Migraine Treatments


Last updated on April 10th, 2021 at 05:34 am

MIGRAINE HEADACHES EXPLAINED.

@Neuralgroover

Migraines are a very intense type of headache that are often accompanied by other symptoms, including nausea, vomiting, sensitivity to light and sound, as well as neurological symptoms such as visual disturbances, numbness or tingling, speech disturbances (slurred speech, difficulty getting words out), weakness, vertigo, cognitive dysfunction or “cognitive fog”, among other things. Migraines tend to be more prevalent in women than in men, with a 3:1 ratio. A common risk factor for migraines often involves family history, but not for everyone.  People who suffer from migraines report intense feelings of pain, including a pulsating/throbbing sensation. This often occurs on 1 side of the head, but can also involve both sides. Exercise and activity during a migraine will often make it worse. Migraine is usually associated with nausea, and/or sensitivity to light (photophobia) and sound (phonophobia)  Migraines often come in different phases, which are called prodrome, aura, the headache phase, and postodome, but not everyone gets all 4 phases:

  • The prodromal phase of a migraine often marks the beginning of a migraine attack and can happen over a period of a few hours ranging to a few days. Some of the symptoms include irritability and depression; food cravings; yawning and tiredness; and fatigue or muscle stiffness. Some patients report their prodrome as just a difficult to describe feeling that they recognize as an early warning sign of an impending migraine. Not every migraine attack includes the prodromal phase.
  • The aura phase of a migraine doesn’t necessarily always happen in every migraine attack, and only about 25% of patients with migraine get aura. Historically, those that get aura are called “classical migraine”, whereas “common migraine” refers to the more common variety of migraine which isn’t associated with aura. A large number of people who have migraines report that during the aura phase, they experience loss of sight, numbness, and other symptoms. Visual aura (loss of vision, jagged lines, flashing, colors, shapes, wavy lines, kaleidoscope, shimmering, expanding blind spot, etc.) are the most common aura. This is followed by numbness and tingling on 1 side (especially face and arm), and then dysphasia (trouble speaking; slurred speech, getting words out). There are also less common types of aura such as hemiplegic migraine aura (1-sided weakness), and brainstem aura (previously called “basilar migraine”; slurred speech, vertigo, tinnitus, double vision, hearing impairment, decreased level of consciousness, ataxia/imbalance). The aura phase should last between 5-60 minutes per ICHD3 criteria. Hemiplegic migraine can be associated with 1-sided weakness which can last up to 3 days. If the other types of aura last longer than 60 minutes, it is called prolonged or atypical aura, and usually warrants a brain CT or MRI, although it is not too uncommon to see. .
  • The headache phase of a migraine is often the longest and most intense period of a migraine. Symptoms include intensive throbbing, nausea, giddiness, irritability, stiffness, and soreness. According to ICHD3 criteria, an untreated or unsuccessfully treated migraine attack should last 4-72 hours. A headache lasting longer than 72 hours (3 days) is called status migrainosus. It is not uncommon for a refractory migraine to last days and sometimes weeks for some patients.
  • The postdrome phase is the drawing down of a migraine attack. It can last for up to 48 hours and some of the lingering symptoms remain from the other phases of a migraine attack. Patients often report feeling wiped out, fatigued, and sore as if they were “hit by a bus”.

 

According to the American Migraine Foundation, more than 36 million people suffer from migraines (although now estimated to be closer to 39 million), but only one out of three people actually talk to their doctors about their pain.

Statistics About Migraines and Their Prevalence

According to several different sources, migraines are one of the most common types of illness in the world. More specifically, it is ranked as the 3rd most prevalent illness in the world. It is estimated that migraine affects about 39 million Americans, and 1 billion worldwide. For example, 1 in 4 households in the United States have an individual that suffers from migraine attacks. Migraines impact 18-20% of women (1 in 5) and 6% of men (1 in 16) in the United States and they are also fairly common in children.

