Does GammaCore Treat Migraine?
Does GammaCore Treat Migraine?
General statement. Migraine is a genetic condition that is inherited through your DNA. The genes that transmit migraine have been found and published in the medical literature. Migraine occurs in 25 % of women and 6 % of men. For women migraine is their most common chronic medical problem and more prevalent than diabetes, heart disease, or arthritis. Migraine is the fifth most common cause of disability worldwide in men and women and causes a large amount of clinical and economic burden.
Migraine causes more than a million ER visits every year. An attack of migraine according to the International Classification of Headache Disorders 3 lasts 4-72 hours and is called episodic migraine if it occurs less than 14 days per month, or chronic migraine if there are more than 15 headache days a month, 8 of which have migraine features.
Although many medications are used for treatment of migraine, including the triptans, which are the best and most successful drugs, an estimated 3 million patients are dissatisfied with the current available treatment options.
Does GammaCore Treat Migraine? Yes, the FDA has approved GammaCore nVNS (vagus nerve stimulator) for acute treatment of migraine headache, saying it was “safe and effective.” Some adults felt relief as quickly as 30 minutes. Almost half of patients had little to almost no pain within 2 hours. GammaCore (nVNS) provided relief for more than 50% of attacks for many migraine patients. The majority of patients who were pain-free at 2 hours remained pain-free for 48 hours. GammaCore is effective for patients who have failed traditional oral or injectable medications such as triptans. GammaCore treatment for migraine avoids medication side effects.
1. What are the side effects of using GammaCore?
GammaCore treated patients did not have any serious treatment related side effects. Most of the reported side effects were mild, only occurring during the use of the device, and went away after each treatment. The most common side effects were discomfort and redness at the application site, dizziness, and a tingling feeling where the device was applied in the neck.
GammaCore has been shown to be safe and effective across a range of migraine populations in both the United States and Europe. Different treatment strategies have been evaluated showing good clinical, safety, and quality of life outcomes at various treatment study times.
2. How does GammaCore (nVNS) work?
GammaCore is a vagus nerve stimulator. The vagus nerve is one of the largest nerves in the parasympathetic division of the autonomic nervous system. GammaCore activates the vagus nerve by mild electrical stimulation. GammaCore therapy is not indicated for children; pregnant women; or patients with active implantable medical devices.
It is also not indicated for patients with carotid atherosclerosis, hypertension, bradycardia/tachycardia, or those with a metallic device. It shouldn’t be used in patients with a stent, bone plate, or bone screw near the neck. It also shouldn't be used at the same time as the use of a mobile phone or other portable electronic device.
3. What is the function of the vagus nerve?
The vagus nerve connects the medulla of the brain stem with various target organs in the body. One of the most well know functions of the vagus nerve is to cause the cells in the lining of the stomach to secrete acid to aid digestion. The vagus nerve helps regulate pain. The vagus nerve shuts off inflammation in the body and migraine is an inflammatory medical condition. Vagus nerve stimulators are also used to treat depression and epilepsy.
The vagus nerve has the longest course of all the cranial nerves, extending from the medulla to the abdomen. Its name is derived from the Latin “vagary” which means “wandering.” The vagus nerve originates from the medulla of the brainstem to neurons in the stomach, the upper and lower bowel, the bladder, and all the sexual organs.
4. History of migraine treatment through the years. Ancient humans, thinking opening the skull would release evil humors, used to perform trepanation and leave the skull open. Others used the disgusting treatment of putting warm goat dung on a headache patient’s head. Egyptian doctors placed a clay crocodile with grain in its mouth to the patient’s head held with a linen strip on which were written the names of gods as treatment.
Hippocrates in 400 BC described “sick headache” which is now thought to be a common feature of migraine and occurs in 20-50% of patients. Galen was a Roman physician in the 2nd century who described “hemicrania” which means half of head. Through the years the “he” was taken off and we are left with the word “micrania” which later became “migraine.”
One sided headache pain is found in 80% of migraine patients and is the most common feature of migraine.
William Shakespeare (1564–1616) in Othello had Desdemona tie up her husband’s head with a handkerchief, probably a common treatment in England in the middle ages, and also used currently for headache relief.
Desdomona: Why do you speak so faintly? Are you not well?
Othello: I have a pain upon my forehead here.
Desdomona: Let me but bind it hard, within this hour--It will be well.
Shakespeare used a similar treatment in King John. ”When your head did but ache, I knit my handkerchief about your brows.”
