than 35 mcg.

Here are a few options (certainly not an all-inclusive list) to discuss with your doctor to try to decrease menstrual migraine with combined hormonal contraception adjustments if you are using oral contraceptives:

 

1) Continuous extended release contraception:

-Cycle off to have withdrawal bleeding only as needed. Most commonly this is done every 3 months.

-Seasonale (levonorgestrel 150 mcg, ethinyl estradiol 30 mcg): 12 weeks of active contraceptive pill, followed by 1 week of placebo. This essentially results in 4 yearly menstrual cycles.

-Lybrel (levonorgestrel 90 mcg, ethinyl estradiol 20 mcg): active contraceptive pill taken continuously with no placebo intervals.

 

2) Add-back estrogen the week of placebo to minimize drop in estradiol:

-Mircette (desogestrel 150 mcg, ethinyl estradiol): 3 weeks of 20 mcg ethinyl estradiol; 2 days placebo; 5 days of 10 mcg ethinyl estradiol.

-Seasonique: Continuous extended-release oral contraceptive pill of 30 mcg ethinyl estradiol for 12 weeks followed by 1 week of low dose ethinyl estradiol 10 mcg.

-Ethinyl estradiol 10 mcg patch during placebo week.

 

3) Extended dosing regimens:

-Yaz (drospirenone 3000 mcg, ethinyl estradiol 20 mcg): 24 active oral contraceptive pills followed by 4 days placebo.

-Loestrin 24 (norethindrone 1000 mcg, ethinyl estradiol 20 mccg): 24 active oral contraceptive pills followed by 4 days placebo.

 

STROKE RISK AND RECOMMENDATIONS FOR ORAL CONTRACEPTION IN MIGRAINE

Women younger than age 45 who have migraine with aura, have a 2 fold increased risk of stroke, although this risk is still very low. This risk increases to 6 fold in the setting of oral contraceptive use containing estrogen, and rockets to more than 9 fold with combined smoking and oral contraceptive use. So, if you have migraine with aura, you can absolutely NOT be a smoker and use estrogen containing contraception, especially if you are under age 45!!! Women who are smokers and have migraine with aura should consider estrogen containing oral contraception a contraindication. You can read about migraine aura here. Notably, migraine without aura does not appear to have the same increased risk.

Oral contraceptive use in non-smoking women with migraine with aura is more controversial. The World Health Organization (WHO) and American College of Obstetrics and Gynecology (ACOG) suggest that in non-smoking women under age 35 with migraine with aura, there is an acceptable low risk of oral contraceptive use. However, in women over age 35, the risk is unacceptably higher and oral contraceptive use is contraindicated. According to the International Headache Society (IHS), in non-smoking women with migraine with aura who are either younger or older than age 35, taking into account other cardiovascular (heart disease) and cerebrovascular (stroke) risk factors should  individualize the decision for oral contraceptives with weighing the risks vs. benefits. These risks would include ischemic heart disease, family history of early heart disease at a young age of less than 45 years old, heart disease with concern for emboli such as atrial fibrillation, uncontrolled hypertension, hyperlipidemia, diabetes, obesity, systemic disease associated with increased stroke (connective tissue disease, sickle cell, hypercoagulability (blood clots)), etc. In women with an increased risk of stroke, and especially with multiple vascular risk factors, non-estrogen methods of birth control such as progesterone-only forms of contraception are recommended.

It is also suggested to avoid in women (and men) with prolonged migraine aura (greater than 60 minutes), migraine with focal neurologic symptoms (such as hemiplegic migraine), and basilar migraine (now known as migraine with brainstem aura).

The bottom line is if you have typical migraine with aura without any atypical features (for example, aura does not extend more than 60 minutes), are not a smoker, and do not have cardiovascular or cerebrovascular risk factors as mentioned above, estrogen containing contraceptives are not an absolute contraindication. However, you and your doctor should ultimately decide whether the benefits outweigh the risks. If these medications are used, the recommendation is to use the lowest dose possible, 35 mcg or less. Higher doses of estrogen have quite clearly been associated with increased stroke risk (many earlier studies showing this connection were done with higher doses such as 50 mcg or more). Migraine associated stroke (migrainous infarction)  is also discussed here. On the other hand, if you have migraine with aura, are under age 45, and are a smoker, the recommendation would be to avoid any estrogen containing contraception. Lastly, there doesn’t seem to be an increased risk with a progesterone-based pill. So, this is an alternative option to consider if you cannot use estrogen-based contraception, along with the many other non-estrogen options you can discuss with your gynecologist.

 

“MINI-PROPHYLAXIS” HACKS DURING THE MENSTRUAL CYCLE

Lastly, here are a few tricks (but certainly not an all-inclusive list) often used only during the menstrual cycle (after discussing with your doctor) to try to decrease migraine frequency. These are called “mini-prophylaxis” strategies since these medications are used daily, but only around the menstrual cycle, as opposed to a daily continuous preventive medication taken for months at a time (which is always a good option too). The goals of these strategies is use medications that have a longer duration of action (last longer) in hopes of preventing migraine recurrence/return within 24 hours, typical of menstrual migraine, and to target the long duration (often multiple days) commonly seen with menstrual migraines:

 

Naratriptan (Amerge) 1.25 mg twice daily (half of a 2.5 mg tablet) beginning 1-2 days before expected onset of menstrual migraine, and maintained for several days through period. In addition, you may use Naratriptan 2.5 mg for breakthrough migraines, but no more than once daily (2 total doses per 24 hours).

 

Frovatriptan (Frova) 1.25 mg twice daily (half of a 2.5 mg tablet) beginning 1-2 days before expected onset of menstrual migraine, and maintained for several days through period. In addition, you may use Frovatriptan 2.5 mg for breakthrough migraines, but no more than once daily (2 total doses per 24 hours).

 

Naproxen Sodium (Anaprox) 550 mg twice daily beginning 2 days before expected onset of menstrual migraine, and maintained through period. Take with food. In addition, you may use your triptan at earliest sign of breakthrough migraines and may repeat once in 2 hours if needed.

 

Methergine (Methylergonovine) 0.2 mg three to four times daily beginning 2 days before expected onset of menstrual migraine and continuing through cycle.

 

DHE Nasal Spray (Migranal): 1 spray in each nostril by pointing away from face and not sniffing. Then, repeat one spray in each nostril in 15 minutes for a total of 4 sprays per dose. Repeat this dosing twice daily beginning 2 days before expected onset of menstrual migraine, and continue through period.

 

Cafergot (Ergotamine 1 mg/Caffeine 100 mg): 2 tablets at migraine onset, followed by 1 tablet every half hour until relief occurs. Do not take more than 6 tablets per headache attack or 10 tablets in a 7-day period.

 

Ergomar (Ergotamine): 2 mg sublingually followed by 1-2 mg every half hour until relief occurs. Do not exceed 6 mg per day and no more than 10 mg per week.

 

Rizatriptan (Maxalt) 10 mg + Dexamethasone 4 mg at menstrual migraine onset.

 

Nurtec ODT (Rimegepant) 75 mg starting 1-2 days before start of menstrual migraine and continue once daily for a few days during menses. There is no evidence for this currently and it is not commonly done, but given that Nurtec ODT seems to provide relief for 48 hours with a single dose, it could be worth trying given the long duration and high 24 hour recurrence typically seen in menstrual migraine. Ubrelvy (Ubrogepant) could be another consideration.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

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Last updated on November 24th, 2020 at 04:47 pm

SUPPLEMENTS, NATURAL TREATMENTS, VITAMINS, AND NUTRACEUTICALS FOR MIGRAINE PREVENTION, AND WHICH ARE BEST FOR YOU.

@Neuralgroover

 

Worldwide, migraine affects more than 10-12% of the population, with approximately 700 million migraineurs estimated worldwide.1 It is estimated that there are 38 million migraineurs in the US, accounting for 12% of the US population. Migraine affects 18% of women and 6% of men2,3. Nearly 25% of U.S. households include someone with migraine.

 

In 2016, migraine was determined to be the 2nd leading cause of all global disability, and the 2nd leading cause of all neurological disease burden4. Migraine accounts for 50% of all neurologic disability. Furthermore, chronic pain in general is the largest contributor to years lived with disability globally5, and is associated with tremendous negative impacts on social, economic, and personal function.

 

In addition to the attack-related disability, many sufferers live in fear because their migraines disrupt their ability to work, go to school, partake in social activities, or care for their families, and this significantly limits their overall quality of life. More than 90% of migraine sufferers are unable to work or function normally during their attacks. American employers lose more than $20 billion each year as a result of 113 million lost workdays due to migraine.6

 

Migraine treatment is divided into acute and preventive (prophylactic) therapy. Most existing preventive therapies are adopted from anti-epileptic, antidepressant, and antihypertensive medications. However, many of these medications are not well tolerated, resulting in poor compliance. Adherence to oral migraine preventative medication is around 26% at 6 months and declines to 17% at one year.7 This is often due to intolerable side effects. Many patients, due to lack of efficacy of preventative treatments, often resort to overuse of acute medications. This results in additional decline in quality of life and economic burden.8 Onabotulinumtoxin-A is currently the only FDA-approved treatment available for chronic migraine. However, most patients must fail at least three preventative treatments prior to receiving Onabotulinumtoxin-A. As such, Onabotulinumtoxin-A is typically a fourth line option for the prevention of chronic migraine. In addition, it is not approved for patients who have episodic migraine. There are 4 calcitonin gene related peptide (CGRP) monoclonal antibody antagonists that have been approved for the prevention of migraine.  There also exists a limited number of neuromodulatory devices. Lack of insurance coverage of these devices precludes their routine use in clinical practice.  This confers a large unmet need for additional preventive migraine treatments and additional therapeutic targets.

 

Migraine prevention is a key aspect to maintaining a good quality of life.  Abnormal neuronal membrane ion channels, low ionized magnesium levels, increased excitatory glutamatergic activity, and mitochondrial dysfunction with abnormal energy metabolism are associated with migraine. The goal of nutraceuticals is to target these factors in order to improve energy metabolism and reduce neuronal hyperexcitability in the brain. Patients often seek complementary and alternative medicine (CAM) for prevention of their headaches after finding standard prescription treatments intolerable due to side effects, or just ineffective. Many patients feel that “natural” substances are less toxic than prescription medications. Thus, the nutraceutical and herbal supplement industry is a multibillion-dollar industry. CAMs include, but are not limited to, nutraceuticals (vitamins and supplements such as magnesium, coenzyme Q10 (CoQ10), vitamin B2 (riboflavin), alpha lipoic acid, vitamin D, 5-HTP, fish oil, melatonin), and herbal preparations (butterbur, feverfew, ginger, and cannabidiol).