Migraines are also a common cause for an emergency room visit. In fact, there are more than 1.2 million emergency room visits each year in the United States for someone who is suffering from an acute migraine attack. Patients with migraine have a greater than 1.5 fold increase in office visits, and a greater than 2 fold increase in ER visits and hospital admissions. Migraines can also diminish the quality of life for the people who suffer from them. More than 4 million adults suffer from chronic migraine pain, which is an individual who is experiencing more than 15 days of migraine pain each month. Approximately 3% of patients will transform from episodic migraine to chronic migraine each year. Overall, it is estimated that 3-5% of patients in the United States have chronic migraine. Also, 20% of people who suffer from chronic migraines are disabled. Disability due to migraine peaks between the ages of 15-49 years old, which are peak employment years. Thus, migraine now accounts for the 2nd leading cause of years lived with disability following low back pain! Migraine also accounts for 50% of all neurologic disability. All of this puts a very high price tag on migraine, with an estimated 36 billion dollars spent in migraine costs in the United States each year.

 

Migraines in Children

Migraines are commonly undiagnosed in children. They are more commonplace in adolescent children, but 10% of school-age children suffer from migraines. Half of all migraine sufferers have their first migraine attack before they turn twelve and if a child has one parent who suffers from migraines, they have a 50% chance of developing migraines during their lifetime. Also, boys under the age of twelve tend to have migraines more often than girls, but that trend reverses in adolescence, typically with onset of menarche (which also highlights the hormonal influence on migraine).

 

What Causes Migraines?

There are a number of reasons that people suffer from migraines, but the true cause of them is not fully understood. Genetics and environmental factors play a role. In fact, around ⅔ of migraine cases run in families. Migraines also tend to happen in people who are prone to stress, bipolar disorder, and depression. There are also some common triggers for migraines, including:

  • Drinks, such as alcohol and caffeinated beverages.
  • Work stress or stress at home.
  • Bright lights or strong smells.
  • Drastic changes in one’s sleep cycle.
  • Bouts of overexertion.
  • Changes in the weather or other barometric pressure changes
  • Certain foods and food additives such as MSG, nitrates, aspartame, and other substances such as artificial sweeteners.

 

Migraine Theories:

1) Vascular theory; “vascular headache” (outdated):

a) Lack of blood flow (ischemia) caused by vasoconstriction (narrowing) of the intracranial arteries (arteries inside the brain) caused migraine aura.

b) The vasoconstriction was then followed by rebound vasodilation (dilation) of the arteries. This dilation activated pain receptors on the arteries, and this was the cause of the pulsating headache.

c) This theory has since been disproven and outdated. Studies have also shown that the physical pulsations of the arteries did not correlate to the pulsating sensations of the headache pain.

2) Neurovascular theory (current):

a) Migraine is a neurogenic process with secondary changes in cerebral perfusion (related to neuronal dysfunction and hypometabolism during an attack). In other words, migraine is an electrical neurological event in the brain, not an event triggered by blood flow changes. This electrical event influences changes in brain metabolism such as hypometabolism and hypermetabolism. When the neurons are in a hypometabolism state, they have less oxygen and glucose requirement since they are not as active, and thus there is a lack of blood flow (not due to vasoconstriction of the brain arteries). This can be followed by hypermetabolism in which there is an increase in oxygen and glucose requirements and thus, increase in blood flow (so not necessarily simply rebound vasodilation).

 

b) Migraine aura is a good illustration of this phenomenon. Migraine aura is caused by an electrical wave spreading across the cortex of the brain moving at about 3 mm per minute (not by vasoconstriction as per the older vascular theory). At the front of this spreading electrical wave it causes hypermetabolism and an increase in blood flow. This hypermetabolism causes the “positive” migraine aura features (colors, flashing lights, kaleidoscope, shapes, zig-zags, tingling sensory changes, etc.). Following this electrical wave there is “neuronal depression” and hypometabolism, associated with a decrease in blood flow. This hypometabolism causes the “negative” migraine aura features (loss of vision, black spots, numbness, etc.). Depending on where this wave spreads, you may get different aura symptoms; visual aura as it spreads across the occipital (visual) cortex, sensory/numbness/tingling as it spreads across the parietal (sensory) cortex, dysphasia (trouble speaking, slurred speech) as it spreads across the frontotemporal (speech) cortex, one sided weakness in hemiplegic migraine as it spreads across the frontal (motor) cortex, brainstem symptoms such as vertigo, tinnitus, double vision, hearing loss, imbalance, decreased level of consciousness, slurred speech (previously called basilar migraine, now called migraine with brainstem aura) as it spreads across the brainstem.

