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Last updated on January 1st, 2021 at 05:04 am

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WHAT A PAIN IN THE BACK OF THE HEAD! OCCIPITAL NEURALGIA, TREATMENTS, AND TECHNIQUE FOR OCCIPITAL NERVE BLOCK.

@Neuralgroover

 

Background

Occipital neuralgia is a miserable nagging soreness and pain in the back of the head. I tell patients to think of occipital neuralgia as “sciatica of the head”. It is typically felt in the suboccipital region (where the base of the skull meets the top of the neck) and radiates variably into the back and top of the head and behind the ears. It can less commonly even radiate to the frontal areas (by the trigeminocervical circuitry in the upper cervical spinal cord and brainstem). It can be one sided or both sides. The pain is often described as an intense stabbing, sharp, shooting, shocking, or burning pain. It often occurs in attacks of pain which may last seconds to minutes, but can also be a continuous unrelenting pain. Sometimes it may not be as intense and may be a lower-level pain such as pressure, aching, soreness or throbbiness. The back of the head often feels very sore or tender. The pain and tenderness often increases by pushing on the back of the head and along the skull base, or lying on the back of the head. Some patients may have a sensation of numbness or tingling in the back of the head. Associated neck pain is typically in the mix too.

 

The cause of occipital neuralgia is most commonly idiopathic, meaning there isn’t a specific cause. If you have had surgery or an injury to the back of the head, this can cause 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. Sometimes the cause can be from a lot of arthritis in the upper cervical spine, tight muscles through the upper neck and skull base, or following a viral illness which can cause them to become inflamed.

 

Although patients often have isolated occipital neuralgia, I see many patients with occipital neuralgia who also have associated migraine and chronic migraine. This always creates an even more miserable feedback loop between frequent exacerbations of both the occipital neuralgia and migraine. The reason is because these two headache types influence and feed into each other. For example, 70% of patients with straightforward episodic migraine will get neck pain and tightness at the beginning of a migraine attack. So, if someone is stuck in a smoldering cycle of chronic migraine (15-30 days per month), neck pain and occipital neuralgia are commonly associated. The flip side is if someone has structural abnormalities in the cervical spine (herniated disc, injury, whiplash, etc.), it can also be a contributor to frequent or daily headaches (especially if they have a history of migraine).

 

Treatment

Neck physical therapy should always be considered as a first line treatment. The goal is to stretch out and loosen the muscles below the skull base and neck. The occipital nerves pierce directly through these muscles as they travel to the back of the scalp. So imagine what is happening to those nerves if these muscles are in a state of constant tightness and spasm. The muscles will continually squeeze and irritate the nerves traveling through them, which keeps them irritated and keeps the pain going.

 

Along with the neck physical therapy, I typically suggest a daily preventive medication until the patient is consistently doing much better for several months. A more detailed list of commonly used medications specific for occipital neuralgia can be read here. In general, typical first line options are the anticonvulsants with Gabapentin (Neurontin) being a first line medication, or the antidepressant/anxiety class of medications, with the most effective ones being Amitriptyline (Elavil), Nortriptyline (Pamelor), Duloxetine (Cymbalta) and Venlafaxine XR (Effexor XR).

 

If there is associated chronic migraine or frequent migraine, a migraine preventive medication or treatment should be chosen, optimally one that can be helpful for both disorders. Preventive migraine treatments include daily pills, CGRP monoclonal antibodies (mAbs), neuromodulation devices, and Botox injections. Botox injections in particular are a great consideration for the combination of chronic migraine and occipital neuralgia because it can be very effective for both. I always give additional dosing over the occipital nerves in this scenario.

 

If there is a migraine component (as there often is), it’s always important to make sure to have a good abortive option for migraine exacerbations. NSAIDs (non-steroidal anti-inflammatory drugs) can be helpful for both migraine and the occipital neuralgia component. Diclofenac potassium tends to be one that I prefer, but some people do better with one or another, so it can be a trial-and-error process. If NSAIDs are not effective for aborting the migraine, then a more migraine specific option should be used such as a triptan, one of the new gepant options such as Nurtec ODT (Rimegepant) or Ubrelvy (Ubrogepant), or the new ditan medication Reyvow (Lasmiditan). A neuromodulation device could also be considered.