 

The use of CAMs has been significantly rising in the US and Europe9–12, and is becoming more evident especially in patients with migraine and other headache disorders. In a recent questionnaire-based survey in Germany and Austria, 81.7% of patients seen in tertiary outpatient headache clinics reported use of CAM13.  There are a multitude of different migraine related supplements on the market with variable combinations or sold separately as the individual components. Below, we discuss the most commonly used and studied supplements for migraine prevention.

 

VITAMINS and SUPPLEMENTS:

  1. Magnesium

Magnesium has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 It is also rated highly and recommended by the Canadian Headache Society.15 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. More than 325 enzymes are magnesium dependent, many of which are brain enzymes. Magnesium is involved in all reactions that involve the formation and utilization of adenosine-5′-triphosphate (ATP) in energy metabolism16–19. Proper magnesium levels are known to help normalize blood pressure, have anticoagulant, anti-platelet aggregating effects, regulate cell proliferation, protein synthesis, cellular energy and cell membrane stability, as well as blood sugar levels19–21. Studies have shown low levels of brain magnesium22,23 may be a contributor to migraine pathophysiology. Magnesium influences multiple steps in the current understanding of migraine pathophysiology including cortical spreading depression, serotonin receptor activity, neurotransmitter release, interference with inflammatory mediators, nitric oxide production, platelet aggregation, vascular tone, NMDA receptor interaction, production and release of substance P which activates pain fibers24–31. Magnesium is a mineral that functions as a coenzyme for various neurologic functions and other physiologic mechanisms.    According to two double-blind studies, high-dose oral magnesium supplementation appears to be effective in migraine prophylaxis. Trials have shown that magnesium supplementation is very effective in migraine treatment, with migraine attack reductions of up to 42%.32–37 Other studies have also shown benefit in migraine prevention when combined with coenzyme Q10 and feverfew as well.38 Magnesium (250 mg twice a day or 500 mg at bed) has a relaxant effect on smooth muscles such as blood vessels. We often give intravenous magnesium to patients who come into the emergency department for migraine because it helps to break the migraine. Three trials found 40-90% average headache reduction when used as a preventative. Magnesium also demonstrated the benefit in menstrually related migraine. Magnesium is part of the messenger system in the serotonin cascade and it is a good muscle relaxant. Some forms can be useful for constipation which can be a side effect of other medications used to treat migraine. Good sources include nuts, whole grains, and tomatoes.

 

There are different forms of magnesium, and we’ll discuss the most common types. Magnesium types can be tailored to patient characteristics as follows.39 Magnesium glycinate is a good choice for those with a sensitive stomach who have gastrointestinal side effects such as diarrhea with other forms of magnesium. It is anecdotally also helpful with anxiety and sleep. Magnesium threonate also has low risk of gastrointestinal side effects and anecdotally helpful with cognitive function and brain fog symptoms. Magnesium malate has low gastrointestinal side effects and is reportedly more energizing and anecdotally often helpful in fibromyalgia and chronic fatigue syndrome. Magnesium citrate is one of the most studied, popular, and well-absorbed forms of magnesium. It can also be mixed easily with liquids if you can’t take pills. However, it comes with a higher risk of diarrhea and gastrointestinal side effects, although this could be helpful for those with constipation. Magnesium oxide is also well studied, cheap, and often used for heartburn and indigestion. However, it is not well absorbed and can have some laxative side effects as well, so can also be helpful for constipation.

 

Dosing should generally be somewhere between 400-800 mg daily. It should preferably contain 24 mmol (600 mg) of elemental magnesium daily as magnesium citrate​ based on trials that showed benefit with this specific one more than others, and this is the recommendation of the Canadian Headache Society.15 If this type is not tolerated, other forms of magnesium as discussed above are certainly acceptable.

 

  1. Vitamin D3 (Cholecalciferol)

Vitamin D deficiency is a worldwide problem. Vitamin D is not actually a vitamin, but a hormone that the body makes from a type of cholesterol in the skin when it is exposed to UVB radiation from the sun. Small amounts also come from diet. It has anti-inflammatory activities, analgesic effects, may reduce nitric oxide and assists in magnesium and calcium absorption. Deficiency is suspected to play a role in mechanisms responsible for migraine and other pain syndromes, and vitamin D levels have been shown to be low in chronic migraineurs40. The best form is vitamin D3 (cholecalciferol) anywhere from 1,000 to 4,000 IU daily.

 

  1. 5-HTP (5-Hydroxytryptophan)

This is an amino acid that is made by the body from tryptophan (amino acid you get from your diet), and is involved in mood, sleep, and pain regulation. 5-HTP is typically produced from the seeds of the Griffonia simplicifolia plant. 5-HTP is converted into serotonin (5-hydroxytryptamine), an important brain neurotransmitter involved in migraine pathways and other neurologic pathways. 5-HTP is also converted into melatonin which aids in sleep, as well as dopamine, another important neurotransmitter. The effects of 5-HTP are felt to be similar to the antidepressants that are thought to increase the amount of serotonin available to the brain, and thus a mood enhancing chemical. Some studies have suggested that 5-HTP was as effective as some prescription migraine medications such as propranolol and methysergide (75% improvement in methysergide vs. 71% improvement in 5-HTP) in reducing the frequency and severity of migraines41–45. Side effects can include nausea, diarrhea, and stomach pain, and it should be used cautiously with medications which increase serotonin levels (such as most antidepressants) due to potential risk of serotonin syndrome. Typical doses are around 100–200 mg, 2–3 times per day with meals.

 

  1. Fish oil (Eicosapentaenoic acid (EPA) + Docosahexaenoic acid (DHA))

Fish oils are found in the tissues of fish. They contain a certain type of fat called omega-3. Potential mechanisms for anti-inflammatory effects of fish oil include inhibition of inflammatory mediators (eicosanoids and cytokines), and synthesis of lipid suppressors of inflammation (resolvins)46. Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) give rise to these resolvins which are anti-inflammatory and inflammation resolving47. These compounds may relieve joint pain and stiffness in a similar way as non-steroidal anti-inflammatory drugs (NSAIDs)46,48. One study reported dramatic decreases in headache frequency (15 per month down to 2 per month) and decreases in headache severity (reduction from 5 to 3 on a 7-point scale)49. Fish oils have also been studied and found to be useful in other inflammatory conditions such as rheumatoid arthritis46,48,50–53. Large trials have showed a significant beneficial effect on pain, morning stiffness, number of painful and/or tender joints and NSAID consumption50. Recommended dosing consists of 30% EPA and DHA with a ratio of EPA to DHA of 1.5. Research suggests the minimum dose needed to reduce the joint inflammation associated with arthritis is 2.7 grams of omega-3 (EPA + DHA) daily, which could also be divided such as 900 mg EPA and 450 mg DHA twice daily.

 

  1. Melatonin:

Increasing evidence shows correlation between melatonin secretion and headache conditions. Melatonin supplementation has shown decreased headache intensity and duration. It is widely used as a sleep aid. Sleep is nature’s way of dealing with migraine. A dose of 3 mg is recommended to start for headaches including cluster headache. Higher doses up to 15 mg has been reviewed for use in cluster headache and have been used, if not making too groggy in the morning. The rationale behind using melatonin for cluster is that many theories regarding the cause of cluster headache center around the disruption of the normal circadian rhythm in the brain. This helps restore the normal circadian rhythm. It should be taken at least 2 hours before bedtime.

 

MITOCHONDRIAL SUPPLEMENTS

Mitochondria are the powerhouses within all cells of the body. These crucial metabolic organelles use oxygen to produce ATP, which is the primary energy source for the cell, and thus, for your body. Mitochondrial dysfunction leads to impaired oxygen metabolism and is suspected to play a role in migraine pathophysiology. Some migraineurs have been shown to have reduced mitochondrial activity which may lead to altered neuronal processing, and therefore a lower threshold for migraine attacks54–58. Riboflavin (vitamin B2), CoQ10 (ubiquinone; CoQ10), and alpha lipoic acid (thioctic acid) all play key roles in mitochondrial activity, and therefore have been implicated in migraine treatment by optimizing mitochondrial functioning.

 

  1. Riboflavin (Vitamin B2)

Riboflavin assists nerve cells in the production of ATP, a principal energy storing molecule. Riboflavin is an essential precursor to coenzymes involved in electron transport in oxidation reduction reactions within the Krebs cycle. This metabolic cycle is critical in production of ATP and generation of energy in the mitochondria, oxidative metabolism, maintaining membrane stability, and for all energy-related cellular functions59,60. It is necessary for many chemical reactions in the body. Brain riboflavin metabolism is suspected to affect migraine pathophysiology via several mechanisms, providing migraine preventive benefit.36,37

 

Riboflavin has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. The Canadian Headache Society Guidelines strongly recommend B2 for migraine prevention as well.15 There have been at least 3 clinical trials of riboflavin using 400 mg per day all of which suggested that migraine frequency can be decreased. All 3 trials showed significant improvement in over half of migraine sufferers. Trials of riboflavin have suggested significant improvements in migraine by up to 59%61. Riboflavin (Vitamin B2): 200 mg twice a day (or 400 mg daily). The supplement is found in bread, cereal, milk, meat, and poultry. Most Americans get more riboflavin than the recommended daily allowance, however riboflavin deficiency is not necessary for the supplements to help prevent headache. One side effect to be aware of is that it can turn your urine bright neon yellow, although this is not harmful. Recommended dosing is 200 mg twice daily (or 400 mg once daily).

 

  1. Coenzyme Q10 (Ubiquinone; Ubiquinol; CoQ10)

CoQ10 is present in every membrane of all cells in the body62. Similar to riboflavin, CoQ10 plays a crucial role in electron transport and energy metabolism given its heavy involvement in mitochondrial function. CoQ10 is incorporated into the mitochondria, where it facilitates the transformation of fats and sugars into energy, thus it is often marketed to be an “energy enhancer”. Studies have shown that a nutritional supplement of CoQ10 can reduce the frequency of migraine attacks by improving the energy production of cells as with riboflavin. It also functions as an antioxidant by protecting against toxic oxidative reactions in the body, and CoQ10 tissue levels are known to decrease with age19,63. In one study, CoQ10 was found to be low in about 1/3rd of patients studied, and when replaced, headache frequency improved64. Migraine frequency was shown to improve significantly in more than 61% of patients in one study65, and 50% of patients in another study,66 supporting use for migraine prevention.36 Other studies have also shown benefit in migraine prevention when combined with magnesium and feverfew as well.38 The Canadian Headache Society guidelines strongly recommend use of CoQ10.15 Suggested dosing is around 150 mg-200 mg twice a day.