 

c) The electrical event of migraine not only causes the changes in metabolism as described above, but the trigeminal nerves are also activated. Think of migraine as an electrical switch that gets turned on in the brainstem. It then turns on and activates the trigeminal nerves. The trigeminal nerves innervate all of the arteries in the brain and through the meninges surrounding the brain. When activated, the trigeminal nerves release a variety of inflammatory proteins (such as CGRP) and neuropeptides. The result of this is 3-fold:

1st, these inflammatory peptides cause neurogenic inflammation around the brain. Think of it like a sterile (non-infectious) meningitis. So, when you’re having a migraine, exercise and activity, moving around, bouncing in a car, etc. often worsen the pain.

2nd, it causes cerebral vasodilation in the brain and meninges. The dilation itself does not cause the pain, but rather it triggers the trigeminal nerves which innervate the arteries, and this sends signals back to the brain that something is going on, which in turn causes more release of inflammatory proteins and causes the migraine to worsen. This is the basis of why it is called the neurovascular theory of migraine.

3rd, it enhances and exaggerates the transmission of pain from the trigeminal nerves, into the brainstem, and into the cortex of the brain where the pain is recognized.

 

At baseline, a patient with migraine who is not having a headache always has a state of neuronal hyperexcitability in the cerebral cortex, especially in the occipital cortex (which is why the majority of aura symptoms tend to be visual aura). So, they have a much lower threshold to a migraine being activated and triggered as compared to someone without migraine. In other words, the neurological system in a patient with migraine can be thought of as always being in a hyperactive, hypersensitive, overdrive state with the “volume turned way up” compared to a person without migraine. Thus, I tell my patients the goal of preventive treatment is to “turn the volume down” and increase the threshold of migraine being triggered so easily.

 

What Are Some Common Treatments for Migraines?

There are two categories of treatment for any type of headache, including migraines. Migraines can be treated through abortive or preventive means. Abortive treatment for any type of headache includes medications such as aspirin, which treats the headache while it’s happening. Preventative treatments are intended to keep a headache or migraine from happening so frequently. Here are some of the different types of treatments for migraines.

 

Abortive Treatment for Migraines

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.  Over-the-counter pain relievers for migraines, such as aspirin or ibuprofen, are fairly commonplace. Some more aggressive abortive treatments include prescription medications like triptans (such as Maxalt) that block pain pathways within the brain. Some people may also receive anti-nausea drugs and opioid prescriptions to deal with more intense migraine symptoms. The migraine specific abortive/acute (as needed) treatments include triptansgepants (Ubrelvy, Nurtec), ditans (Reyvow) or neuromodulatory devices.

Preventative Treatments for Migraines

Medications that lower blood pressure, antidepressants, anti-seizure drugs, CGRP monoclonal antibodies, and even botox are some of the common preventative treatments for migraines. The classification of the preventive medicine typically has nothing to do with its purpose when it is used for migraine. For example, there are specific anti-blood pressure medicines that are good for migraine prevention. However, they do not work for migraine because of blood pressure changes, but rather they affect the electrical pathways of migraine. The same scenario goes for the antidepressant/anti-anxiety and anti-seizure categories. The medicines selected within each of these preventive categories are very specific and based on clinical trials and evidence. In other words, not all medicines within a specific medication class (such as all antidepressants) have evidence for migraine prevention, but rather very specific ones within that class. Medications that are designed to lower blood pressure can sometimes prevent migraines with aura and without aura. Certain types of antidepressants can help prevent migraines, but have some undesirable side effects in some individuals. Anti-seizure drugs, such as Topamax, can reduce the frequency of migraines in some individuals. The preventive migraine treatments should be used until the migraine and headache frequency is significantly improved consistently for several months. As mentioned above, this can be done with a variety of medications which may also include the CGRP monoclonal antibody (mAb) treatments (Aimovig, Ajovy, Emgality, Vyepti), Botox, natural supplements, herbals and vitamins, or neuromodulatory devices.

Alternative Treatments for Migraines

Some other types of treatment for migraines include acupuncture, cognitive behavioral therapy, supplements, essential oils, yoga, meditation, and other techniques designed to enhance relaxation. For some individuals, exercise can decrease the frequency of migraines. In fact, some studies have shown that a routine exercise program can be just as effective as some of the prescription preventive medications used for 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. There are also nutraceuticals and supplements which have good evidence for migraine prevention.

 

Finding Help For Migraines

Migraines remain a poorly understood medical condition, but there are treatments available. Only 4% of people suffering from migraines work with a headache specialist or a pain specialist. It is estimated that preventative treatment could benefit around 25% of people who suffer from severe migraines.

