Headache NewsBlog

Vitamin C is another supplement to consider for pain, immune system (Covid?), connective tissue

By: Dr. Mauskop

29-03-2020

Vitamin C or ascorbic acid (AA) was discovered by Albert von Szent-Györgyi for which he received the 1937 Nobel Prize in Medicine. Linus Poling, one of only 4 people to win the Nobel prize twice, devoted many years of his life to researching AA. A wealth of information on AA is available on Oregon State University’s Linus Pauling Institute website.

Many studies have shown that AA is important in collagen formation. It is also important for the proliferation of stem cells. A study of 1210 hospitalized patients showed that intravenous infusion of AA in doses of 3–10 grams/day reduced the mortality of critically ill patients. AA also plays a vital role in the functioning of the immune system as well as inflammation.

This post was prompted not only by thoughts of how to boost your immunity and increase your resistance to viral infections but also by a recent paper with a catchy title, Dietary ascorbic acid restriction in GNL/SMP30-knockout mice unveils the role of ascorbic acid in regulation of somatic and visceral pain sensitivity. The authors conclude “our data unveil the critical role of ascorbic acid in regulating somatic and visceral pain sensitivity and support accumulating clinical evidence for the usefulness of ascorbic acid in pain management.”

Another example of a basic science study of the role of AA in pain modulation is Evidence for the involvement of glutamatergic system in the antinociceptive effect of ascorbic acid.

And what about migraines? Surprisingly, nobody has done any studies of AA for the treatment of migraines. There is only one case report published in The New England Journal of Medicine describing a 32-year-old man who controlled his migraine headaches with a daily dose of 6 grams of ascorbic acid for six years. He participated in a double-blind study in which he was given either AA or placebo. At the end of 15 days, he correctly identified all days he had received vitamin C and all days he had received a placebo.

How much should you take? The Linus Pauling Institute suggests 400 mg a day, although many popular vitamin C supplements contain 1,000 mg. Taking 1,000 mg is safe, although any amount of AA can cause heartburn or upset stomach because vitamin C is an acid.

Vitamin D is good for pain, immune system (think Coronavirus), brain, and body

By: Dr. Mauskop

23-03-2020

Alternative Therapies, Migraine

Vitamin D level testing is no longer covered by many insurers and many doctors, NY Times, and other media consider taking vitamin D supplements of unproven benefit. I’ve written 10 blog posts over the past 12 years on vitamin D. These posts describe highly scientific studies of the role of vitamin D deficiency on the development of delirium in hospitalized patients, multiple sclerosis, major diseases and dying, and of course migraines.

This morning, Dr. Leo Galland during his TV appearance mentioned the importance of supplements that can boost the immune system and reduce our susceptibility to viral diseases. He mentioned vitamin D and curcumin. Dr. Galland is a highly respected physician who often helps patients with problems that are difficult to diagnose and treat. I’ve reviewed one of his excellent books The Allergy Solution in a previous post.

What prompted another post on vitamin D besides Dr. Galland’s TV appearance, was a 593-patient Mayo Clinic study which reported increased severity of fibromyalgia in patients with vitamin D deficiency. Of these 593 patients, 122 or 21% had vitamin D deficiency. Patients with lower vitamin D levels also reported higher rates of anxiety and depression and were more likely to be overweight.

If you do get your vitamin D level tested, check what the actual result is. The normal range in most laboratories is from 30 to 100. However, if you are at the bottom of the normal range, you may be deficient and be more predisposed to a variety of medical conditions. Keep your level at least in the middle of the range.

100 Migraine Drugs, A to Z: onabotulinumtoxinA

By: Dr. Mauskop

16-03-2020

Chronic migraine

OnabotulinumtoxinA (Botox) is a most remarkable medicine. It was first approved by the FDA in 1989 for two eye conditions and since then it received approval for another dozen conditions as varied as excessive sweating, very frequent urination, spasm of muscles, and of course, migraines.

An interesting chain of serendipitous discoveries led to its approval for migraines. A Vancouver ophthalmologist, Dr. Jean Carruthers started using Botox in 1987 to treat blepharospasm (forceful and uncontrollable blinking) and noticed that patients’ wrinkles disappeared. She mentioned this to her husband-dermatologist Dr. Alastair Carruthers who began to inject it for cosmetic reasons. Then a plastic surgeon in California, Dr. William Binder who has been using Botox to treat wrinkles began hearing from his patient that their headaches went away along with their wrinkles.

When Dr. Binder first presented his observation in the early 1990s, he was met with a lot of skepticism. How could Botox, which affects only superficial muscles and nerve endings, help migraine, which begins deep in the brain? And what does a plastic surgeon really know about headaches? I was also a bit skeptical but faced with many patients whose migraines would not respond to usual treatments, I decided to look into this.