 

  1. Alpha Lipoic Acid (Thioctic Acid)

Alpha lipoic acid enhances the metabolism of oxygen and energy production by mitochondria67, and has shown reduction of migraine frequency68 when studied. Doses are typically around 300 mg twice daily.

 

HERBAL PREPARATIONS

  1. Feverfew (Tanacetum parthenium)

Feverfew is a common garden herb native to Europe and popular in Great Britain as a treatment for disorders typically controlled by aspirin. The mechanism of action is unknown but is believed to be related to a chemical called parthenolide which helps the body use serotonin more effectively. Serotonin helps prevent migraine and assists with resolution when it occurs. Parthenolide also inhibits the release of histamine which is linked to pain and inflammation. Consistency of active ingredients in different products can be a problem. Some formulations don’t have the active ingredient (parthenolide) that prevents migraine. A parthenolide content of 0.2% is generally recommended.

 

Feverfew has a Level B (2nd highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society.14 This is a higher evidence recommendation than many of the prescription medications we use for migraine prevention. The anti-migraine action36–38,69–75 of Feverfew is felt to be related to the parthenolides within the leaves. Studies have shown that the parthenolides provide anti-inflammatory and analgesic effects through several mechanisms involved in the migraine process that normally lead to pain. These include inhibition of phospholipase A, prostaglandin biosynthesis and platelet aggregation, and actions on serotonin including release of serotonin from platelets and white blood cells, as well as interaction at various serotonin receptor subtypes19,76–89. Study results have been variable based on wide variations in the strength of the parthenolides and differences in the stability of feverfew preparations used. However, a new, more stable feverfew extract (MIG-99) was created and showed a significant improvement in patients with high-frequency migraine90,91. The recommended dosing is generally around 50 mg twice daily (standardized to a high parthenolide content of 0.7% and stability measures of parthenolide), or, preferably MIG-99 6.25 mg three times daily if it can be found.

 

  1. Butterbur Extract (Petasites hybridus)

Butterbur is an extract derived from the petisides hybridus root, which has been used for medicinal purposes since ancient times. Butterbur is a well-researched and proven herbal supplements for migraine prevention36,69,70,92. For many years, it was the only supplement with a Level A (highest) evidence recommendation for migraine prevention by the American Academy of Neurology and American Headache Society,14 with a higher evidence recommendation than many of the prescription medications we use for migraine prevention. However, this recommendation was withdrawn a few years ago given a small handful of cases of liver failure reported in Germany. Although it is classified as an herbal supplement in the US, it is a licensed pharmaceutical medicine in Germany (Petadolex). Its two active compounds, petasin and isopetasin, help reduce cerebral blood vessel spasm and stop the inflammatory cascade which occurs in migraine93–95. Butterbur is thought to act through anti-inflammatory inhibition of leukotriene biosynthesis for its analgesic effects but also has calcium channel regulatory properties, both of which play a role in migraine19.

 

Studies have also shown anti-inflammatory effects mediated through inhibiting the additional inflammatory enzymes cyclooxygenase and prostaglandin production96. Notably, this is also what gives aspirin its anti-inflammatory effect. Trials have shown very positive results with significant decreases in migraine frequency of up to 58-77%, with 91% reporting overall improvement97–100. Side effects can include burping/belching. Raw butterbur root contains toxic chemicals that must be filtered out during the manufacturing process. To be sure you are choosing a safe product, look for a formulation that does not contain pyrrolizidine alkaloids since these are toxic to the liver. Recommended dosing is typically around 75 mg twice daily (free of Pyrrolizidine Alkaloids (PAs), standardized to contain a minimum of 7.5 mg of petasin and isopetasin).

 

  1. Ginger (Zingiber Officinale)

Ginger has anti-histamine and anti-inflammatory properties such as blocking pain-producing prostaglandins101,102, and helps with circulation and potentially headache. It is also widely used to treat nausea and vomiting, which accompany migraine103, and this is what it is primarily useful for. Recommended dosing ranges from 100-200 mg three times per day to 150 mg twice daily (standardized to contain 20% of gingerol and shogaol (dosage).

 

  1. CBD (Cannabidiol)

There have been a multitude of studies documenting the analgesic and anti-inflammatory benefits of medicinal cannabis across many chronic pain syndromes104–106, and it has been a historical treatment for headache and migraine for centuries.105–109 The vast majority of supporting evidence of cannabis and cannabinoids involves various chronic pain syndromes. These benefits are hypothesized to extend to headache disorders such as migraine given overlapping neurobiological pathways of pain. Some data suggests that cannabinoids appear to work uniquely within the inherent anatomical pathways of migraine (including serotonergic triptan pathways) and pain.104,105,107–139 Unfortunately, the majority of data supporting the use of cannabis and cannabinoids in migraine and headache disorders is based on case series, case reports, surveys and anecdotal evidence.105,107,145–154,108,155–161,134,135,140–144 There has been one retrospective study of cannabis use in the treatment of migraine which reported strong statistically significant findings of benefit.162 There have been only two limited prospective trials of cannabinoids containing a control group in headache disorders. One reported significant benefit in chronic daily headache associated with medication overuse headache,163 and the other reported significant benefit in both the acute and preventive treatment of chronic migraine.164

 

Given the growing evidence of cannabis and cannabinoids in the treatment of chronic pain and other medical conditions, in February 2019 The World Health Organization (WHO) recommended that cannabis be rescheduled and removed from the most restrictive scheduling category. In January 2017, the National Academies of Sciences, Engineering, and Medicine concluded that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults.165 In 2014, the Canadian Pain Society revised their consensus statement to recommend cannabinoids as a third-level therapy for chronic neuropathic pain based on the abundance of supporting evidence and a NNT (number needed to treat) estimated at approximately 3.166

 

Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two predominant cannabinoids found in cannabis and are discussed in more detail here. CBD is several hundred more times anti-inflammatory than aspirin.104 There have been scientific, animal models, and limited human clinical trials documenting its anti-inflammatory and analgesic properties.167–176 In contrast to THC, CBD is non-intoxicating (no “high”).167 In November 2017, The World Health Organization (WHO) concluded that CBD exhibits no evidence for abuse or dependence potential, and that there is no evidence of public health related concerns associated with its use.177 In January 2018, the World Anti-Doping Agency (WADA) removed CBD from their prohibited list, no longer banning use by athletes.178

 

In December 2018, the Agriculture Improvement Act (Farm Bill) was signed into law in the United States. This legalized the agricultural growth and use of hemp (cannabis strains containing 0.3% THC or less) and hemp derivatives such as CBD, as well as removed hemp and its extracts (including CBD) from the Controlled Substances Act, making it no longer an illegal substance under federal law.

 

Thus, the use of CBD products has been exploding and is a new industry projected to exponentially increase into a multi-billion dollar industry179,180. Many patients are using these products for a variety of reasons181,182, most commonly in pain, including migraine prevention, given their easy access and availability. However, there are no studies evaluating CBD alone in treatment of migraine or any other headache disorders, so this is purely anecdotal. CBD products can readily be purchased online from a multitude of companies, in local health food and drug stores, and common retail pharmacies.183 CBD and suggested dosing (which are not currently clearly known) are discussed in much greater detail here.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

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IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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  162. Rhyne DN, Anderson SL, Gedde M, Borgelt LM. Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population. Pharmacotherapy. 2016;36(5):505-510. doi:10.1002/phar.1673 [doi]
  163. Pini LA, Guerzoni S, Cainazzo MM, et al. Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial. J Headache Pain. 2012;13(8):677-684. doi:10.1007/s10194-012-0490-1 [doi]
  164. Nicolodi M, Sandoval V, Terrine A. Therapeutic use of cannabinoids – Dose Finding, Effects, and Pilot Data of Effects in Chronic Migraine and Cluster Headache. Abstract presentation at 3rd Congress of the European Academy of Neurology (EAN), Amsterdam, 6/24/17. In: 3rd Congress of the European Academy of Neurology (EAN), Amsterdam 6/24/17. Amsterdam.
  165. Committee of the Health Effects of Marijuana: An Evidence Review and Research. The Health Effects of Cannabis and Cannabinoids. The Current State of Evidence and Recommendations For Research.Washington, DC: The National Academies Press.; 2017.
  166. Moulin D, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328-335.
  167. Russo EB. Cannabidiol Claims and Misconceptions. Trends Pharmacol Sci. 2017;38(3):198-201. doi:10.1016/j.tips.2016.12.004
  168. Pisanti S, Malfitano AM, Ciaglia E, et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175:133-150. doi:S0163-7258(17)30065-7 [pii]
  169. White CM. A Review of Human Studies Assessing Cannabidiol’s (CBD) Therapeutic Actions and Potential. J Clin Pharmacol. 2019;59(7):923-934. doi:10.1002/jcph.1387
  170. Palmieri B, Laurino C, Vadala M. Short-Term Efficacy of CBD-Enriched Hemp Oil in Girls with Dysautonomic Syndrome after Human Papillomavirus Vaccination. Isr Med Assoc J. 2017;19(2):79-84.
  171. Cunetti L, Manzo L, Peyraube R, Arnaiz J, Curi L, Orihuela S. Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay. Transplant Proc. 2018;50(2):461-464. doi:10.1016/j.transproceed.2017.12.042
  172. Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003;17(1):21-29.
  173. Philpott HT, O’Brien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017;158(12):2442-2451. doi:10.1097/j.pain.0000000000001052
  174. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936-948. doi:10.1002/ejp.818
  175. Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000;97(17):9561-9566. doi:10.1073/pnas.160105897 [doi]
  176. Costa B, Colleoni M, Conti S, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol. 2004;369(3):294-299. doi:10.1007/s00210-004-0871-3 [doi]
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  181. Velasquez-Manoff M. Can CBD Really Do All That? How one molecule from the cannabis plant came to be seen as a therapeutic cure-all. New York Times. https://www.nytimes.com/interactive/2019/05/14/magazine/cbd-cannabis-cure.html. Published May 14, 2019.
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  183. Schiller M. CVS and Walgreens Plan to Carry CBD Products: What’s Next for the Rapidly Growing Market? Cannabis Bus Times. April 2019. https://www.cannabisbusinesstimes.com/article/cvs-walgreens-carry-cbd-products-whats-next-for-market/.