5. Ergotamine treatment.
Midwives in the 16th century started using ergotamine, made from a common fungus, as treatment for labor. Ergotamine causes strong vasoconstriction of arteries and the smooth muscle in the uterus, helping it to contract. Sandoz, the giant pharmacy company, started making injectable ergotamine for migraine in the early 19th century, since during migraine the arteries dilate and ergotamine is a vasoconstrictor. Then another ergot congener, DHE, dihydroergotamine, was discovered by Dr. Baynard Horton at the Mayo Clinic to be effective for migraine and DHE got FDA approval as an intramuscular injection for migraine in 1946.
All kinds of painkillers—oral and injectable have been used for treatment of migraine, from opioid narcotics to butalbital, from caffeine in Coca Cola and Dr. Pepper, Excedrin migraine, and BC powders, from Aspirin to Tylenol to Aleve to Advil, to Toradol injection in the rear end at the emergency room for a severe, long lasting migraine.
All these drugs have been used and the problem using them has been a poorly understood one, hidden underneath normal human experience, sort of like thinking that life of earth didn’t evolve or rocket in from outer space on an asteroid, but was made by the glory of God.
The problem is that all the painkillers mentioned if taken too often, can cause daily headache which used to be called “rebound headache” in the 1980 first edition of the International Classification of Headache Disorders, to now what should be termed as “medication overuse headache” in the 2018 edition of ICHD 3.
The limit now for all pain killers is no more often than 2 days a week and nobody should use opioids or butalbital drugs for headache unless they have coronary disease, out of reach hypertension, or they are a triptan failure.
Starting in 1991 Glaxo brought out the first triptan as 6mg subcutaneous, SC, Imitrex, now known as the generic, sumatriptan. Triptans hit the ground running and then travelled around the world and off into outer space because they were so successful. Glaxo made trillions of dollars as the first drug that blocked the release of the inflammatory chemicals that were released during a migraine was produced.
7. Types of triptans.
There are now 7 triptans, 5 for acute migraine-sumatriptan, eletriptan, rizatriptan, zomatriptan, and almotriptan, and 2 longer lasting drugs with special niche treatment for menstrual migraine-naratriptan and frovatriptan. Triptans are available for persons 12 years old and older.
8. Triptan effectiveness.
What is published regarding triptan effectiveness is that 80% of patients who treat at onset with a triptan are headache free in 2 hours. No other acute therapy drug for migraine comes close to this. A question regarding the triptans has always been, since there are 7 of them, which is the best.
9. Triptan contraindications.
The FDA has contraindications for using triptans, (which means, there is risk for using the drug. You probably shouldn’t take it.) General triptan rules—don’t use with a personal or strong family history of coronary artery disease. Don’t use with uncontrolled hypertension. Limit the dose in children, the elderly (defined here as over 65 years old.), and patients with basilar artery or complicated migraine (aura symptoms over 40 minutes.) Don’t mix the triptans or take with ergotamine within 24 hours.
10. Common triptan side effects
Side-effects are chest tightness or pressure, near fainting, neck/back pain which may be burning, a warm or hot feeling, dizziness, or drowsiness. The most common side effects in randomized, controlled trials of triptans included feelings of tingling, numbness, warmth, and pressure or tightness in the chest and neck. These effects, frequently referred to as triptan symptoms or triptan sensations, occur more often in women and younger people. The most alarming symptoms are the tightness and heaviness of the chest, neck, or throat, which mimic ischemic myocardial dysfunction. However, patients with these symptoms show no evidence of decreased myocardial perfusion on ECG; therefore, chest and throat symptoms are not thought to be of cardiac origin.
Triptan symptoms may be reduced by switching to a different triptan or reducing the dose. Patients receiving SC sumatriptan are more likely to experience side effects versus those taking oral formulations. In most cases, side effects were brief and mild-to-moderate, resulting in no change of therapy.
11. Triptans and SSRIs/SNRIs
The FDA has erroneously reported that there is a rare risk of development of serotonin syndrome in patients who take these drugs. Triptans block 5HD1D receptors to work for migraine and the FDA indicated a different numbered receptor than the one triptans block. This was discovered and written about by Dr. Randy Evans, a neurologist in Houston, Texas.
The FDA states the risk is estimated to be less than 0.03% of patients and life-threatening events are less than 0.002%. In a recent review of migraine experts none of them recommended that triptans and SSRIs or SNRIs be discontinued unless symptoms arise.