I discovered that by weight, Botox is the deadliest poison known to man. At the same time, it is safer than aspirin, ibuprofen, or acetaminophen because obviously any drug can become a poison depending on the amount you ingest. Thousands of people die every year from bleeding ulcers or kidney problems caused by aspirin and ibuprofen and thousands die from liver damage caused by acetaminophen, but deaths from Botox are extremely rare. Last year I visited Allergan’s manufacturing plant in Ireland where all of the world’s supply of cosmetic and medical Botox is manufactured. On our tour of the plant, we were told that one year’s supply of Botox weighs 1 gram. Each 100-unit vial of Botox contains 5 nanograms (0.000000005 gram) of the toxin.

I was the first neurologist in New York to use Botox for migraines and even though I am a headache specialist and not a plastic surgeon, many of my colleagues were disdainful. Others came to learn the technique I developed. Even before the FDA approval, over 200 doctors from around the world visited our center. It took us a few years to convince Allergan to do clinical trials and then quite a few years to conduct these trials, but in 2010 the FDA approved Botox for the treatment of chronic migraines.

I’ve written several blog posts on the various aspects of Botox therapy including its use off-label (without having an FDA approval) for children with migraines, TMJ disorders, trigeminal neuralgia, post-concussion headaches, common avoidable problems seen with the injections, and about underutilization of this remarkable drug for the treatment of migraines.

Incredibly, the chain of serendipitous discoveries continues – patients treated for migraines reported to feel depressed and this was not because their headaches improved since depression also lifted in patients whose migraines did not improve. And so, this 30-year-old drug continues to find new uses.

Listen to podcast by Bottom Line – 7 New Treatments for Migraines

By: Dr. Mauskop

09-03-2020

Alternative Therapies, Migraine, New treatments

Sarah Hiner, President of BottomLineInc interviews me for The Bottom Line Advocator podcast – 7 New Treatments for Migraines Just Released — with Alexander Mauskop, MD

Galcanezumab can start to improve migraines within a day

By: Dr. Mauskop

08-03-2020

Headache medications, Migraine

Galcanezumab (Emgality) is one of the three injectable monoclonal antibodies approved for the prevention of migraines. Pharmacological studies show that it takes up to a week for these drugs to reach their highest concentration. However, it does not mean that it takes a week for them to start helping. Many of my patients report feeling better within a day. A new study of galcanezumab indicates that such a rapid onset of action is not just due to the placebo effect.

The authors analyzed the results of two large studies of patients with episodic migraines that were submitted to the FDA to gain its approval. The first study enrolled 858 patients and the second, 915. Patients were given monthly injections of galcanezumab 120 mg (with 240 mg loading dose) or 240 mg or placebo for up to 6 months. In both studies, the onset of effect was present the day after the injection.

I do tell my patients that they might start feeling better the day after they receive their first injection (the initial dose of two 120 mg injections), but it is more likely that they will begin to improve within a week or even later. Some patients notice only minimal relief even at the end of the first month and require 2 or 3 monthly shots before any significant improvement occurs. This is true for all three injectable CGRP monoclonal antibodies.

Vyepti, the fourth drug in this family, which was just approved and will be available in a month, is given intravenously. This may result in an even faster onset of action.

Rimegepant, another very safe and effective drug receives FDA approval for the acute treatment of migraine headaches

By: Dr. Mauskop

01-03-2020

Chronic migraine, Headache medications, Migraine, New treatments

Rimegepant (NURTEC ODT) is the second gepant approved for the acute treatment of migraine headaches. It blocks the same CGRP pathway as the injectable monoclonal antibodies that are used for the prevention of migraine attacks (erenumab/Aimovig, fremanezumab/Ajovy, galcanezumab/Emgality, and eptinezumab/Vyepti). It follows the recent introduction of a similar drug that also blocks the CGRP receptor, ubrogepant (Ubrelvy).

Since there have been no head-to-head trials comparing these two gepants, it is had to say if one is better than the other. On average, they appear to be very similar, but this does not mean that they will be equally effective or cause the same side effects in a particular patient. We see this with triptans (drugs like sumatriptan, eletriptan, and other) – the top 5 show similar efficacy in trials, but some patients strongly prefer one over another.

One difference is that rimegepant is an orally disintegrating tablet and does not require water, while ubrogepant is taken with water. This makes rimegepant easier to take on the go and could be easier to take for patients with severe nausea. Another minor difference is that the dose of rimegepant is 75 mg that is taken once a day, while ubrogepant comes in 50 and 100 mg tablets and either dose can be repeated for up to 2 tablets a day. This can be both an advantage and a disadvantage. The instructions are simple for rimegepant – take one tablet once on the day you have a migraine (and the earlier you take any abortive drug the better). With ubrogepant the doctor has to decide whether to give 50 or 100 mg dose and the patient needs to be instructed to take a second dose on the same day (as soon as 2 hours after the first one) if the headache returns or does not completely resolve with the first dose. In clinical trials, this second dose did produce additional improvement.

The safety of rimegepant is as remarkable as that of ubrogepant and the preventive injectable monoclonal antibodies. Rimegepant caused nausea in 2% of patients compared with 0.4% of those on placebo and less than 1% developed a rash or temporary difficulty breathing.