 

Other treatment options include occipital nerve blocks, occipital nerve stimulators, and occipital nerve decompression to detangle the occipital nerves through the scalp tissue. Most centers have moved away from occipital nerve stimulators since insurance rarely covers them and there are common problems with lead migration (leads move out of place) or lead infection. If there is a strong cervicogenic component along with the occipital neuralgia, pain management procedures such as cervical facet blocks can also be helpful. However, if the patient has only occipital neuralgia and not much of a neck pain component, cervical facet blocks and other procedures targeting the cervical spine are typically not helpful.

 

Occipital Nerve Blocks

Occipital nerve blocks should also be considered and offered. They are easy to perform in the office, can provide quick dramatic relief, and only take a minute or so to do. These can act as both an abortive option to cool down an ongoing flare of both migraine and occipital neuralgia. It can also help to prevent the pain returning for a period of time, or making it much more tolerable. However, they are typically more of a temporary benefit (days to weeks to months). However, I have quite a few patients that can get 3 months of relief until they wear off. I have occasionally seen patients break the cycle of occipital neuralgia for much longer, or even indefinitely, but this should not be the expectation. Unfortunately, it is hard to predict how much benefit one may have, or how long it may last. Pain relief typically occurs rapidly, often within minutes of the procedure, but full benefit should be seen by 2-3 days. There may or may not be some associated temporary numbness in the back of the scalp for part of the day as well. If they are done with steroids, they should not be repeated at intervals any less than 3 months. If they are done without steroids, there is no limitation on how frequent they can be done.

 

For these injections, I prefer to have the patient sitting up on the exam table with their legs hanging over 1 side. Some physicians have them sit backwards on a chair, resting their arms and head on the back of the chair. I stand on the opposite side of the exam table behind them. These are done with an anesthetic (numbing) medication such as Bupivacaine, Lidocaine, or Ropivacaine. Some physicians combine these injections with a steroid, most commonly Triamcinolone (Kenalog) or Betamethasone (Celestone). The existing evidence suggests steroids do not add much value to occipital nerve blocks, unless they are done for cluster headache. However, anecdotally many physicians still feel patients tend to do better with steroids, which makes sense given the inflammatory component of occipital neuralgia and potent anti-inflammatory effect of steroids. I prefer to use a small ½ inch 30-gauge needle (same as for Botox) to minimize the temporary pain of injection, although it takes a bit more force to inject the medicine through the needle.

 

I prefer to do 3 injections per side of occipital neuralgia (or both sides if both are affected) to ensure the occipital nerve is treated at all major points. These spots are illustrated on the photograph below. Some physicians do only 1 or 2, so this varies between physicians. The 1st injection site is located by feeling the occipital protuberance, or inion, (bump in the middle along the skull base), and going 2 fingerbreadths down and 1 over. This is the region where the greater occipital nerve pierces through the musculature. The 2nd injection site is located just lateral to the occipital protuberance, about 1/3rd of the way over between the occipital protuberance and the mastoid process behind the ear. Feel for a small groove in this area. This is the occipital groove, or notch, where the occipital nerve travels. The patient typically has the most tenderness over this spot as well, so it is typically quite easy to find. The occipital nerve travels along side the occipital artery, so it’s important to withdraw the syringe in this location, as well as all locations, prior to injection to ensure there is no blood retraction into the syringe. The 3rd site is located just behind the ear, posterior to the mastoid bone in another palpable groove. This also happens to be where the lesser occipital nerve travels.

 

Side effects of occipital nerve blocks are typically minimal and well tolerated. There are no limitations to activity afterwards and they will not make you drowsy. Some temporary tenderness in the sites is possible. Dizziness and nausea are infrequent brief side effects. Some patients can develop slight divots in the area of injection if steroids are used. If steroids are used, some patients can also feel more energized for a couple days, and sometimes some flushing.

 

Here is an example of how I do a typical bilateral (both sides) occipital nerve block procedure (following discussion of risks, benefits, alternatives, informed consent, etc.). If only one side is done, dosing can be split in two.