 

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Last updated on December 3rd, 2020 at 02:52 am

UBRELVY vs. NURTEC ODT vs. REYVOW vs. TRIPTANS. NEW MIGRAINE ABORTIVE OPTIONS ARE FINALLY HERE, BUT WHAT ARE THE DIFFERENCES AND IS ONE BEST FOR YOU?

@Neuralgroover

BACKGROUND

Ubrelvy vs. Nurtec, Ubrelvy vs. triptans, Nurtec vs. triptans, Ubrelvy vs. Reyvow, Nurtec vs. Reyvow, Reyvow vs. triptans, Rimegepant vs. Ubrogepant, Ubrogepepant vs. triptans, Rimegepant vs. triptans, Lasmiditan vs. Ubrelvy, Nurtec vs. Lasmiditan, Lasmiditan vs. triptans, Ubrogepant vs. Lasmiditan, Rimegepant vs. Lasmiditan. How do you know which one to pick??? Let’s discuss how to pick the best one for you.

Since the development and availability of sumatriptan in 1992, the main migraine specific abortive available has been the triptans. Triptans work great for a lot of people. However, about 25% of patients do not respond to triptans. Others cannot tolerate side effects, or they cannot use them because of medical contraindications (such as coronary artery disease, peripheral artery disease, stroke, etc.). The triptans are discussed in more detail here. The alternatives to triptans have been the ergots (ergotamine, DHE) which can be complicated to use, tend to have an excess of side effects for many, and have the same medical contraindications as triptans. NSAIDs and over the counter analgesics are also commonly used, although many do not respond to or cannot take them due to other medical conditions. Even worse are opiates/opioids and butalbital medications such as fioricet, both of which have a high risk of leading to medication overuse headache (rebound headache), as discussed here.  For close to 3 decades, these have remained the only limited options of acute/abortive migraine treatment, despite migraine being such a widespread common disorder! Thankfully, these limited options have now expanded to 3 new migraine abortive options in adults between 2 new classes which became available commercially in 2020; the gepants and the ditans. These 3 new abortive medications are compared and contrasted with one another, as well as with the triptans in the table which I (exhaustingly) constructed below.

 

GEPANTS

The gepants were the first to emerge as new options, first with Ubrogepant (Ubrelvy) which became available from Allergan in January 2020 and then Rimegepant (Nurtec ODT (orally dissolvable tablet)) became available by Biohaven in February 2020. During a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP causes worsening inflammation around the brain (“sterile inflammation”), intensified pain signals, and dilation of the arteries surrounding the brain, which leads to increasing pain signals via the trigeminal nerve endings. Gepants work as CGRP receptor antagonists, which means they directly target and block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” these pathways of pain. So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans). By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

Many patients use once monthly CGRP antagonist monoclonal antibody (mAbs) self-injections (autoinjection devices) which are FDA approved for migraine prevention (Aimovig (Erenumab), Ajovy (Fremanezumab), Emgality (Galcanezumab), and Vyepti (Eptinezumab), which is a once quarterly 30 minute IV infusion). The CGRP mAbs are discussed in much greater detail and compared with one another here. These have little to no drug interactions and do not affect the liver or kidneys. However, patients often ask if these medications can be used with the gepants given similar mechanisms of action (although much different structure, molecule size, and metabolism). Further confirmatory research is needed, but it is theorized that these medicines can likely be used safely together, and they are metabolized by completely different mechanisms. The gepants are metabolized in the liver, while the CGRP mAbs are metabolized and cleared in the reticuloendothelial system. Furthermore, there is limited evidence suggesting that they may even provide a synergistic effect by working together, but more evidence is needed to confirm this. An insurance battle often ensues when trying to use the large molecule preventive CGRP mAbs with the small molecule abortive gepant medications (Nurtec, Ubrelvy), which also work by a CGRP mechanism. Insurance companies will often not allow these to be used together, despite no good scientific basis. Actually, there is some limited evidence showing that these medications can work synergistically together, which would make sense when taking their mechanisms of action into account. Specifically, there was a publication of data from only a 2-patient cohort showing that the use of these acute and preventive CGRP migraine therapies together can be successful and safe. These two patients had been using rimegepant (Nurtec) in a long-term safety study and had added erenumab (Aimovig). The combination of both successfully aborted 100% of their acute migraine attacks. Certainly we need need larger studies to confirm the suspicion that they likely work together synergistically.

 

The side effect profile of the gepants is minimal and similar to placebo compared to the triptans and their alternatives. This is really great to have new options with much less side effect potential. In addition, there is no interaction with using them and triptans, NSAIDs, or other acute meds in case they happen to be taken close together. These medications are not associated with addiction potential, or medication overuse headache (rebound), which is great! Compared to the triptans and ergots, these medications are NOT contraindicated in patients with stable cardiovascular or peripheral vascular disease or risk factors because they do not cause vasoconstriction (narrowing) of the arteries, which is a HUGE benefit. There are many patients who have been stuck in limbo unable to use standard therapies such as triptans due to other medical problems such as heart disease, so we finally have a safe alternative for them, which is another highlight of these medications. Safety of these medications in pregnancy or breastfeeding is unknown because they haven’t been studied, and therefore are not recommended. The primary drug interactions to be aware of with these medications are when used with other medications that are metabolized by the liver enzyme system called CYP3A4. Many commonly used medications are metabolized by this system. Strong or moderate inhibitors of CYP3A4 (which slow down the metabolism activity) will cause an increase in gepant exposure. Strong or moderate inducers of CYP3A4 (which increase the metabolism activity) will cause a decrease in gepant exposure and possibly decreased effectiveness. These medications should be avoided in patients with severe liver disease or end stage kidney disease such as those on dialysis.

 

Given that Ubrelvy and Nurtec ODT are of the same class, they each have their own marketing pitch to differentiate them, although the bottom line is that they are both excellent options.

 

Ubrelvy (Ubrogepant)

Allergan markets Ubrelvy as quickly relieving migraine pain within 2 hours with just one dose, and that complete elimination of migraine pain with one dose is possible. Furthermore, they highlight that they provide the option of being able to repeat a 2nd dose if needed (similar to how triptans are dosed), with a higher proportion of patients achieving pain freedom 2 hours after taking the optional second dose. They also claim effective relief whether Ubrelvy was taken right away at migraine onset or within 4 hours. The half life is 5-7 hours, so duration of effect is extended compared to many options that we had up to this point. The clinical data highlights of Ubrelvy are that at 1 hour Ubrelvy 50 mg becomes statistically superior to placebo for pain relief, and at 2 hours the 100 mg dose also becomes statistically superior to placebo for pain relief. At 2 hours, both the 50 mg and 100 mg doses become statistically superior to placebo for pain freedom as well as freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia). These benefits could extend into 24 and even 48 hours. In patients who received pain relief with the 1st dose and took an optional 2nd dose of 50 mg, 55% went on to become pain free 2 hours from that point.

Side effects were similar to placebo and the most common were nausea (placebo 2%, Ubrelvy 50 mg 2%, Ubrelvy 100 mg 4%), and somnolence (sleepiness) (placebo 1%, Ubrelvy 50 mg 2%, Ubrelvy 100 mg 3%).

They currently have a savings card program which should work with commercial insurances for $10 per month, which works out to $1 per pill (10 pills per month). You can get a digital copy of this savings card on your phone to show to the pharmacist if you text UBRELVY to 48764.

 

Nurtec ODT (Rimegepant)

Biohaven boasts that Nurtec ODT dissolves under or on the tongue in seconds, and starts working in minutes (15 minutes in some patients). They highlight that it does not require water or other liquids to take with the dose, so it can be taken anytime and anywhere. It is taken as a simple single strength single dose. They also point out that pain relief and pain freedom lasts up to 48 hours for many patients, which makes sense because it has the longest half-life (11 hours). The clinical data highlights of Nurtec ODT are that at 15 minutes, you get separation from placebo of both pain relief and return to normal function (but not yet statistically superior). At 1 hour, pain relief and return to normal function become statistically superior to placebo. At 1.5 hours, you get additional statistical superiority over placebo of pain freedom and freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia). For the vast majority of patients, the superiority of all of these trial endpoints over placebo remain sustained through 48 hours.

Side effects were similar to placebo and the most common was nausea (placebo 0.4%, Nurtec 2%).

They currently have a savings card program which should work with commercial insurances for $0 per month (8 pills per month). You can get a digital copy of this savings card on your phone to show to the pharmacist if you text NSAVE to 26789.

 

DITANS

Reyvow (Lasmiditan)

The ditans are another new class of migraine abortive, premiering with Lasmiditan (Reyvow) in January 2020 from Eli Lilly. Lasmiditan acts as a high affinity 5-HT1F (serotonin 1F) receptor agonist. The result of its action is a decrease in the release of inflammatory pain producing neurotransmitters and neuropeptides including CGRP from the trigeminal nerves during a migraine attack. These receptors are also involved in modulating other pain signals and blocking (inhibiting) other pain pathways. Notably, like the gepants, they also do not cause arterial vasoconstriction. Again, this is a tremendous benefit and another great option in patients who may not be able to use triptans due to medical contraindications such as coronary or peripheral vascular disease. Caution should be used with other serotonergic drugs given a potential for serotonin syndrome, which was reported in clinical trials.

Similar to the gepants, the Reyvow clinical data highlights showed superiority over placebo at trial endpoints of 2 hour pain freedom, freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia), and pain relief.

 

In a driving study, 50 mg, 100 mg, or 200 mg doses of Lasmiditan significantly impaired subjects’ ability to drive, and more sleepiness was reported at 8 hours following a single dose compared to placebo. Therefore, patients should wait at least 8 hours between dosing and driving or operating machinery. This can certainly be a drawback in terms of being a treatment option for many patients as the goal of abortive therapy is partly to be able to maintain and restore function in order to not disrupt work, plans, etc. However, if you are in a position where this would not be an issue for you, it could certainly be a valid option to have in your migraine war chest. It should also be used with caution in combination with alcohol or other central nervous system depressants.

 

Notably, Lasmiditan is a Schedule V controlled substance compared to the other abortive options. Schedule V represents the lowest abuse potential category from the DEA. The reason is because in a human abuse potential study, doses of 100 mg, 200 mg, and a supratherapeutic dose of 400 mg were associated with statistically significantly higher “drug liking” scores than placebo, indicating possible abuse potential. However, it had statistically significantly lower “drug liking” scores compared to alprazolam 2 mg. Lasmiditan also produced adverse events of euphoria and hallucinations to a greater extent than placebo, although it was a low frequency (about 1% of patients). They currently have a savings card program which should work with commercial insurances for $0 per month (4 pills per month).