If you suspect that your headaches are migraines, you should see your doctor. Furthermore, any type of headache warrants at least one visit with your doctor to make sure there are no concerns by medical history or examination for any other worrisome causes of your headaches. They may refer you to a neurologist or other type of headache specialist. Oftentimes, a wide variety of tests may be given, including CT scans and MRIs, to see what is contributing to the cause of the migraine. The good news is that migraines can be successfully managed for the majority of patients, and that many people live with them thanks to the treatments that they receive.

 

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 April 8th, 2021 at 11:49 pm

FOODS THAT STOP NAUSEA IN ITS TRACKS – 2021.

@Neuralgroover

Nausea is an extremely common symptom across a wide spectrum of diseases. It is one of the main symptoms in the ICHD3 diagnostic criteria for migraine. Nausea is one of the 3 “most bothersome migraine symptoms” (along with photophobia (sensitivity to light) and phonophobia (sensitivity to sound)) which most acute/abortive (as-needed) migraine medication clinical research studies assess as a primary data endpoint in trying to resolve, because it is such a disruptive symptom.

 

As the electrical activity of migraine spreads through the brainstem, it activates the nausea centers of the brainstem, and you are well aware of the misery that follows that. So, are there tricks or things that you can do to lessen nausea other than using standard antiemetics (anti-nausea) medications such as Metoclopramide (Reglan), Prochlorperazine (Compazine), Promethazine (Phenergan), and Ondansetron (Zofran)? Are there certain foods or drinks that can help lessen the nausea? I’ll give you the quick answer which is detailed below. Yes there are!!

 

You may be searching terms such as, what helps with nausea, what helps nausea, how to get rid of a stomach ache, home remedy for nausea, home remedy for stomach ache, feeling nauseous, upset stomach remedies, nausea remedies, what to eat when stomach is upset, stomach upset remedy, stomach upset home remedies, how to help nausea, home remedies for stomach upset, how to get rid of stomach ache, home remedies for stomach ache, stomach ache remedies, best foods for nausea, etc., etc.

 

Let’s talk about how to treat nausea symptoms naturally…

 

Occasionally, Virtual Headache Specialist will allow guest bloggers to write an article on a migraine related topic. How to treat nausea including natural treatments for nausea is one of those very relevant migraine associated topics. It is certainly not a symptom associated only with migraine, and has a very wide range of causes. Whatever the cause may be, it is a miserable symptom to have to deal with. So, I hope the following article gives you some additional firepower to add to your migraine treatment war chest in treating the migraine associated symptom of nausea!

 

FOODS THAT STOP NAUSEA IN ITS TRACKS.

Guest author: Kristen Seymour

Nausea: It’s one of those universal human experiences we can all commiserate with. In fact, it’s estimated that each year half of the adult population experiences at least one bout of nausea, which may or may not lead to vomiting. That makes sense because there are many reasons people feel nauseous.

 

WHAT TO EAT AND DRINK WHEN YOU FEEL NAUSEOUS

If you feel sick to your stomach, eating or drinking may be the last thing on your mind. And if your symptoms only last for a short time, abstaining could be the right thing to do.

However, if your symptoms persist for more than a couple of hours, not only is it important to stay hydrated (especially if you vomit or experience diarrhea) but there are some foods and drinks that can help quell your nausea, too. That said, if your symptoms persist for more than a day or are especially severe, you should contact your doctor.

 

WATER AND LIGHT OR CLEAR BEVERAGES

Even when you’re healthy, being dehydrated can leave you feeling pretty crummy. When you already feel awful, dehydration exacerbates the effect. And, if you have a fever and/or ­­struggle to keep food or drinks down, you could become dangerously dehydrated without realizing it. Water alone is a great start, but if you lose fluids through vomiting or diarrhea, you may want to incorporate sips of coconut water, clear juices, or sports drinks. Flat ginger ale can also be a good option, but be cautious with carbonation as this could upset your stomach further.

Beverages and foods that are cold may be more appealing (or less likely to turn your stomach) than warm ones because they’re typically less fragrant. Sip small amounts rather than guzzling a whole glass, and consider sucking on small ice chips or a popsicle.

