Posts Tagged "migraine treatment"

Last updated on April 30th, 2021 at 11:13 pm

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!

 

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Last updated on October 4th, 2021 at 01:52 pm

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

@Neuralgroover

BACKGROUND

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

 

First off, these medications are all migraine specific abortive/acute (as needed) options. 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. This is in contrast to migraine preventive treatments which are a continuous treatment. Preventive treatments include a daily pill, a monthly/quarterly treatment such as CGRP monoclonal antibodies (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 these options 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.

 

Since the development and availability of sumatriptan in 1992, the primary migraine specific abortive/acute (as needed) option available has been the triptans. Triptans (Imitrex, Maxalt, etc.) work great for a lot of people. However, about 30% of patients do not respond to triptans. Others cannot tolerate side effects, or they cannot use them because of medical contraindications (such as coronary artery disease, peripheral artery disease, cerebrovascular disease, stroke, etc.). Triptans are also contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction). They have been historically contraindicated in hemiplegic migraine or basilar migraine (now called migraine with brainstem aura) due to theoretical concerns of vasoconstriction potentially causing stroke. When the triptan studies were done previously, they excluded patients with these forms of migraine due to the ongoing vascular theory of migraine at that time. The vascular theory of migraine assumed that vasoconstriction and lack of blood flow was the cause of aura and neurologic features with migraine. So the thinking was that if you cause further vasoconstriction with a triptan, you may cause stroke. However, we now know that these phenomenon are primarily of an electrical basis and not a vascular basis. Therefore many specialists have gotten more liberal with the use of triptans in patients with hemiplegic or basilar migraine, and there have been a number of case series and case reports of these patients using triptans without any problems.

 

The alternatives to triptans have historically been the ergots (ergotamine, DHE) which can be complicated to use, tend to have an excess of side effects for many, and have the same medical contraindications as triptans. NSAIDs and over the counter analgesics are also commonly used, although many do not respond to or cannot take them due to other medical conditions. Even worse are opiates/opioids and butalbital medications such as fioricet, both of which (as do excess triptans, NSAIDS, OTCs) have a high risk of leading to medication overuse headache (rebound headache), as discussed here.  For close to 3 decades, these have remained the only limited options of acute/abortive migraine treatment, despite migraine being such a widespread common disorder! More recently, neuromodulation devices have also become available as abortive options.

 

Thankfully, these limited options have now expanded to 3 new migraine abortive options in adults between 2 new classes which became available commercially in 2020; the gepants and the ditans. These medications can be used SAFELY in all of the medical contraindications mentioned above! These 3 new abortive medications are compared and contrasted with one another, as well as with the triptans in the table which I constructed below.

 

GEPANTS

The gepants were the first to emerge as new migraine abortive options, first with Ubrogepant (Ubrelvy) which became available from Allergan in January 2020 and then Rimegepant (Nurtec ODT (orally dissolvable tablet)) became available by Biohaven in February 2020.

 

During a migraine attack, the trigeminal nerves release a variety of inflammatory proteins. One of the main proteins is called CGRP (calcitonin gene related peptide). CGRP causes 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.

 

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

 

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

 

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

 

Given that Ubrelvy and Nurtec ODT are of the same gepant class, they each have their own marketing pitch to differentiate them, although the bottom line is that they are both excellent options. Although they are both very effective for most patients, I commonly see patients who may respond to one better than the other. So if one of them does not help, it is worth trying the other one as well.

 

Ubrelvy (Ubrogepant)

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

 

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

 

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

 

Nurtec ODT (Rimegepant)

Biohaven boasts that Nurtec ODT 75 mg dissolves under or on the tongue in seconds, and starts working in minutes (15 minutes in some patients). They highlight that it does not require water or other liquids to take with the dose, so it can be taken anytime and anywhere. It is taken as a simple single strength single dose. They also point out that pain relief and pain freedom lasts up to 48 hours for many patients, which makes sense because it has the longest half-life (11 hours). The clinical data highlights of Nurtec ODT are that at 15 minutes, you get separation from placebo of both pain relief and return to normal function (but not yet statistically superior). At 1 hour, pain relief and return to normal function become statistically superior to placebo. At 1.5 hours, you get additional statistical superiority over placebo of pain freedom and freedom from most bothersome migraine symptom (nausea, photophobia or phonophobia). For the vast majority of patients, the superiority of all of these trial endpoints over placebo remain sustained through 48 hours.