 

SUMMARY

The chart below compares and contrasts the treatment outcomes data between Rimegepant, Ubrogepant, Lasmiditan, and Sumatriptan (as representative of the triptan class since it was the first developed). The source of the data comes from the key trials of each medication, as well as some data obtained directly from the pharmaceutical companies. It’s important to note that the trials for each medication did not all include the same data point evaluations, so not all of the comparison data is available across the medications to compare. Also, this data is not reflective of head to head trials between these medications. The data is derived from separate independent trials, many times of which there were variations in study design and endpoints. So, they should not be thought of as head to head comparisons necessarily. In addition, the original triptan studies did not include many of the treatment outcome data points that have become more commonly used since they were developed such as 8 hour data, 2-48 hour data, most bothersome symptom, etc. Therefore, many of these data points within the columns of the different medications may be labeled by N/A (not available).

 

Overall, these are all very effective and useful medications to keep in mind for your migraine abortive war chest. They are all a welcome and much needed option for the abortive (acute) treatment of migraine. Notably, Ubrelvy, Nurtec ODT, and Reyvow were all proven to be statistically superior to placebo at 2 hours post-dose (some sooner) in terms of pain freedom, pain relief, and freedom from most bothersome migraine symptom (nausea, sensitivity to light (photophobia) or sensitivity to sound (phonophobia)). So there is no “bad” option. Many of the data points are fairly similar with some slight variations, and some data points weren’t compared. Regardless, I have highlighted some of the key differences to take note of in bold print. I hope this data can provide some guidance on some of the differences in these medications which may help to better select them based on the treatment goals, setting of use, and other patient characteristics.

 

Rimegepant Ubrogepant Lasmiditan Sumatriptan (100 mg)
Class Gepant Gepant Ditan Triptan
Mechanism of Action CGRP receptor antagonist CGRP receptor antagonist 5HT1F agonist 5HT1B and 5HT1Dagonist
Available dosing 75 mg orally dissolvable tablet 50 mg, 100 mg pill 50 mg, 100 mg, 200 mg (100 mg x 2) pill 25 mg, 50 mg, 100 mg pill; 3 mg, 4 mg, 6 mg injection; 5 mg, 10 mg, 20 mg nasal spray
Max dose per 24 hours 75 mg 200 mg 200 mg 200 mg
Pills per prescription (standard, may be more depending on insurance) 8 10 8 9
Dosing frequency 1 dose/24 hours Dose can repeated once in 2 hours; 2 doses/24 hours 1 dose/24 hours Dose can repeated once in 2 hours; 2 doses/24 hours
Suggested number of migraine attacks treated per 30 days 15 (however, currently also being studied as a daily preventive) 8 4 10
Time to reach statistically significant pain relief 60 minutes (however, there was a 15 minute measured clinical beneficial effect) 60 minutes with 50 mg or higher doses 30 minutes with 100 mg or higher doses;

60 minutes with 50 mg dose

30 minutes with 50 mg or higher doses
1 hour significant pain relief 37%

31% (placebo)

43% (50 mg)

N/A (100 mg)

36.7% (placebo)

37.3% (50 mg)

»41% (100 mg)

»46% (200 mg)

30.6% (placebo)

20-35% (100 mg)

12-21% (placebo)

Differences in pain relief at 15 minutes 8%

5% (placebo)

N/A N/A N/A
Differences in pain relief at 30 minutes 19%

17% (placebo)

19% (50 mg)

N/A (100 mg)

20% (placebo)

»15% (50 mg)

17.5% (100 mg)

19.1% (200 mg)

13.4% (placebo)

11% (100 mg)

12% (placebo)

2 hour pain relief 59%

43% (placebo)

61.7% (50 mg)

61.4% (100 mg)

48.7% (placebo)

59% (50 mg)

59.4-64.8% (100 mg)

59.5-65% (200 mg)

42.2-47.7% (placebo)

46-67% (100 mg)

18-44% (placebo)

2 hour pain freedom 21%

11% (placebo)

20.5% (50 mg)

21.2% (100 mg)

13% (placebo)

28% (50 mg)

28-31% (100 mg)

32-39% (200 mg)

15-21% (placebo)

22-33% (100 mg)

3-13% (placebo)

8 hour pain freedom with 1 dose 56%

33% (placebo)

82.3% (50 mg)

82.7% (100 mg)

69.8% (placebo)

N/A N/A
8 hour pain relief with 1 dose 74%

56% (placebo)

92% (50 mg)

N/A (100 mg)

82% (placebo)

N/A N/A
% of patients with 1st dose pain relief who achieved pain freedom after 2nddose N/A 54.7% (50 mg/50 mg)

33.3% (50 mg/placebo)

51.6% (100 mg/100 mg)

33.3% (100 mg/placebo)

N/A N/A
Sustained pain freedom 2-24 hours 15.7%

5.6% (placebo)

13.6% (50 mg)

15.4% (100 mg)

8.4% (placebo)

17.2% (50 mg)

14.8-17.9% (100 mg)

18.6-22.7% (200 mg)

7.6-13.4% (placebo)

N/A
Sustained pain relief 2-48 hours 47.8%

27.7% (placebo)

31.5% (50 mg)

34% (100 mg)

17.5% (placebo)

N/A N/A
2 hour absence of most bothersome migraine symptom 35%

27% (placebo)

38.7% (50 mg)

37.7% (100 mg)

27.6% (placebo)

41% (50 mg)

41-44% (100 mg)

41-49% (200 mg)

30-33% (placebo)

N/A
8 hour absence of most bothersome migraine symptom N/A 90.9% (50 mg)

92.4% (100 mg)

77.7% (placebo)

N/A N/A
Time to peak plasma concentration TMAX 1.5 hours 1.5 hours 1.8 hours 1.5-2.5 hours
½ life 11 hours 5-7 hours 5.7 hours 2-2.5 hours
Time to reach pharmacologically active concentration 15 minutes Within 11 minutes N/A N/A
Time the pharmacologically active concentration is maintained 48 hours 12 hours N/A N/A
Notable side effects Nausea

2%

0.4% (placebo)

Nausea

2% (50 mg)

4% (100 mg)

2% (placebo)

 

Somnolence/Sedation

2% (50 mg)

3% (100 mg)

1% (placebo)

Nausea

3% (50 mg)

4% (100 mg)

4% (200 mg)

2% (placebo)

 

Somnolence/Sedation

6% (50 mg)

6% (100 mg)

7% (200 mg)

2% (placebo)

 

Dizziness

9% (50 mg)

15% (100 mg)

17% (200 mg)

3% (placebo)

 

Paresthesias

3% (50 mg)

7% (100 mg)

9% (200 mg)

2% (placebo)

Widely variable, most common: Dizziness, fatigue, paresthesias, sedation, nausea, palpitations, anxiety, muscle tightness sensation in chest/neck/throat

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

 

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Last updated on November 24th, 2020 at 04:48 pm

CBD (CANNABIDIOL) FOR MIGRAINE, HEADACHE, AND PAIN. EVERYTHING YOU NEED TO KNOW.

@Neuralgroover

BACKGROUND

CBD (cannabidiol) for migraine, headache, pain, chronic pain, arthritis, and other medical conditions are topics that patients are increasingly asking about. Why? CBD is everywhere! You can buy it at the local grocery store, supplement store, gas station, video rental store, and almost anywhere else nowadays. There are hundreds of brands. Is it right for you? Will it work? How do you take it? How do you know which products are of good quality and are safe? Are there downsides? Are there side effects? Will you test positive on a drug screen? These are a few of the many questions you likely have. Our patients ask about CBD use all the time in regard to migraine and pain. So, I decided to write this blog to provide an overview and answer these burning questions you may have!

 

There have been a multitude of studies documenting the analgesic and anti-inflammatory benefits of medicinal cannabis across many chronic pain syndromes1–4, and it has been a historical treatment for headache and migraine for centuries.2,3,5–7 An extensive discussion of medicinal cannabis, or medicinal marijuana, for chronic pain, headache, and migraine can be read here. The vast majority of supporting evidence of cannabis and cannabinoids involves various chronic pain syndromes. These benefits are hypothesized to extend to headache disorders such as migraine given overlapping neurobiological pathways of pain. Some data suggests that cannabinoids appear to work uniquely within the inherent anatomical pathways of migraine (including serotonergic triptan pathways) and pain.1,2,5–37 Unfortunately, the majority of data supporting the use of cannabis and cannabinoids in migraine and headache disorders is based on case series, case reports, surveys and anecdotal evidence.5,6,32,33,38–57 There has been one retrospective study of cannabis use in the treatment of migraine which reported strong statistically significant findings of benefit.58 There have been only two limited prospective trials of cannabinoids containing a control group in headache disorders. One reported significant benefit in chronic daily headache associated with medication overuse headache,59 and the other reported significant benefit in both the acute and preventive treatment of chronic migraine.60

 

The endocannabinoid system is a normal and important biological system within everyone. It plays a role in many regulatory physiological processes across all organ systems, and is widely distributed throughout the central nervous system (brain and spinal cord) and peripheral nervous system (nerves outside of the spinal canal). Notably, it plays a strong role in pain pathways. This system works by the interaction of our own natural endocannabinoids turning on or turning off various endocannabinoid receptors throughout our body.

 

Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are the two predominant cannabinoids found in cannabis (marijuana). Cannabinoids are unique to the cannabis plant, and can be thought of as the “plant equivalents” of our own endocannabinoids. So, they interact with the same endocannabinoid receptors in our body as our own endocannabinoids do. Given the growing evidence of cannabis and cannabinoids in the treatment of chronic pain and other medical conditions, in February 2019 The World Health Organization (WHO) recommended that cannabis be rescheduled and removed from the most restrictive scheduling category. In January 2017, the National Academies of Sciences, Engineering, and Medicine concluded that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults. In 2014, the Canadian Pain Society revised their consensus statement to recommend cannabinoids as a third-level therapy for chronic neuropathic pain based on the abundance of supporting evidence and a NNT (number needed to treat) estimated at approximately 3 (the number of patients needed to treat for 1 of them to receive benefit). So naturally, there has been a quickly growing public interest in these potential therapies for a variety of reasons, especially in pain disorders.