 

Procedure

A combination of Triamcinolone (Kenalog) 40 mg (1 cc) OR Betamethasone (Celestone) 6 mg (1 cc) and 9 cc of 0.25% Bupivacaine was prepared in a single syringe and the injection sites were sterilized with alcohol swabs.

For both sides, the greater occipital nerve was injected 3 cm caudal and 1.5 cm lateral to the inion where the main trunk of the occipital nerve penetrates the semispinalis muscle. The needle was placed perpendicular and the needle advanced 1 cm. After aspiration to ensure no obstruction or presence of blood, the area was injected with 2 cc. The needle was then repositioned at the greater occipital nerve at the level of the occipital groove. After aspiration to ensure no obstruction or presence of blood, the area was injected with 2 cc.

For both sides, the needle was repositioned at the posterior border of the sternocleidomastoid at the level of the angle of the jaw, where the lesser occipital nerve is located. After aspiration to ensure no obstruction or presence of blood, the area was injected with 1 cc.

 

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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 15th, 2021 at 05:21 pm

SYNCOPE EPISODE, SYNCOPE DEFINITION, AND AN EASY TOOL TO QUICKLY RECALL ALL CAUSES OF SYNCOPE.

@Neuralgroover

If you have ever had a syncope episode (passing out, or fainting), you know how scary it can be. It is scary not only from the event itself, but sorting out the causes of syncope can be both scary and frustrating. Syncope is not an uncommon association with migraine attacks. This is most often due to a vasovagal response related to the severe pain of the migraine or dehydration from vomiting. However, many migraineurs can also have some degree of dysautonomia during an attack. Dysautonomia is a dysfunction of the autonomic nervous system, which controls blood pressure, arterial dilation or constriction, heart rate, heart rhythm, sweating, and gastric motility. This is illustrated with migraine associated symptoms such as gastroparesis, dizziness, POTS, and complaints of cold hands and feet during an attack for some.

 

So what is syncope? Let’s first discuss the syncope definition, which is also frequently termed syncope and collapse. Syncope is a temporary loss of consciousness typically due to a brief lack of blood flow to the brain. The most common reasons are from a drop in blood pressure upon standing (orthostatic hypotension), from a vasovagal response (a form of neurocardiogenic syncope), or from the heart not pumping enough blood to the brain from an arrythmia (heart temporarily beating too fast or too low), or a weak heart muscle (such as in congestive heart failure). Near syncope is the term for “almost” having a syncope episode. This is where you feel like you “almost pass out”, and perhaps briefly get dizzy, lightheaded, woozy, and unsteady.

 

Syncope is rarely ever of a true neurologic cause. However, for some reason, this is still one of the most common reasons for neurology consults in the hospital setting. Therefore, I created a simple mnemonic tool that will help you consistently remember every possible cause of syncope to check off your differential diagnosis list of possibilities. I always teach this tool to the residents and medical students who are rotating on the inpatient neurology hospital service because syncope is such a common reason for neurological consultation. However, it can be helpful across all medical specialties since syncope is such a common event across all specialties. It can also be used by patients suffering from syncope to help them gain a better understanding of syncope and syncope causes.

 

The mnemonic tool is CONSNOC. It’s a palindrome spelled the same forwards and backwards. It’s a nonsensical word, but remembering it will quickly bring to memory every possible differential diagnosis of syncope to run through in your mind. Let’s go through each letter:

 

Cardiac: Think the SA (sinoatrial) node, and then think Structural and Arrhythmia causes. Structural can be outflow obstruction or low ejection fraction in CHF (congestive heart failure). Arrhythmia can be from the heart beating too fast (tachycardia) or too slow (bradycardia).

 

Orthostatic: This is from low blood pressure which occurs when someone stands up from a lying or sitting position. It is often seen with dehydration or blood pressure medication doses that are too high. Orthostatic intolerance is another term for this. Since this is typically such a common cause of syncope, near syncope, and dizziness, I have listed a number of treatment suggestions to help with treatment at the bottom of this page.