 

GINGER

This ancient herb has historically been used to relieve stomach upset, and the evidence that it works isn’t only anecdotal, it’s been proven in a variety of modern scientific studies, too. Keep in mind that effectiveness is tied to the amount consumed: Most studies use ½ to 1½ grams (or the equivalent) of dried ginger daily. But many common methods of consuming ginger (ginger tea, ginger ale, candied ginger slices, ginger cookies) make it hard to measure how much you’re getting. Taking ginger capsules or using your own fresh or dried ginger for tea is probably the best way to track your intake. If you’re pregnant or breastfeeding, talk to your doctor before using ginger for nausea.

 

BROTH OR SIMPLE SOUPS

When you’re ready to venture beyond clear fluids, broth is a great next step because it provides hydration, electrolytes, and a little more flavor, which may help you ease into real food. Broth is also a versatile base you can add more nutrition to in the form of chicken (diced small), vegetables, noodles, or rice as your body becomes capable of handling heartier fare. Just be sure to keep the spices and seasonings to a minimum at first.

 

BLAND, DRY STARCHY FOODS

Bread, crackers, rice, noodles, and other similarly simple foods are sick-day staples, although interestingly, this is one nausea-fighting food group that lacks scientific research to back up its effectiveness. It’s believed that starchy foods may help absorb some of the stomach acid that contributes to feeling nauseated, and it’s well-documented that we’re more likely to experience nausea on an empty stomach than when we’ve eaten a little something. So if you’re up for it, try nibbling on a soda cracker or a little steamed rice. You can add a small amount of seasoning, such as salt (or ginger) if it sounds appetizing.

 

APPLESAUCE

Not only is applesauce a gentle, healthy source of carbs (which can help you build back your energy), but it can also benefit you if you’re experiencing diarrhea. That’s because it has high dietary pectin, which helps by binding substances in the intestine, adding bulk to loose stools. Applesauce is part of the BRAT diet (bananas, rice, applesauce, and toast), which has long been a go-to grocery list for people with nausea.

 

BANANAS

Many of the foods on this list can soothe your stomach but lack in overall nutritional value. Not so with bananas. This nutrient-dense fruit is not only soft and easy to eat, it also provides you with approximately 105 calories, 27 grams of carbs, and 12 percent of potassium and 22 percent of vitamin B6 needs for the day (for a medium banana). One tip: The riper the banana, the more fragrant, so if smells turn you off, try a greener one.

 

HERBAL TEA

We mentioned that cold drinks are often more appealing than hot, but sometimes sipping on something warm provides much-needed comfort. In that case, try a caffeine-free herbal tea. See if perhaps peppermint, chamomile, or ginger sounds like something you’d like to sip. You may find that lukewarm or iced works better for you than hot.

 

Each person—and each instance of nausea—is different, so if you’re under the weather, don’t force yourself to eat a particular food if the smell turns your stomach. Listen to your body and take it slow; you’ll be back to your regular meals before long.

 

The original article can also be seen here, as originally published on Health Perch – A Digital Health Magazine.

 

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 April 9th, 2021 at 12:47 am

RIMEGEPANT (NURTEC ODT) VS. ATOGEPANT FOR MIGRAINE PREVENTION. THE GEPANTS AREN’T JUST FOR ABORTIVE TREATMENT ANYMORE!

@Neuralgroover

BACKGROUND

The gepants were the first to emerge as new migraine abortive options, and the first new migraine specific abortive class since the triptans came to market in 1992. The first to become available was Ubrogepant (Ubrelvy) from Allergan in January 2020. Then Rimegepant (Nurtec ODT (orally dissolvable tablet)) became available by Biohaven shortly after in February 2020. The gepants have been game changers in the migraine abortive arena. However, they are now bringing their benefits to the migraine preventive realm, following a mind-blowing trifecta collision of the worlds of gepants, abortive and preventive therapy with Rimegepant (Nurtec ODT) and Atogepant!

 

I can hear you now. Rimegepant (Nurtec ODT) for migraine prevention? Atogepant for migraine prevention? Yes, you heard correctly. Are these available yet? We’ll discuss this and these new options a bit further down.

 

HOW DO THE GEPANTS WORK?

To review, during a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP causes inflammation around the brain and cerebral arteries (“sterile inflammation”) in the dural membrane surrounding the brain, intensified pain signals, enhanced transmission of pain signals through the trigeminal nerves into the brainstem and into the brain, and dilation of the cerebral arteries through the dural membrane, which in turn leads to further increasing pain signals via the trigeminal nerve endings covering the cerebral arteries. The result is intense migraine pain (as you are unfortunately very familiar with). So, if we can block these steps of migraine pain, the attack should be aborted quickly, and not as severe. That’s the thinking here, and that’s where the CGRP medications (gepants and CGRP monoclonal antibodies) come into play.