 

THC causes the psychoactive qualities (“high”) of cannabis. THC has been shown to be 20 times more anti-inflammatory than aspirin and 2 times as anti-inflammatory as hydrocortisone. It is also a potent anti-emetic (anti-nausea), which is why there are two FDA-approved synthetic THC medications for chemotherapy related nausea and vomiting (Dronabinol, Nabilone). The existing literature and research on the treatment of pain have primarily studied cannabis itself with its variable and often undefined combinations of THC, CBD, other cannabinoids, terpenes, and other constituents. The medicinal benefits of cannabis are suspected to be from the “entourage effects” from synergistic action (working together) between various cannabinoids such as THC and CBD, and terpenes.1,61

 

In contrast to THC, CBD is non-intoxicating (no “high”). CBD has been shown to be several hundred more times anti-inflammatory than aspirin. Greater than 65 molecular receptor targets and greater than 80 mechanisms of action have been identified. There have been scientific, animal models, and very limited human clinical trials documenting its anti-inflammatory and analgesic (pain-relieving) properties. However, there are no high-quality research studies to date evaluating isolated pure CBD in any pain, migraine, or other headache disorders. So, it is unclear how much benefit CBD in isolation provides outside of the presumed entourage effects that it contributes to.

 

In November 2017, The World Health Organization (WHO) concluded that CBD exhibits no evidence for abuse or dependence potential, and that there is no evidence of public health related problems associated with its use. In January 2018, the World Anti-Doping Agency (WADA) removed CBD from their prohibited list, no longer banning use by athletes. In December 2018, the Agriculture Improvement Act (Farm Bill) was signed into law. This legalized the agricultural growth and use of hemp (cannabis strains containing 0.3% THC or less) and hemp derivatives such as CBD. The Farm Bill also removed hemp from the Controlled Substances Act, making it no longer an illegal substance under federal law. To review, up until the Farm Bill was passed, any form of cannabis or cannabis derivatives (including CBD) have been federally illegal since the Controlled Substance Act of 1970, which is when cannabis was changed to a Schedule 1 drug of which it has remained since. Therefore, it is important to remember that cannabis chemovars (strains) and CBD oils with greater than 0.3% THC are still considered marijuana, and thus are illegal federally, require a medical marijuana card for use, and are illegal to cross state lines with. In May 2019, TSA began to allow travel with CBD products containing 0.3% or less of THC.

 

Thus, the use of CBD products has been exponentially increasing for a wide variety of uses, including pain and headache, and anecdotal benefits are commonly reported. Although the various CBD companies provide guidance on dosing, there are no standardized dosing guidelines on optimal dosing, and strengths and frequencies used are widely variable. Some cannabinoid experts feel that most over the counter bought CBD products have too low of milligram content to have true physiological effects based on the high dose needed to enter the central nervous system through the blood-brain barrier. On the other hand, some suggest that “micro-dosing” with the lower CBD doses found in many products is enough to help replace endocannabinoid deficiencies. These dosing uncertainties have yet to be clarified and confirmed scientifically. Pure isolated CBD has never been evaluated prospectively in a randomized controlled trial in the treatment of migraine, headache, or pain to date. So, its use in the treatment of pain disorders including migraine remains primarily anecdotal at this time, but we anticipate future trials will provide more objective scientific data. The FDA is currently gathering and assessing available objective scientific data in anticipation of providing general dosing guidelines and recommendations of use.

 

SAFETY AND SIDE EFFECTS

CBD is generally very well tolerated, and pure CBD is not felt to be sedating. Actually, low to moderate doses are often more alerting.62 Early anecdotal literature involved CBD with sedating components (full spectrum products) including trace THC, other cannabinoids, and terpenes. For example, myrcene is a terpene often attributed to the “couch lock” phenomenon of some cannabis chemovars (strains). So, the sedation was not from the CBD, but actually from these other associated components. More recent studies (up to 600 mg pure CBD) have reported no sedative side effects.

 

There is one FDA approved form of CBD called Epidiolex, and these trials are what most of the known CBD safety data comes from. This is a purified cannabis derived form of CBD which was FDA approved in June of 2018 for some forms of refractory pediatric epilepsies.63 Dosing ranges from 5 to 20 milligrams per kilogram body weight total daily dose, which is divided between a morning and evening dose. These does are significantly higher than any form of over the counter non-prescription forms of CBD commonly sold. CBD is metabolized (broken down) in the liver. So, patients with liver disease many need to be more cautious with their dosing. In the Epidiolex studies, there was a slight elevation in liver enzymes in some patients. However, the vast majority of these liver enzyme elevations were in patients using the highest 20 milligram per kilogram daily dose and particularly when CBD was also being used with other anti-seizure medications, especially valproate and clobazam. This risk was much lower in patients outside of these categories. None the less, caution should be used when CBD is used with other medications that are metabolized by the same liver enzyme systems to avoid causing high or low levels of other medications. For example, high doses of CBD (such as those in the Epidiolex trials) may increase levels of certain medications such as warfarin, macrolide antibiotics, calcium channel blocker blood pressure medications, benzodiazepines, cyclosporine immunosuppressants, sildenafil, antihistamines, antidepressants, antipsychotics, antiretrovirals (such as HIV meds), and some antiseizure medications (such as clobazam), to name a few. With that said, the more commonly used doses bought over the counter are nowhere near the high doses of CBD in Epidiolex, so the clinical relevance of CBD use with these liver interactions is unclear at much lower doses. For example, Sativex studies (a whole plant CBD rich sublingual spray) found no interactions with liver enzyme systems with 40 mg CBD. The bottom line is that there are still many uncertainties so it is better to use caution until future studies can help clarify these questions.

 

In the Epidiolex studies, the most common adverse effects in a minority of patients were somnolence, lethargy, drowsiness, fatigue, diarrhea, decreased appetite, and nausea/vomiting. However, these side effects were in patients who were also using other anti-seizure medications (virtually all of which have drowsiness as a universal side effect). In addition, Epidiolex is about 98% pure CBD, but still contains 0.15% or less of THC, traces other cannabinoids and terpenes at a dose of 10 milligrams per kilogram per day. Therefore, these side effects are most likely to be related to these other factors rather than from the CBD content itself.

 

DIFFERENCES IN CBD PRODUCT TYPE, QUALITY, AND SAFETY

CBD has a wide variety of formulations from oral (primarily oils), tinctures, vaporization, and topical creams. Full spectrum or “whole plant” oral CBD products are the most popular. They are most likely to provide the “entourage effects” of cannabis. They contain everything the cannabis plant contains including CBD, trace THC (should be ≤0.3% per Federal law), terpenes, and flavonoids. Broad spectrum CBD products can be thought of as full spectrum without the trace THC. CBD isolate products consist of CBD isolated from all plant contents, without trace THC. It is important to know that use of these products may have a risk of testing positive on a marijuana drug test (which tests for THC). Although this risk is very low and can also be influenced by differing metabolisms between people, it is still a risk to be aware of. The risk of this correlates with the presence of trace THC and this risk would be highest in full spectrum, followed by broad spectrum, followed by CBD isolate products. Lastly, there is a misconception that CBD converts into THC in the human body. This is not true, and there is no evidence of this happening in the human body, and actually more evidence that it does not happen.62 This notion was based on an old lab-based experiment which involved acids and conditions which are not reflective of normal human physiology.

 

CBD products chosen should include independent 3rd party laboratory testing for content and quality. The reason is because there are so many CBD companies and products, and many of them are of low quality. In 2017, there was a study published in the Journal of the American Medical Association (JAMA) which evaluated 84 CBD products analyzed from 31 different companies, including 40 oils, 24 vaporization liquids, and 20 tinctures.64 Only about 30% of the products were labeled accurately with what they claimed to contain, while about 70% of the products were inaccurately labeled based on actual CBD content (43% had higher than advertised CBD, 26% had lower than advertised CBD). In addition, 21.4% had high levels of THC, above legal limits.

 

Another study looked at 13 CBD products tested across Los Angeles and New Jersey.65 Five of them (almost half) had no traceable CBD, and only 1 had an accurately advertised amount of CBD! Two had high THC (3 mg), 1 CBD gel cap product was contaminated with a deadly strain of E. Coli (shiga toxin), and 2 had potentially dangerous levels of ethanol.

 

In 2017, 5 patients in Utah developed seizures, confusion, coma, and hallucinations with a labeled “CBD” product, and 52 patients were harmed through 2018 with this product. This “CBD” product actually contained a synthetic cannabinoid and no CBD at all. The International Cannabis and Cannabinoid Institute in the Czech Republic assessed 29 CBD products and found that 69% exceeded the recommended levels of polycyclic aromatic hydrocarbons. These are known carcinogens and genotoxic mutagens according to International Agency for Research on Cancer. Unregulated CBD products may contain pesticides or heavy metal contamination as well.

 

CONCLUSIONS

In summary, CBD shows analgesic and anti-inflammatory effects in scientific and animal models, but there is limited data involving human studies. However, this should be changing soon now that CBD is federally legal with easier access to research. None the less, there may be a wide variety of tremendous therapeutic potential to be harnessed. Non-FDA approved forms of CBD may have inconsistent levels of CBD, THC, and contamination. Therefore, non-FDA approved forms of CBD should be from companies using independent 3rd-party lab analysis to confirm quality and contents until FDA regulations are available. It is important to know that CBD involves drug interactions with some common liver enzyme metabolism systems, but dosing threshold to interfere with other medications being metabolized in these same pathways is unclear and needs to be further clarified.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on November 24th, 2020 at 04:49 pm

REBOUND HEADACHE (MEDICATION OVERUSE HEADACHE); WHAT IT IS, AND HOW TO BREAK FREE FROM THE VICIOUS CYCLE.

@Neuralgroover

 

 

Chronic daily headache being endlessly fueled and driven by rebound headache (medication overuse headache or MOH) is one of the most common headache disorders that headache specialists encounter every day in clinic. Chronic daily headache refers to 15-30 days of headache per month on average for 3 or more months. The most common cause of chronic daily headache is typically chronic migraine, in which at least 8 days out of those 15-30 days per month have migrainous characteristics (throbbiness, throbby, pounding, pulsating pain with nausea and/or sensitivity to light (photophobia) and sound (phonophobia)).

 

Patients that have a prior or current history of headaches such as migraine or tension-type headaches tend to be highly susceptible to developing rebound headache/MOH when certain medications are being used too frequently, but it predominantly occurs in patients with a history of migraine. The overused medications may be actively used for headache (usually the case), but they may also be used for something entirely different such as back pain, nerve pain, arthritis pain, or anything else. The reason these medications are being used doesn’t matter as much as the frequency that they are being used. When certain medications are used too frequently, it will inadvertently cause the patient’s prior migraines to emerge and begin to increase in frequency and severity until it eventually evolves over time into a chronic daily headache with worsening severity. Once someone is stuck in the rut of chronic daily headache from chronic migraine and rebound headache/MOH, it can be very challenging to pull them back out of this cycle, and the rebound/MOH must be eliminated before improvement can occur. In addition, preventative medications (daily medicines used to lessen the frequency and/or severity of headaches) and abortive (“as-needed” at headache onset) pain medications generally become less effective in the setting of rebound/MOH.