 

Neurocardiogenic: This is your classic vasovagal response where there is a sudden decrease in heart rate followed by an abrupt drop in blood pressure leading to syncope and collapse (passing out, or fainting). The physiologic mechanism for neurocardiogenic syncope can be triggered by several things. Vasovagal syncope classically occurs with a sudden scare (sees blood, intense pain, fright, etc.). Variants of the vasovagal response also include micturition or defecation syncope (think about the old lady who passed out after standing up from using the toilet, triggered by a large parasympathetic discharge), carotid hypersensitivity (think about the old guy shaving and becomes bradycardic by inadvertent carotid massage from pressing on the neck during shaving), and cough syncope or syncope with coughing.

 

Seizure: This is a common reason for inpatient neurological consult even though syncopal episodes are almost never from a seizure. Look for additional symptoms such as tongue biting, incontinence, and witnesses to the event for description (preceded by staring off, posturing, tonic-clonic activity, etc.). Keep in mind, you can still have convulsions during syncope called convulsive syncope (syncope with convulsions), which are not true seizures but just a manifestation of sudden drop in blood pressure and lack of blood flow to the brain. Incontinence can also occur with syncope, so it does not confirm a seizure cause. The diagnosis of seizure is best made by the company it keeps (associated symptoms with the syncopal event).

 

Neuropathic: This correlates to dysautonomia, also known as autonomic neuropathy. This is neuropathy involving the small nerve fibers that control heart rate, heart rhythm, blood pressure, gastrointestinal motility, sweating, and other things. The result is often a disconnect between blood pressure and heart rate where they are not working in synchronicity together, leading to symptoms such as syncope. There are a wide variety of these disorders, but the top categories to keep in mind are from chronic/toxic autonomic neuropathy such as from diabetes, autoimmune dysautonomia (such as acetylcholine receptor (AchR) autoantibody, paraneoplastic), post-viral dysautonomia, neurodegenerative dysautonomia (such as Shy-Drager Syndrome in Parkinson’s Disease), and POTS (Postural Orthostatic Tachycardia Syndrome). These disorders are often easily diagnosed by a tilt table test, or even a good set of orthostatic vitals.

 

Other: Think additional possibilities such as mechanical (the patient simply tripped or lost their footing), glucose (hyperglycemia, hypoglycemia)

 

Cerebrovascular: Think posterior circulation and vertebrobasilar ischemia. This is the other most common reason for inpatient neurology consultation in terms of TIA (transient ischemic attack) or stroke, but again, syncope is rarely the result of this. If this is the cause, it is typically associated with other neurological symptoms, particularly of the posterior circulation. So, assess for associated brainstem symptoms such as double vision, hemiparesis or hemisensory loss, slurred speech, vertigo, dysphagia, etc. Similar to seizures, the diagnosis of posterior circulation TIA or stroke is best made by the company it keeps (associated symptoms with the syncopal event).

 

As mentioned above, since orthostatic intolerance (orthostasis) is such a common symptom and disorder, here are some suggestions to consider to help treat it.

Guidelines for the Treatment of Orthostatic Intolerance (OI):

 

  1.  Make all postural changes from lying to sitting or sitting to standing, slowly.

 

  1.  Drink to 2.0 -2.5 L of fluids per day. If you have a history of congestive heart failure (CHF), you should discuss fluid intake with your cardiologist to avoid a CHF exacerbation.

 

  1.  Increase sodium (salt) in the diet to 3 – 5 g per day. If not helpful and blood pressure is stable, may try 5-7 g per day. If you have a history of high blood pressure, you should discuss these adjustments with your cardiologist or primary care physician.

 

  1.  Avoid large meals which can cause low blood pressure during digestion. It is better to eat smaller meals more often than three large meals.

 

  1.  Avoid alcohol.  Alcohol and cause blood to pool in the legs which may worsen low blood pressure reactions when standing.  This can aggravate OI.

 

  1.  Perform lower extremity exercises to improve strength of the leg muscles.  This will help prevent blood from a pooling in the legs when standing and walking.

 

  1.  Raise the head of the bed by 6 to 10 inches.  The entire bed must be at an angle.  Raising only the head portion of the bed at waist level or using pillows will not be effective.  Raising the head of the bed will reduce urine formation overnight and there will be more volume in the circulation in the morning.