 

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

 

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

 

Notably, on 5/27/21, Nurtec ODT made history as the first and only FDA approved medication for BOTH abortive and preventive migraine treatment simultaneously, and the only option with this flexibility! Nurtec ODT as a preventive migraine treatment is discussed further here. This move followed clinical trials showing that patients taking 75 mg of Rimegepant every other day experienced a 4.3 day reduction from baseline in monthly migraine days, a 30% drop of migraines within even the first week, and 49% of patients had a greater than 50% reduction in monthly migraine days.

 

Notably, on 9/28/21, Qulipta (Atogepant) became the second oral CGRP preventive gepant medication to become FDA approved for migraine prevention (not dually approved for both abortive and preventive). It is taken once daily. So, Nurtec ODT and Qulipta have become the first oral CGRP preventive medication options. They are both of the gepant medication family, which is different than the CGRP mAb family, but none the less now offer an oral alternative to once monthly CGRP monoclonal antibody injections.

 

Can I use a CGRP monoclonal antibody (mAb) (Aimovig, Ajovy, Emgality, Vyepti) with Botox injections?

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.

 

Can I use a CGRP mAb (Aimovig, Ajovy, Emgality, Vyepti) with the gepants (Nurtec, Ubrelvy)?

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 they had added erenumab (Aimovig) once monthly injection as a preventive treatment. After Aimovig was added, patient 1 had 100% relief for 7 of 7 acute migraine attacks treated with Nurtec. Patient 2 had 100% relief for 9 of 9 acute migraine attacks treated with Nurtec. So, the combination of using Nurtec abortively in addition to using Aimovig preventively appeared to provide an even more effective acute migraine response. Theoretically, it would make sense that benefit would be greater with both classes of medicines combined because they are entirely different types of medications targeting aspects of the same migraine pathway simultaneously (either targeting the CGRP receptor or the CGRP ligand protein). Larger studies to confirm the suspicion that they likely work together synergistically will be helpful.

 

There was a larger safety study publication which evaluated the acute treatment of migraine with Rimegepant while using a CGRP monoclonal antibody for the prevention of migraine. The CGRP mAbs used were Erenumab (Aimovig) (7 patients), Fremanezumab (Ajovy) (4 patients), and Galcanezumab (Emgality) (2 patients). The study determined that Rimegepant used as an acute migraine treatment in combination with CGRP mAbs for migraine prevention was well tolerated with no safety issues identified. The researchers concluded that the probability between these 2 classes (gepants and CGRP mAbs) was low, especially because they have entirely different pathways of drug metabolism. They also concluded that existing evidence supports the safety of combined use, although further larger research was warranted.

 

DITANS

Reyvow (Lasmiditan)

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

 

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

 

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

 

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

 

SUMMARY

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

 

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

 

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

60 minutes with 50 mg dose

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

31% (placebo)

43% (50 mg)

N/A (100 mg)

36.7% (placebo)

37.3% (50 mg)

»41% (100 mg)

»46% (200 mg)

30.6% (placebo)

20-35% (100 mg)

12-21% (placebo)

Differences in pain relief at 15 minutes 8%

5% (placebo)

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

17% (placebo)

19% (50 mg)

N/A (100 mg)

20% (placebo)

»15% (50 mg)

17.5% (100 mg)

19.1% (200 mg)

13.4% (placebo)

11% (100 mg)

12% (placebo)

2 hour pain relief 59%

43% (placebo)

61.7% (50 mg)

61.4% (100 mg)

48.7% (placebo)

59% (50 mg)

59.4-64.8% (100 mg)

59.5-65% (200 mg)

42.2-47.7% (placebo)

46-67% (100 mg)

18-44% (placebo)

2 hour pain freedom 21%

11% (placebo)

20.5% (50 mg)

21.2% (100 mg)

13% (placebo)

28% (50 mg)

28-31% (100 mg)

32-39% (200 mg)

15-21% (placebo)

22-33% (100 mg)

3-13% (placebo)

8 hour pain freedom with 1 dose 56%

33% (placebo)

82.3% (50 mg)

82.7% (100 mg)

69.8% (placebo)

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

56% (placebo)

92% (50 mg)

N/A (100 mg)

82% (placebo)

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

33.3% (50 mg/placebo)

51.6% (100 mg/100 mg)

33.3% (100 mg/placebo)

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

5.6% (placebo)

13.6% (50 mg)

15.4% (100 mg)

8.4% (placebo)

17.2% (50 mg)

14.8-17.9% (100 mg)

18.6-22.7% (200 mg)

7.6-13.4% (placebo)

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

27.7% (placebo)

31.5% (50 mg)

34% (100 mg)

17.5% (placebo)

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

27% (placebo)

38.7% (50 mg)

37.7% (100 mg)

27.6% (placebo)

41% (50 mg)

41-44% (100 mg)

41-49% (200 mg)

30-33% (placebo)