 

The gepants work as CGRP receptor antagonists, which means they directly target and block (antagonist) the CGRP receptor. This results in the medication “blocking” the CGRP inflammatory protein from sticking to the CGRP receptor to activate it, and thus prevents it from “turning on” these pathways of migraine pain. So, you get reversal of cerebral vasodilation, which decreases the firing off of the trigeminal nerves, and cessation of electrical pain signals. Notably, the gepants do this in a way that does not cause vasconstriction, in contrast to the triptans. Thus, they are felt to be safe in those with cardiovascular or cerebrovascular disease (as opposed to the triptans). By blocking the CGRP receptor, you also get reversal of the neurogenic inflammation going on through the brain and around the arteries, and you block the electrical transmission of migraine pain from traveling from the trigeminal nerves into the brainstem, and ultimately into the brain.

 

GEPANTS FOR MIGRAINE PREVENTION

Rimegepant (Nurtec ODT) and Ubrogepant (Ubrelvy) were created and FDA approved for the abortive (as needed) treatment of migraine in 2020. The goal of migraine abortive treatment 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. We want you to avoid having to go lay down and miss that family/social event, work meeting, or whatever else you had planned, and instead end up spending the whole day in a dark quiet bedroom. As opposed to conventional migraine abortives such as triptans, NSAIDs, and other analgesics, the gepants have the unique characteristic that they do not cause rebound headache (medication overuse headache), which is why they have also been evaluated as daily preventive medications as we’ll discuss below.

 

Abortive treatments are in contrast to migraine preventive treatments which are a continuous treatment (not just taken as needed). Preventive treatments include a daily pill, a monthly/quarterly treatment such as CGRP mAbs (Aimovig, Ajovy, Emgality, Vyepti), or neuromodulation devices. The goal of migraine preventive treatment is to lessen the frequency and/or severity of migraine attacks and are discussed in more detail here. 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.

 

Notably, for many decades, we have never had migraine specific preventive treatment. What I mean is that the treatments we have always used have been adopted from and limited to medications including antiseizure, antidepressant/anxiety, and blood pressure medications. Although many patients certainly do well with these preventive options, none of these medicines have been scientifically engineered and created specifically to target migraine pathophysiology for migraine prevention. That was until 2018 with the first once monthly self-injection CGRP monoclonal antibody (mAb) Erenumab (Aimovig) came to market, and was followed by 3 more CGRP mAbs; Fremanazumab (Ajovy), Galcanezumab (Emgality), and Eptinizumab (Vyepti).

 

The CGRP mAbs were a major step forward for migraine prevention. However, up to this point, we still have not had an oral pill that has been engineered and created purely and only for migraine prevention (not “adopted” from a different medicine class). That was until now. These new gepant medications will be the first in history to assume this new role.

 

As mentioned earlier, the worlds of the gepants, abortive and preventive treatments are all colliding. There are 2 gepants which have been submitted to the FDA for their pending approval as migraine preventives, and both seem very effective!! As of now, neither has officially received FDA approval for migraine prevention yet. Stay tuned to this blog for developments in FDA approval, further data and information.

 

These gepants are Rimegepant (Nurtec ODT, but unknown if the preventive name will be different) from Biohaven and Atogepant (brand name currently unknown) from Allergan/Abbvie. Notably, Rimegepant would be FDA approved as both an abortive and preventive medicine simultaneously, which would be a first ever. Yes, I know your mind has just been blown. Let’s discuss them and the currently available data, which can be found on each company’s website.

 

RIMEGEPANT

Rimegepant 75 mg every other day was studied in the preventive treatment of both episodic (4-14 days per month) and chronic migraine (15-30 days per month) during a 12-week double-blind randomized placebo-controlled treatment which included 747 patients. Patients were allowed to take 1 preventive migraine medication, (excluding CGRP receptor antagonists and CGRP monoclonal antibodies), as long as they were on a stable dose for at least 3 months and did not change it during the study. Patients were instructed to take 1 tablet every other day for preventive purposes during the study. They were allowed to use rescue medications including triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and other typical analgesics. Rimegepant was not permitted as a rescue medication during the 12-week double-blind treatment phase.