 

  1.  During bad days, drink 500 cc of water quickly.  This will result in an increased blood pressure within 5 minutes of drinking the water.  The effect will last up to one hour and may improve orthostatic intolerance.

 

  1.  Use custom fitted elastic support stockings.  These will reduce a tendency for blood to pool in the legs when standing and may improve orthostatic intolerance.

 

  1.  Use physical counter maneuvers such as leg crossing, squatting, or raising and resting the leg on a chair.  These maneuvers increase blood pressure and can improve orthostatic intolerance.

 

  1. Avoid temperature extremes, particularly excessive heat.

 

  1. For activity planning involving higher levels of physical activity, try to plan for:

-Before rather than after a meal

-Afternoon rather than morning

-Avoid excess heavy lifting

-Avoid during excessively hot weather

 

 

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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:46 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:47 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:48 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. Mild transient headache from the Covid-19 vaccine is also being reported for some patients.

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 mindfulness techniques such as yoga and medication, diet, hydration, proper sleep and exercise certainly play a role. You’ll want to ensure you have a consistently effective well tolerated abortive/acute (as needed) migraine specific treatment such as the new gepant (Nurtec and Ubrelvy) or ditan (Reyvow) optionstriptans, neuromodulatory device, or other abortive option. 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 (Aimovig, Ajovy, Emgality, Vyepti), 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.

Covid headache may also be associated with a variety of Covid-19 neurological symptoms. Patients with COVID-19 headache (or without headache) include loss of taste and/or smell, dizziness, muscle weakness, sensory disturbances such as tingling or numbness in the hands and feet, confusion, delirium, persistent neurocognitive symptoms (memory, concentration, attention, etc.), stroke (seen in many young patients as well as older), and seizures.

Now that the Covid-19 vaccine is available, Covid-19 vaccine side effects are reported in some patients, including headaches. However, the Covid-19 vaccine headaches are typically mild and a temporary side effect. The Covid-19 vaccine side effects of headaches are typically associated with other common transient side effects of some vaccinations (fevers, chills, body aches, fatigue, exhaustion, soreness at injection site), which are just a sign of your body mounting an immune response in preparation for potential Covid-19 exposure and infection. Regardless, Covid-19 vaccination headache, if present, is milder and of shorter duration than Covid headache from the direct infection itself.

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. For many patients, treatment of Covid-19 headache and the infection itself revolves around symptomatic treatment such as rest, hydration, over the counter common cold and virus type medications (analgesics, decongestants, etc.), and vitamins such as vitamin C, zinc, and vitamin D. Symptomatic treatment 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).

However, treatment may also include intravenous medications such as steroids (typically dexamethasone), Remdesivir, and supplemental oxygen, especially for more serious infections. Intravenous antibiotics may also be necessary if the Covid-19 infection progresses to pneumonia, in which bacterial infections begin within the inflamed and injured lung tissue from the Covid-19 infection. There have also been conflicting reports of Covid-19 treatment success with Hydroxychloroquine and Ivermectin, but these are not currently listed in the standard treatment guidelines. Any Covid-19 infection should be evaluated and managed by your doctor to ensure you are optimizing your treatment strategy to prevent progression to pneumonia or other Covid-19 complications. Your treatment may vary depending on the infection severity, your medical history and risk factors for more severe disease, guidelines, and your doctor’s treatment preferences and experience. So, you should see your doctor or local emergency department if you have any symptoms or concern for Covid-19 infection because early treatment is crucial.

If the headaches have migraine features, they can be treated as migraine, tension-type headache, or NDPH with acute/abortive options as detailed above, and preventive daily treatment options, also as detailed above, if the frequency of headaches remains high and is not improving.

Covid-19 vaccination is also recommended in order to prevent infection, as well as prevention of Covid headache and Covid neurologic symptoms.

 

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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:49 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:50 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

 

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Last updated on January 14th, 2021 at 10:51 pm

BEST HEADACHE AND MIGRAINE PREVENTION MEDS AND TREATMENTS, WHEN YOU SHOULD START ONE, AND WHEN YOU SHOULD 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.