 

Research has shown that medication overuse can transform episodic migraine (0-15 days of headache per month) to chronic migraine (15-30 days of headache per month) if the following medications are used at the following frequencies:

Greater than 10 days per month for 2 or more consecutive months of over the counter (OTC) pain medications (Tylenol, Excedrin, Acetaminophen, Aleve, Naproxen, Motrin, Advil, Ibuprofen, or other non-steroidal anti-inflammatories (NSAIDs)).

Greater than 10 days per month for 2 or more consecutive months of triptans (Sumatriptan, Rizatriptan, Zolmitriptan, Almotriptan, Frovatriptan, Naratriptan, Eletriptan).

Greater than 8 days per month for 2 or more months of any narcotic, opioid, or opiate medication (Vicodin, Norco, Hydrocodone, Oxycodone, Oxycontin, Percocet, Tramadol, Ultram, Ultracet, Morphine, Codeine, Dilaudid, etc.).

Greater than 5 days per month for 2 or more months of any butalbital containing medication (Fioricet, Fiorinal, Esgic); (also known as “the headache specialist’s worst enemy”).

 

The chronic daily headaches will never improve until a weaning detoxification from the overused medications happens. It can take up to 6-12 weeks for improvement to start to occur beginning after there is a consistent detoxification and minimizing use of the offending medication. This time-frame may vary depending on the medicine used, duration of use, frequency of use, and quantity of use. It is also important to know that as the patient is weaning and detoxing from the overused medications, headaches will commonly get worse (rebound) before they get better. The hardest part of breaking out of this cycle can be getting through that rebound hump. Unfortunately, there is not typically a “quick fix” for this scenario.

 

This process of weaning and detoxification is generally accompanied by starting and adjusting preventative daily headache medications by the patient’s physician. A general slow wean off of overused medications is seen below, and can be adjusted based on quantity and frequency of the overused medication:

Week 1: If using daily, decrease to half of the amount of medication typically used daily (for example, if taking Tylenol 4 times per day, decrease to 2 times per day, etc.).
Week 2: Use no more than 6 days per week.
Week 3: Use no more than 5 days per week.
Week 4: Use no more than 4 days per week.
Week 5: Use no more than 3 days per week.
Week 6: Use no more than 2 days per week or less.

 

Some people prefer to get through this weaning process faster rather than a slow wean such as this. Some choose to stop their overused medications “cold turkey” to expedite the process. This should be discussed with your physician because it can be medically unsafe to abruptly stop some medications such as fioricet, fiorinal, butalbital, opioids and opiates which can result in seizures, irregular heart rhythms, blood pressure changes, or other withdrawal syndromes. A “bridging” medication to help “bridge” out of this cycle is often used, or provided as a rescue to save for use during a slow wean to take if the rebound headache becomes intolerable. These bridging rescue medications may include a course of steroids, NSAIDs, IV infusions, or many other options depending on what medicine is being weaned and other medical conditions present. The bottom line is that it can be a painful, frustrating, and challenging process to pull out of a rebound/MOH cycle. So hang in there and stick with it because once you successfully get out of this rut, you’ll be happy you did!

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on November 24th, 2020 at 04:50 pm

WHAT ARE THE TRIPTANS AND WHICH IS BEST FOR YOU? HOW TO FINE-TUNE WHICH TRIPTAN WILL BE MOST EFFECTIVE SINCE NOT ALL TRIPTANS ARE CREATED EQUAL.

@Neuralgroover

 

Imitrex vs. Maxalt, Zomig vs. Maxalt, Amerge vs. Relpax, Frova vs. Imitrex, Maxalt vs. Relpax, Zomig vs. Imitrex, Frova vs. Amerge, Imitrex vs. Treximet. Maxalt vs. Frova. Axert vs. Imitrex. What are the best triptans to use? Well let’s back up a little first. The ergot based medications such as DHE (dihydroergotamine) and cafergot (ergotamine + caffeine) have been the oldest migraine abortive medications used, which are still used today. However, they often have many side effects for patients and eventually the migraine specific triptans were developed for aborting migraine. Since 1991 (when Sumatriptan was first approved), the triptans have been the first and only migraine specific abortive medications available up until 2020 when two new classes of migraine specific abortive medications (gepants, ditans) have become available. These new migraine abortive medications can be read about in more detail here.

 

The first triptan developed was sumatriptan in 1991 and since that time there have been a total of 8 triptan options to choose from. They work by activating (agonist) the serotonin sub-receptor 5-HT1B. The result of activating this receptor is that it helps to constrict (narrow) the dilated inflamed pain-producing meningeal blood vessels which occurs during a migraine attack. The 5-HT1B receptors are also present in the brainstem, and likely play a role in modulating the electrical event of a migraine. Triptans also work by activating (agonist) the serotonin sub-receptor 5-HT1D. The result of activating this receptor is that they stop the trigeminal nerves from releasing a variety of inflammatory proteins around the brain and blood vessels which normally leads to pain during a migraine attack. This also interferes with normal pain processing between the brainstem and the brain (helps to block this electrical transmission), and it helps to block the nausea and vomiting centers in the brainstem, which limits those symptoms.

 

Triptans are all similar in mechanism of action. However, there are many differences which allow them to be tailored and fine-tuned towards different types of migraine characteristics, as discussed below. This is a very important clinical point that is almost always overlooked by most physicians prescribing these medications if they are not headache specialists. Tailoring triptans to specific migraine characteristics can make a dramatic difference in its effectiveness since triptans are not all one in the same medication. The information below can be discussed with your doctor to hopefully get a better response to your triptan therapy.

 

TRIPTAN OPTIONS:
-Sumatriptan: oral, subcutaneous injection, needle-less subcutaneous injection, nasal spray, breath-powered intranasal delivery system
-Zolmitriptan: oral, orally dissolvable tablet, nasal spray
-Rizatriptan: oral, orally dissolvable tablet
-Almotriptan: oral
-Eletriptan: oral
-Sumatriptan/Naproxen: oral
-Frovatriptan: oral
-Naratriptan: oral

 

GROUP 1 TRIPTANS:
-Faster onset of action, higher potency (thus can have higher side effect potential), tend to have a higher 24-hour migraine recurrence
-Sumatriptan, Sumatriptan/Naproxen, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan

 

GROUP 2 TRIPTANS:
-Slower onset of action, lower potency (thus often have lower side effect potential), lower 24-hour migraine recurrence since the duration of action is longer:
-Frovatriptan, Naratriptan

 

FINE-TUNING YOUR TRIPTAN CHOICE: Remember the mnemonic CORN, and this will help to narrow down the best triptan to consider:

Contraindications
Onset to peak pain
Recurrence of migraine after treatment
Nausea and vomiting severity

Contraindications: This is not an exhaustive list, but are the most common. Your doctor should be well aware of when triptans should not be used.
-Known vascular disease (coronary artery disease, peripheral vascular disease, history of stroke)
-Vascular risk factors (poorly controlled hypertension, hyperlipidemia, diabetes, smoking, premature family history of coronary artery disease (men less than age 55, women less than age 65), postmenopausal women, etc.
-Kidney or liver failure
-Prinz-Metal angina

 

Onset to migraine peak pain:
-Group 1 triptan (quicker onset) is generally much more useful than a Group 2 triptan (slower onset).
-A subcutaneous injection or nasal spray triptan will typically be most helpful if:
-Patient wakes with migraine already ongoing (waking migraine)
-Migraine hits its peak pain level within 30 minutes or so

 

Return of migraine after treatment:
-If migraine recurrence occurs within 24 hours (for example it goes away with the triptan, but keeps returning later in the day or the next day), or the migraine is usually multiple consecutive days long (such as menstrual migraine):
-Combine the 1st dose of the triptan with an NSAID (such as Naproxen)
-Use a group 2 triptan (Naratriptan vs. Frovatriptan)

 

Nausea and vomiting severity:
-If nausea and vomiting occur early in the attack, or are severe to where it is hard to keep a pill down without vomiting it back up:
-A subcutaneous injection or nasal spray triptan should be used.
-Of note, dissolvable triptan tablets are still absorbed by the gastrointestinal tract, not sublingually. So, vomiting will still make this route ineffective, similar to a regular pill.

 

TRIPTAN PEARLS IN FURTHER FINE-TUNING TRIPTAN CHOICES:

Sumatriptan:
-Highest potency (in subcutaneous form) and quickest onset (subcutaneous > nasal spray) of triptans
-Greatest flexibility is dosing route options

Rizatriptan:
-Fastest onset of oral triptans
-Greatest likelihood of 2h pain-free and sustained pain-free response
-Propranolol increases its serum concentration, so 5mg per dose should be if used together

Zolmitriptan:
-Most likely to treat persistent headache when 1st dose fails

Almotriptan:
-The group 1 triptan with the least side effects

Eletriptan:
-Highest potential for drug interactions. Decrease dosage with CYP3A4 drugs such as macrolides, fungal, HIV, etc.

Naratriptan:
-The “gentle triptan” with the least side effects given its slower onset of action
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)
-Does not have monoamine oxidase metabolism, so it can be given with MAOI (as can Eletriptan and Frovatriptan)

Frovatriptan:
-Low side effect potential given its slower onset of action
-Longest half life
-Low 24 hour migraine recurrence rate
-Good choice to give shortly prior to an expected and known migraine trigger (menstruation, air travel, etc.)

 

CONCLUSIONS:
The triptans were and have been a game changer for millions of migraine patients in aborting migraine attacks. Using the highest available triptan dose is also generally recommended to see the full effect. We see many patients who have “failed triptans”, but on further history they were put on very low doses (such as 25 mg sumatriptan, when 100 mg is the standard dose). Even so, about 25% of migraineurs do not respond to triptans, only 1/3rd are pain-free at 2 hours, and only 17-25% remain pain-free at 24 hours. Therefore, although the majority respond well to triptans, not everyone does. Luckily, there are other medication options including two brand new classes of migraine abortive medications (gepants, ditans), and these are  detailed here.

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Last updated on November 25th, 2020 at 01:20 pm

CHIARI MALFORMATION HEADACHE, AND WHY YOU MAY STILL HAVE A DAILY HEADACHE FOLLOWING CHIARI DECOMPRESSION SURGERY.