 

A 52-week open-label extension phase was also conducted in which patients dosed rimegepant 75 mg every other day and were allowed to take up to one dose of rimegepant 75 mg as needed on non-scheduled dosing days to treat migraine attacks. The data from this will be forthcoming.

 

The primary endpoint of this study measured the change from baseline in mean number of migraine days per month in weeks 9-12. Secondary endpoints included achievement of at least a 50% reduction in the mean number of moderate to severe migraine days per month during weeks 9-12, change in the mean number of migraine days per month across the full treatment phase (Weeks 1-12), mean number of rescue medication days per month during weeks 9-12, and change in the mean number of migraine days per month in the first 4 weeks (Weeks 1-4). The study met its primary endpoint, demonstrating a statistically significant reduction from baseline in monthly migraine days in patients treated with rimegepant compared with placebo. Patients receiving rimegepant 75 mg every other day (N=348) experienced a statistically significant reduction of 4.3 monthly migraine days for Rimegepant compared to a 3.5 day reduction in the placebo group (N=347).

 

Rimegepant was more effective than placebo regarding the percent of participants with at least a 50% reduction in the mean number of moderate to severe migraine days per month during weeks 9-12. Rimegepant was also superior to placebo for the mean change in mean number of total migraine days per month over the 3-month treatment period. The rimegepant and placebo treatment groups were not statistically different with respect to the mean days of rescue medication per month during weeks 9-12.

 

The safety and tolerability of rimegepant across the 12-week double-blind treatment phase was similar to that of placebo. Adverse events (AEs) occurring in greater than 2% of participants in the rimegepant treated group were nasopharyngitis, nausea, urinary tract infection, and upper respiratory tract infection. Nearly all AEs were mild or moderate in intensity. No treatment-related serious AEs were reported in the rimegepant group. Discontinuations due to an AE were low in both groups (rimegepant 2% and placebo 1%). Four (1%) participants who were treated with rimegepant and 2 (1%) participants who were treated with placebo experienced transaminase (ALT or AST) elevations greater than 3x upper limit of normal (ULN). One participant in the rimegepant group had asymptomatic elevation of transaminases with ALT greater than 10x ULN; alkaline phosphatase and bilirubin levels remained within normal limits. One participant in the rimegepant group had bilirubin levels greater than 2x ULN and was diagnosed with Gilbert’s syndrome after genomic testing.

 

ATOGEPANT

Atogepant 10 mg, 30 mg and 60 mg doses once daily were studied in the preventive treatment of episodic migraine (4-14 days per month) during a 12-week double-blind randomized placebo-controlled treatment which included 910 patients. Atogepant met the primary endpoint of statistically significant reduction from baseline in mean monthly migraine days, compared to placebo, for all doses evaluated across the 12-week treatment period. Patients treated in the 10 mg/30 mg/60 mg atogepant arms experienced a decrease of 3.69/3.86/4.2 days per month, respectively, all compared to patients in the placebo arm, who experienced a decrease of 2.48 days.

 

Atogepant also showed statistically significant improvements in six secondary endpoints in the 30 mg and 60 mg once-daily treatment arms. A key secondary endpoint measured the proportion of patients that achieved at least a 50% reduction in mean monthly migraine days across the 12-week treatment period. Results showed that 55.6%/58.7%/60.8% of patients in the 10 mg/30 mg/60 mg atogepant arms, respectively, achieved at least a 50% reduction, compared to 29.0% of patients in the placebo arm. Additional secondary endpoints measured across the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute-medication use days, and mean monthly performance of daily activities and physical impairment domain scores. The 30 mg and 60 mg doses resulted in statistically significant improvements in all secondary endpoints, while treatment with the 10 mg dose resulted in statistically significant improvements in four out of the six secondary endpoints.

 

No significant safety risks were observed. Serious adverse events occurred in 0.9% of patients treated in the atogepant 10 mg arm compared to 0.9% of patients in the placebo arm (so basically, no difference). No patients in the atogepant 30 mg or 60 mg treatment arms experienced a serious adverse event. The most common adverse events reported with a frequency ≥ 5% in at least one atogepant treatment arm, and greater than placebo, were constipation (6.9-7.7% across all doses vs. 0.5% for placebo), nausea (4.4-6.1% across all doses vs. 1.8% for placebo), and upper respiratory tract infection (3.9-5.7% across all doses vs. 4.5% for placebo). The majority of cases of constipation, nausea and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.