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

92.4% (100 mg)

77.7% (placebo)

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

2%

0.4% (placebo)

Nausea

2% (50 mg)

4% (100 mg)

2% (placebo)

 

Somnolence/Sedation

2% (50 mg)

3% (100 mg)

1% (placebo)

Nausea

3% (50 mg)

4% (100 mg)

4% (200 mg)

2% (placebo)

 

Somnolence/Sedation

6% (50 mg)

6% (100 mg)

7% (200 mg)

2% (placebo)

 

Dizziness

9% (50 mg)

15% (100 mg)

17% (200 mg)

3% (placebo)

 

Paresthesias

3% (50 mg)

7% (100 mg)

9% (200 mg)

2% (placebo)

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

 

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

FIRST, LET’S DECIDE WHERE TO START:

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

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR 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.

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Last updated on September 17th, 2021 at 06:37 am

 

REBOUND HEADACHE (MEDICATION OVERUSE HEADACHE); WHAT IT IS, AND HOW TO BREAK FREE FROM THE VICIOUS CYCLE – 2021.

@Neuralgroover

 

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

 

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

 

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

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

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

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

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

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

 

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

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

 

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

 

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

FIRST, LET’S DECIDE WHERE TO START:

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

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR 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.

Read More

Last updated on September 17th, 2021 at 06:36 am

WHAT ARE THE TRIPTAN DIFFERENCES AND WHICH IS BEST? HOW TO FINE-TUNE WHICH TRIPTAN MAY BE MOST EFFECTIVE FOR YOU.

@Neuralgroover

BACKGROUND:

Imitrex vs. Maxalt, Zomig vs. Maxalt, Amerge vs. Relpax, Frova vs. Imitrex, Maxalt vs. Relpax, Zomig vs. Imitrex, Frova vs. Amerge, Imitrex vs. Treximet. Maxalt vs. Frova. Axert vs. Imitrex. These are the triptans for migraine. There are 8 triptan types within the triptans medication class and include Imitrex (Sumatriptan) vs. Maxalt (Rizatriptan) vs. Relpax (Eletriptan) vs. Zomig (Zolmitriptan) vs. Frova (Frovatriptan) vs. Amerge (Naratriptan) vs. Axert (Almotriptan) vs. Treximet (Sumatriptan/Naproxen).

 

So what are the best triptans to use? Well let’s back up a little first. The ergot based medications such as DHE (dihydroergotamine) and cafergot (ergotamine + caffeine) have been the oldest migraine abortive medications used, which are still used today. However, they often have many side effects for patients and eventually the migraine specific triptans were developed for aborting migraine. Since 1992 (when Sumatriptan first became available), the triptans have been the first and only migraine specific abortive medications available up until 2020 when two new classes of migraine specific abortive medications have FINALLY become available with the gepants (Ubrelvy, Nurtec) and ditans (Reyvow). These new migraine abortive medications can be read about in more detail here.

 

The first triptan developed was sumatriptan in 1991 and since that time there have been a total of 8 triptan options to choose from. So how do the triptans work? They work by activating (agonist) the serotonin sub-receptor 5-HT1B. The result of activating this receptor is that it helps to constrict (narrow) the dilated inflamed pain-producing meningeal blood vessels which occurs during a migraine attack. The 5-HT1B receptors are also present in the brainstem, and likely play a role in modulating the electrical event of a migraine. Triptans also work by activating (agonist) the serotonin sub-receptor 5-HT1D. The result of activating this receptor is that they stop the trigeminal nerves from releasing a variety of inflammatory proteins around the brain and blood vessels which normally leads to pain during a migraine attack. This also interferes with normal pain processing between the brainstem and the brain (helps to block this electrical transmission), and it helps to block the nausea and vomiting centers in the brainstem. Triptans help to normalize levels of and decrease the release of a very inflammatory protein released during a migraine called CGRP (calcitonin gene related protein). Triptans also inhibit mast cell degranulation in the dural membranes, which also lessens the sterile inflammation which occurs during a migraine.

 

WHAT ARE THE SIDE EFFECTS OF TRIPTANS?

Most patients tolerate triptans very well, however, many patients have side effects and discontinue them. So let’s discuss triptans side effects. Just like any medicine, some patients may have more side effects than others. Furthermore, about 30% of patients with migraine may not respond to triptans (triptan non-responder). If side effects do occur, there is some variability between the different types of triptans. Potential side effects of the triptans include palpitations or racing heart beat, nausea, tingling, numbness or flushing in the face or extremities, drowsiness, fatigue, dizziness, and tightness or pressure in the chest, neck, or jaw. Although the chest pressure is not common, it is usually of a muscular and not a non-cardiac (heart) cause, so it can be scary if you don’t know about this potential side effect. With that said, chest pain could still potentially be a sign of heart attack (myocardial infarction) in patients with vascular risk factors and unknown coronary disease because the triptans do cause some slight vasoconstriction (narrowing) of arteries. So if there is already narrowing in an artery, increasing further narrowing could lead to lack of blood flow to the heart with subsequent heart attack in those at risk.