@Neuralgroover

 

 

Chiari malformation is a common anatomical variation, specifically type I which this blog summarizes. It is most often a benign and asymptomatic finding found incidentally during routine imaging of the brain when an MRI or CT is done for other reasons, especially headache. The difficulty is often trying to associate the likelihood of a patient’s symptoms with the Chiari malformation vs. other headache disorder such as migraine, chronic migraine, and occipital neuralgia which can all have overlapping characteristics. Internet searching will give you a very long list of reported symptoms caused by Chiari malformation, many of which are inaccurate. Chiari malformation that is truly related to a patient’s symptoms typically include a “pegged” appearance of the cerebellar tonsils (back and bottom part of the cerebellum) which are pointed rather than rounded, suggesting compression at the cervicomedullary junction (area where the brainstem and upper cervical spinal cord merge between the bottom of the skull and upper cervical spine). The illustration above highlights this appearance compared to a normal brain. When this appearance is present, the patient often does have symptoms that correlate to the Chiari. Unfortunately, most of the time the Chiari malformation is not as extensive, making it more difficult to determine if some of the patient’s symptoms are correlated or not. A contrast brain MRI which includes a cine flow (cine-phase contrast) study can be helpful in determining the extent of compression and subsequent blockage of normal cerebrospinal fluid (CSF) flow throughout the craniocervical junction. A cervical MRI without contrast is also recommended to rule out a cervical syrinx (enlarged area in the center of the spinal cord), which can sometimes be associated with Chiari. If a cervical syrinx is found, an MRI of the remaining thoracic and lumbar spine should also be performed.

 

In general, Chiari malformation cerebellar tonsillar herniation is considered to be within normal anatomical variation in the following:
-First decade (0-10 years): 6mm or less
-Second and third decades (10-30 years): 5mm or less
-Fourth-eighth decades (30 to 80 years): 4mm or less
-Ninth decade (greater than 80 years): 3mm or less

 

Some mild or borderline Chiari malformations can be associated with extensive symptoms, while other times an extensive Chiari malformation is found, but the patient lacks any Chiari symptoms. So, a detailed history of symptoms including headache and associated features is crucial in determining whether a Chiari malformation is clinically relevant or not. This is more useful than basing treatment decisions purely on the extent of tonsillar herniation in Chiari. History is also important in excluding other disorders which can cause a reversible “pseudo-Chiari”, caused by a different disorder such as intracranial hypotension CSF leak, or low-pressure headache) or idiopathic intracranial hypertension (IIH) (previously known as pseudotumor cerebri).

 

According to the International Classification of Headache Disorders 3rd Edition (ICHD3), Chiari headache caused by Chiari type I malformation is usually occipital or suboccipital, of short duration (less than 5 minutes) and provoked by cough or other Valsalva-like maneuvers (straining in the abdominal region such as when having a bowel movement). It remits after the successful treatment of the Chiari malformation.

 

Diagnostic criteria require Chiari malformation to have at least two of the following:

1. Either or both of the following:
a) Headache has developed in temporal relation to the Chiari or led to its discovery
b) Headache has resolved within 3 months after successful treatment of the Chiari

 

2. Headache has one or more of the following three characteristics:
a) Precipitated by cough or other Valsalva-like maneuver
b) Occipital or suboccipital location
c) Lasting less than 5 minutes

 

3. Headache is associated with other symptoms and/or clinical signs of brainstem, cerebellar, lower cranial nerve and/or cervical spinal cord dysfunction. (These may include symptoms such as hoarseness, slurred speech, swallowing or choking difficulty, unsteadiness, dizziness, vertigo, tongue weakness, trigeminal or glossopharyngeal neuralgia, tinnitus, absent gag reflex, facial numbness, autonomic symptoms (syncope, slow heart rate (bradycardia), drop attacks), loss of pain and temperature sensation of the upper torso and arms (from syrinx), loss of muscle strength in the hands and arms (from syrinx)

 

According to ICHD3 criteria, diagnosis of Chiari malformation by MRI requires a 5-mm caudal descent of the cerebellar tonsils or 3-mm caudal descent of the cerebellar tonsils plus crowding of the subarachnoid space at the craniocervical junction as evidenced by compression of the CSF spaces posterior and lateral to the cerebellum, or reduced height of the supraocciput, or increased slope of the tentorium, or kinking of the medulla oblongata.

 

Unfortunately, we see many patients who have had Chiari decompression, but they continue to have chronic daily headache which often resembles their pre-surgery headaches. When you delve deeper into their pre-existing headaches, many times they describe headaches which had/have migrainous features (throbbing, pounding, pulsating pain quality with nausea (+/- vomiting) and/or photophobia and phonophobia (sensitivity to bright light and loud sound with bad headache flares)). These pre-surgical headaches often fit criteria for chronic migraine, many times of which were likely sustained as chronic daily headache and chronic migraine due to medication overuse headache (rebound). So, if any of the history is suggestive of a migrainous component, this should empirically treated for first to ensure they won’t get a cranial surgery/decompression simply for chronic migraine! With that said, if it is an obvious prominent Chiari with clear Chiari headache type symptoms, this can certainly expedite the treatment plan.

 

Most of the time, the chronic daily headaches that patients continue to have after decompression surgery are associated with some variable degree of these migrainous characteristics. They typically resemble a chronic migraine pattern, and many times treating the headaches as chronic migraine rather than being distracted and treating only as ongoing Chiari headache can provide significant improvement. If the Chiari has been decompressed, then it is certainly no longer a “Chiari headache” at that point, and treatment and diagnoses should be reconsidered. However, as mentioned above, even more important is screening for these migrainous features prior to surgery, and if present, treatments targeting migraine and chronic migraine should always be exhausted first because pure Chiari headache is not going to cause migrainous features of throbbing, pounding, pulsating headache with nausea (+/- vomiting) and/or photophobia and phonophobia. Pure Chiari headache just doesn’t cause those symptoms. Those symptoms are migraine. It is common that patients can have both Chiari and migraine. The key is differentiating which is which and eliminating the migrainous component to get more clarity of how much of the symptoms are truly Chiari related, if any.

 

In addition to a chronic migraine appearing headache, patients who have had Chiari decompression frequently have associated occipital neuralgia in the back of the head and a component of chronic post-craniotomy headache. This is related to scarring of the tissues in the back of the head and base of the skull where the occipital nerves travel. This scarring can pull, twist, and tangle up the occipital nerves over time which causes persistent occipital pain in the back of the head. Post-craniotomy headache is technically similar to chronic post-traumatic headache since decompression surgery is, well, certainly a form of trauma to the head. Chronic post-traumatic headache itself commonly has a chronic migraine clinical appearance (with or without pre-existing migraine history), and treating as such can often be very beneficial. For example, we often seen concussion patients that develop chronic daily headache and chronic migraine which is “turned on” by the injury or head trauma.

 

Successful treatment with significant improvement of chronic daily headache with chronic migraine characteristics following Chiari decompression surgery is often a difficult task requiring patience and a good headache specialist. Daily medications used in migraine prevention should be considered, particularly ones that are good for not only migraine, but also occipital neuralgia and musculoskeletal pain such as anticonvulsants (topiramate, gabapentin, etc.), TCAs (amitriptyline, nortriptyline), or SNRIs (duloxetine, venlafaxine ER). Neck physical therapy can often be very helpful at stretching out the suboccipital tissues and lessening tension on the occipital nerves. If there are any migraine or chronic migraine features, then more aggressive migraine preventives such as Botox (OnabotulinumtoxinA) injections or the CGRP monoclonal antibodies should also be considered. As of 2010, Botox is still the only truly FDA approved treatment for “chronic migraine”, although all of the other treatments are still used for it as well. It should be done according to the “PREEMPT protocol”. I prefer to do additional dosing over the occipital nerves and often add numbing medicine such as bupivicaine which can provide additional temporary relief as the Botox starts to kick in over the next couple weeks. If there is an ongoing chronic daily headache driver from rebound headache (medication overuse headache), it is also crucial to eliminate this factor. Improvement will not happen while this is an ongoing factor (especially if there is a chronic migraine component). If there are migrainous features to headache exacerbations, then using more migraine specific abortive (as-needed) meds such as triptans, gepants (such as Nurtec or Ubrelvy) or ditans (Reyvow) should also be considered. Notably, the gepants do not cause medication overuse headache (rebound headache).

 

IF YOU HAVE HEADACHE, MIGRAINE, OR FACIAL PAIN AND ARE LOOKING FOR ANSWERS ON ANYTHING RELATED TO IT, A HEADACHE SPECIALIST IS HERE TO HELP, FOR FREE!

FIRST, LET’S DECIDE WHERE TO START:

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR THE LATEST INFORMATION, HOT TOPICS, AND TREATMENT TIPS, VISIT OUR FREE BLOG OF HOT TOPICS AND HEADACHE TIPS HERE. THIS IS WHERE I WRITE AND CONDENSE A BROAD VARIETY OF COMMON AND COMPLEX  MIGRAINE AND HEADACHE RELATED TOPICS INTO THE IMPORTANT FACTS AND HIGHLIGHTS YOU NEED TO KNOW, ALONG WITH PROVIDING FIRST HAND CLINICAL EXPERIENCE FROM THE PERSPECTIVE OF A HEADACHE SPECIALIST.

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR A LIST OF POSSIBLE DIAGNOSES BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN DIAGNOSTIC TOOL DEVELOPED BY A HEADACHE SPECIALIST NEUROLOGIST HERE!

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR FURTHER EDUCATION AND SELF-RESEARCH ON YOUR DIAGNOSIS, VISIT OUR FREE EDUCATION CENTER HERE.

 

IF YOU HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING TO ASK QUESTIONS TO A HEADACHE SPECIALIST OR OTHER HEADACHE, MIGRAINE, AND FACIAL PAIN WEBSITE MEMBERS, VISIT OUR FREE DISCUSSION FORUMS HERE.

 

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Posted by on 5:38 pm in Migraine treatments | Comments Off on BOTOX (OnabotulinumtoxinA) FOR CHRONIC MIGRAINE; THE MOST EFFECTIVE PATTERN, TECHNIQUE, AND EVERYTHING YOU NEED TO KNOW. NOT ALL BOTOX TREATMENTS ARE CREATED EQUAL.

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Posted by on 8:55 pm in Migraine, headache, and facial pain tips | Comments Off on STOP LETTING YOUR CHRONIC MIGRAINE AND CHRONIC PAIN DEFINE YOU AND YOUR BRAIN PLASTICITY.

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