 

Stay tuned! As more information, data, and official FDA approval is granted for each medication, this blog will continue to be updated…

 

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 April 10th, 2021 at 05:23 am

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

@Neuralgroover

Background

Let’s talk about Botox for migraines. 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.

 

Can I get Botox with the Covid-19 vaccine?

The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and Botox injections, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving Botox were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that Botox can not be used along with receiving Covid-19 vaccination, nor does it need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving both because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it.  However, Botox does not have any significant influence on the immune system (it does not cause immunosuppression, etc). Rarely, the immune system of some patients can form neutralizing antibodies against Botox, and this can weaken Botox’s effectiveness in decreasing migraine frequency and severity. However, this issue really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of Botox, nor will Botox lessen the effectiveness of the Covid-19 vaccine. The topic of Covid-19 headache, Covid-19 vaccination, and the use of Botox or CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) is discussed further here.

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines.

 

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 April 9th, 2021 at 12:46 am

CORONAVIRUS (COVID-19) HEADACHE, COVID-19 HEADACHE 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. Headache from the Covid-19 vaccine is also being reported for high proportion of patients, and this is also discussed further down.

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.

In addition to stress, quarantining and working from home have introduced many other variables into day to day life which are common migraine triggers such as changes in eating habits, changes in sleep patterns, types of foods and snacks eaten (which means consumption of more migraine triggering food additives, sugars, etc.), and for some, weight gain (by the way, obesity is associated with a 5x increased risk of chronic migraine (15-30 days of headache with 8 or more days being migrainous).

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), Botox, 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. Tension type headache is also discussed further here. 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.

 

HEADACHES FROM COVID-19 VACCINE

Now that the Covid-19 vaccine is available, Covid-19 vaccine side effects are reported in some patients, including headaches. The Covid-19 vaccine headaches have ranged from mild and a temporary side effect to more severe and extended. So further observation will be useful. Some early data has reported that headaches occur in 35.4% of patients receiving the first Moderna Covid-19 vaccine injection, and 62.8% of patients after receiving the second injection. For the Pfizer Covid-19 vaccine, 41% of patients reported headaches after the first injection, and 51.7% of patients got a headache after the second injection. 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.

 

CAN I STILL GET BOTOX WITH THE COVID-19 VACCINE?

CAN I STILL USE MY CGRP MONOCLONAL ANTIBODY TREATMENT (AIMOVIG, AJOVY, EMGALITY, VYEPTI) WITH THE COVID-19 VACCINE?

The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs or Botox injections, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving Botox or CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments can not be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. However, neither Botox nor the CGRP mAbs have any significant influence on the immune system (they do not cause immunosuppression, etc.). Rarely, the immune system of some patients can form neutralizing antibodies against Botox and the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines.

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 April 9th, 2021 at 12:50 am

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 still use my CGRP monoclonal antibody treatment (Aimovig, Ajovy, Emgality, Vyepti) with the Covid-19 vaccine? 

The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and CGRP mAbs, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that these treatments can not be used along with receiving Covid-19 vaccination, nor do they need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving either of these treatments in relation to Covid-19 vaccination because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it. The CGRP mAbs do not have any significant influence on the immune system (they do not cause immunosuppression, etc.). Rarely, the immune system of some patients can form neutralizing antibodies against the CGRP mAbs, and this can weaken the effectiveness of these treatments in their ability to decrease migraine frequency and severity. However, this rarity really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of these treatments, nor will these treatments lessen the effectiveness of the Covid-19 vaccine.

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination, but not with Botox or the CGRP mAbs. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines. The topic of Covid-19 headache, Covid-19 vaccination, and the use of Botox is discussed further here.

 

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.

There is an Aimovig coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per month, with the first 3 doses free.

 

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.

There is an Ajovy coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per month.

 

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.

There is an Emgality coupon available on the company’s website in which most commercial insurance plans can get the medication for $0 per month for up to 12 months.

 

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.

There is a Vyepti coupon available on the company’s website in which most commercial insurance plans can get the medication for $5 per infusion every 3 months.

 

Data comparisons of the CGRP mAbs

The comprehensive table which follows compares all available data between the 4 CGRP mAbs, as I lityhave 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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