The symptoms of serotonin syndrome are restlessness, hallucination, loss of coordination, tachycardia, changes in blood pressure, fever, nausea, vomiting, or diarrhea. This risk is not real and is factitious with the use of triptans, but the FDA have not changed their advice.
Although cardiac ischemia in association with triptan use is rare, triptans are contraindicated in patients with coronary artery disease (CAD), cerebrovascular disease, peripheral vascular disease, and uncontrolled hypertension. The coronary artery vessels have an abundance of 5-HT1B/1D receptors, which is significant because about 20% to 30% of the constrictor response is mediated through 5-HT1, whereas the 5HT2 receptors are the main receptors responsible for vasoconstriction. Newer second-generation triptans are more selective than sumatriptan in their action on the cerebral vessel, thereby decreasing cardiac risks, but all drugs in this class are contraindicated in patients with coronary disease.13
12. Which triptan is the best? The problem is that no pharmaceutical company ever dared to do a side by side comparison, like comparing oral sumatriptan with rizatriptan. Such a study would cost millions of dollars, take several years, and then be submitted to the FDA. Somebody would win and somebody would lose.
My personal involvement with this issue of the effectiveness of the various triptans has to do with the fact that I have written 2 textbooks on migraine, one a big 400 page 800 reference migraine book and the other a small 40 page book, on Migraine, the first in the Mini Neurology Series. I need to know the best drug to write it in my books and on my webpage to accurately e0ducate readers.
13. Injectable subcutaneous sumatriptan 6 mg. wins the prize. The denouement came 4 years ago when the American Academy of Neurology headache section said that injectable sc sumatriptan was the best drug of all the triptans. This was what I thought, but I needed someone with authority to say it. They published information that I have for sumatriptan alone, but not for any of the other triptans.
Consider that injectable or what is called parenteral delivered medications are the fastest, always better than oral or rectal, but similar to nasal spray delivery. Nasal sprays are fast, but deliver low dose medication in the body. Only sumatriptan has injectable SC delivery. Sumatriptan also comes as a nasal spray and 3 oral tablets-25, 50, and 100 mg.
The American Academy of Neurology reported that SC sumatriptan 6 mg onset was 10 minutes and the dose produced in the brain was 100 mg. The 25 mg nasal spray dose worked in 10 minutes, but gave a level of only 10 mg in the brain. The oral 100 mg tablet of sumatriptan dose, which is the most popular treatment for migraine, works in 30 minutes and gives a level in the brain of 30 mg. So, injectable 6 mg sumatriptan is 3 times faster and gives a dose that is 3 times bigger than oral 100 mg sumatriptan.
14. Electrical treatment. This discussion of previous treatment options for migraine leads into a new electrical stimulator, drug free method of treating migraine—the GammaCore, nVNS, vagus nerve stimulator.
GammaCore, produces a proprietary low-voltage electrical signal comprising a 5 kHz sine wave burst lasting for 1 millisecond (5 sine waves, each lasting 200 microseconds). Such bursts repeated once every 40 milliseconds (25 Hz) generating a 24 V peak voltage and 60 mA peak output current.
The device is placed vertically below the chin and stimulations are made until the patient notices contraction of the lower lip on the treated side, indicating location of stimulation over the vagus nerve.
15. Clinical results. A prospective double-blind, sham-controlled studies of nVNS for the acute treatment of migraine was performed, (PRESTO), and the noninvasive neurostimulation for the prevention of chronic migraine (EVENT) trial were performed.
PRESTO included 243 patients with episodic migraine. More members receiving nVNS were pain free at 30 minutes (12.7%) than those receiving a sham treatment (4.2%; P = .01). There was also a greater percentage of the nVNS group who were pain free at 60 minutes (21% vs 10%, respectively; P= .02).
"The PRESTO data suggests that GammaCore was rapidly effective, well-tolerated, and practical for the acute treatment of episodic migraine," principal investigator, Cristina Tassorelli, MD, director of the Headache Science Center at the C. Mondino National Neurological Institute, Pavia, Italy, in a press announcement released in 2017.
In the EVENT study, 59 chronic patients with migraine for prevention treatment formed the study population (GammaCore, n=30 vs sham, n=29). Persistent prophylactic GammaCore use was associated with continued reductions in the number of headache days.
Good luck with this.
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Britt Talley Daniel MD