So this blog will focus on migraine preventive meds and treatments, which are a continuous treatment such as a daily pill or a monthly/quarterly treatment such as CGRP mAbs, all of which are detailed below. The goal of migraine preventive treatment is to lessen the frequency and/or severity of migraine attacks. This is in contrast to migraine abortive/acute (as needed) options such as triptans, gepants and ditans. The goal of migraine abortive treatments is to stop individual migraine attacks at onset so the migraine does not reach full severity, ends quickly, and your function is restored and maintained rather than having to go lay down and miss the whole day in bed.  If you have migraine, you want to have both a good abortive and preventive treatment plan to lessen migraine’s nasty habit of interfering and disrupting life and function.

 

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 migraine treatments with supplements which have evidence for migraine prevention, and those are detailed and discussed here.

 

So, let’s discuss migraine prevention medicine.  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 75 mg). So these will open up another new class of preventive migraine medications engineered purely for migraine treatment! Notably, Biohaven submitted a request to the FDA in October 2020 to approve Rimegepant as a preventive migraine treatment, in addition to its current migraine abortive FDA approved indication. This decision is pending. This move followed clinical trials showing that patients taking 75 mg of Rimegepant every other day experienced a 4.3 day reduction from baseline in monthly migraine days.

 

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. Women who are on oral contraceptive pills are often warned prematurely by their pharmacist that Topiramate will effect their oral contraceptive. This is partly true. Topiramate at a daily dose of 200 mg or less does not interact with oral contraceptives according to this study, but it can at higher doses which could potentially decrease effectiveness. However, the goal dose for effective migraine prevention is typically 100 mg per day, well below that 200 mg dose that could impact effectiveness of the oral contraceptive. I 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

-Pregnancy: This one is tricky since the goal during pregnancy is to minimize the use of as many medications as possible. Mindfulness treatments such as yoga and meditation are always good recommendations. With that said, the first line option we typically begin with is magnesium supplementation of 400-800 mg daily. If a prescription medication is needed, cyproheptadine 4 mg at bedtime has been a long time medicine used in this scenario, and it can be titrated to 4 mg three times daily if needed. The good thing with pregnancy is that migraines improve in about 2/3rd of women (especially 2nd and 3rd trimester), and it is not uncommon to hear that migraines resolved during pregnancy. So many times a preventive treatment may not even be needed. For menstrually related migraine outside of pregnancy, further discussions and treatment considerations can be read here.

-Epilepsy: Topiramate, Topiramate ER/XR (extended release), Divalproex, Carbamazepine, and Zonisamide are the anticonvulsant medications we see most useful for migraine prevention. In fact, Topiramate and Divalproex are also FDA approved for migraine prevention. If patients 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. Women who are on oral contraceptive pills are often warned prematurely by their pharmacist that Topiramate will effect their oral contraceptive. This is partly true. Topiramate at a daily dose of 200 mg or less does not interact with oral contraceptives according to this study, but it can at higher doses which could potentially decrease effectiveness. However, the goal dose for effective migraine prevention is typically 100 mg per day, well below that 200 mg dose that could impact effectiveness of the oral contraceptive.

-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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:52 pm

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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:53 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:55 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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 January 14th, 2021 at 10:56 pm

MENSTRUAL MIGRAINE TREATMENT TIPS AND CONTRACEPTION STROKE RISK.

@Neuralgroover

BACKGROUND

Pure menstrual migraine and menstrually-related migraine are very common 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 menstrually-related migraine (migraines during menses and outside of menses) and pure menstrual migraine (migraines during menses only). What is the best menstrual migraine treatment?

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.

So what is the connection with contraception, migraine, and stroke (and similar terms floating around such as migraine stroke, migraine with stroke, migraine with aura stroke, ocular migraine stroke, stroke migraine, and aura migraine stroke)? We will get to those answers and more a little further down.

 

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) for the treatment for menstrual migraine to discuss with your doctor to treat 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 POSSIBLE TYPES OF HEADACHES OR FACIAL PAINS BASED ON YOUR SYMPTOMS, USE THE FREE HEADACHE AND FACIAL PAIN SYMPTOM CHECKER 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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