 

WHEN SHOULD TRIPTANS NOT BE USED?

Triptans can cause a mild degree of artery constriction (narrowing) due to its activity at the 5-HT1B receptor as discussed above. This could theoretically occur in narrowed arteries from cholesterol build up, such as in the heart. Therefore, triptans should not be used in patients who have coronary artery disease, cerebrovascular disease (stroke), peripheral arterial disease, or uncontrolled risk factors for these diseases (high blood pressure, cholesterol, diabetes, smoking, family history of early heart disease) because chest pain for them could truly represent heart attack. If there is concern for the possibility of underlying cardiovascular disease, a cardiac stress test should be performed prior to triptan prescription.

 

Triptans are also considered to be contraindicated in patients with visual snow, persistent migraine aura, and migrainous stroke (infarction) due to theoretical concerns of vasoconstriction potentially causing stroke. This contraindication has historically also included hemiplegic migraine and basilar migraine (now called migraine with brainstem aura). When the triptan studies were done previously, they excluded patients with these forms of migraine due to the ongoing vascular theory of migraine at that time. The vascular theory of migraine assumed that vasoconstriction and lack of blood flow was the cause of aura and neurologic features with migraine. So the thinking was that if you cause further vasoconstriction with a triptan, you may cause stroke. However, we now know that these phenomenon are primarily of an electrical basis and not a vascular basis. Therefore many specialists have gotten more liberal with the use of triptans in patients with hemiplegic or basilar migraine, and there have been a number of case series and case reports of these patients using triptans without any problems. However, larger confirmatory studies would be preferable.

 

Patients that can not use triptans due to side effects, or if they have any of these medical contraindications noted above, should consider one of the newer types of migraine abortive medications available with either the gepants (Ubrelvy, Nurtec), ditans (Reyvow) or neuromodulatory devices. Ubrelvy, Nurtec, and Reyvow are not triptans. These newer options often have a much lower side effect profile, can be taken in the setting of these medical contraindications to triptans mentioned above, and work by an entirely different mechanism of action.

 

It is also important to know that triptans can cause medication overuse headache (rebound headache) if used consistently greater than 10 days per month on average. The result is that the headache continues to worsen in frequency and/or severity. This also happens with NSAIDs, over the counter pain meds, and other types of as-needed pain medications. The phenomenon of rebound headache is discussed in much greater detail here. Notably, the gepants (Ubrelvy, Nurtec) do not cause rebound headache. If triptans, or any migraine abortive medication, is having to be used at this high frequency, a preventive migraine treatment should be used until the migraine and headache frequency is significantly improved consistently for several months. 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.

 

WHAT IS THE BEST TRIPTAN TO USE?

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

 

LIST OF TRIPTANS:

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

GROUP 1 TRIPTANS:

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

 

GROUP 2 TRIPTANS:

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

 

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

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

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

 

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

 

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

 

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

 

TRIPTAN PEARLS IN FURTHER FINE-TUNING TRIPTAN CHOICES:

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

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

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

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

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

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

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

 

CONCLUSIONS:

The triptans were and have been a game changer for millions of migraine patients in aborting migraine attacks. Using the highest available triptan dose is also generally recommended to see the full effect. We see many patients who have “failed triptans”, but on further history they were put on very low doses (such as 25 mg sumatriptan, when 100 mg is the standard dose). Even so, about 30% of migraineurs do not respond to triptans, only 1/3rd are pain-free at 2 hours, and only 17-25% remain pain-free at 24 hours. Therefore, although the majority respond well to triptans, not everyone does. Luckily, there are other medication options including two brand new classes of migraine abortive medications (gepants, ditans), and these are detailed here.

 

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

FIRST, LET’S DECIDE WHERE TO START:

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

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR 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.

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Last updated on September 17th, 2021 at 06:36 am

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

@Neuralgroover

 

 

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

 

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

 

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

 

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

 

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

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

 

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

 

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

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

 

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

 

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

 

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

 

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

 

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

FIRST, LET’S DECIDE WHERE TO START:

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

 

IF YOU DON’T HAVE AN EXISTING HEADACHE, MIGRAINE, OR FACIAL PAIN DIAGNOSIS AND ARE LOOKING FOR 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.

Read More