100 Migraine Drugs, A to Z: nortriptyline

By: Dr. Mauskop

26-02-2020

Chronic migraine, Headache medications, Migraine

Nortriptyline (Pamelor) is a tricyclic antidepressant approved by the FDA only for the treatment of depression. However, with the introduction of SSRI family of antidepressants such as fluoxetine (Prozac) which have fewer side effects, the use of tricyclic antidepressants for depression has declined.

Tricyclic antidepressants are still in wide use, but mostly for the treatment of headaches and pain. Nortriptyline is very similar to amitriptyline (Elavil) and is thought to cause fewer and milder side effects, although this has not been proven. This could be due to the fact that amitriptyline is broken down into nortriptyline, which is the active metabolite. Amitriptyline tends to be more sedating, which can be useful in patients with insomnia.

There are no good blinded studies of nortriptyline for the prevention of migraines and they are not likely to be done. We assume it is as good as amitriptyline, although studies of amitriptyline also lack in size and scientific rigor.

There are many trials of amitriptyline and nortriptyline for various pain conditions, but they are also not up to our modern standards. Amitriptyline was approved in the US in 1961.

Besides sedation, nortriptyline can cause dry mouth, constipation, urinary retention in older patients, and other side effects. The dose to treat migraines and pain is usually lower than the dose used to treat depression. Pain and headaches sometimes respond to as little as 10 or 25 mg while for depression, the dose goes up to 100 mg and higher.

In short-term studies of major depression, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults. This is less likely to occur when treating pain, but many pain patients also experience depression.

Vyepti – Another breakthrough in the prevention of migraines

By: Dr. Mauskop

22-02-2020

Chronic migraine, Headache medications, Migraine

Eptienzumab (Vyepti) was just approved by the FDA for the preventive treatment of migraine headaches. Eptinezumab is another monoclonal antibody that blocks the effect of CGRP, a chemical released during a migraine attack. It joins erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), three other monoclonal antibodies approved for the preventive treatment of migraine headaches.

Eptinezumab is different from the other three drugs in that it is administered intravenously. It is given every three months by an infusion over 30 minutes. The other three drugs are self-administered subcutaneously every month, although fremaezumab can be also given every 3 months.

Eptinezumab may also have a faster onset of action because it is administered intravenously and quickly reaches its peak concentration in the blood. The other three drugs take up to a week to reach their maximum concentration. The reason for such a long delay (most drugs injected subcutaneously take less than an hour to peak) is that the monoclonal antibodies are large molecules and are distributed not by blood vessels, but the slow-moving lymphatic system. On the other hand, these are preventive therapies, so the speed of onset is less critical than for abortive drugs, such as NSAIDs, triptans, and gepants (ubrogepant, rimegepant).

Theoretically, it is possible that eptinezumab could work for patients who do not respond to the other three drugs because of a better distribution of the drug and because these drugs are not identical. About 10% of my patients report significantly better response when switched from erenumab, which was first to be approved, to either fremanezumab or galcanezumab.

We don’t know yet what the drug will cost and how well the insurance companies will pay for it. All three subcutaneous drugs cost about $650 a shot and all three manufacturers offer a one-year free trial if the insurance refuses to pay. This does not apply to patients who have Medicare or Medicaid, which do not allow free trials or discount coupons. Fortunately, more and more insurers, including the government plans, are covering these drugs, albeit with some paperwork that needs to be completed by the doctor. The cost of eptinezumab will consist of two parts – the cost of the drug and the cost of the infusion.

fMRI may offer the first accurate and objective way to diagnose migraines

By: Dr. Mauskop

18-02-2020

Migraine, Science of Migraine

A group of American and Chinese researchers reported an objective way to diagnose migraine headaches using functional magnetic resonance imaging (fMRI). The paper just published in Neurology used machine learning to examine differences between the brains of migraine sufferers, patients with chronic pain, and healthy controls.

MRI scans of migraine patients typically show normal brain structure. fMRI scans can visualize connections between different parts of the brain, or so-called connectome. The researchers discovered abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that allowed them to distinguish migraineurs from healthy controls with 93% sensitivity and 89% specificity. They verified the specificity of this diagnostic marker with new groups of migraineurs and patients with other chronic pain disorders (chronic low back pain and fibromyalgia) and demonstrated 78% sensitivity and 76% specificity for discriminating migraineurs from nonmigraineurs. They also found that the changes in the marker correlated with the changes in headache frequency in response to real acupuncture.

If confirmed, these findings could offer a very accurate way to diagnose migraine, rather than relying on subjective clinical description. This test could also allow for an objective way to test various new treatments. Because of the cost of fMRIs, it will be a long time before it becomes a routine clinical test. It is also possible that genetic testing and testing of blood samples for biochemical markers will lead to other accurate diagnostic tests and tests to predict responses to various therapies.

Acupuncture for migraines – worth a try

By: Dr. Mauskop

14-02-2020

Alternative Therapies, Migraine

Acupuncture has been subjected to a very large number of clinical trials for a variety of conditions, including migraine headaches. Dr. Zhang, a neurologist at Stanford and two of his colleagues have published a review of trials that compared acupuncture with standard pharmacological migraine therapy.The review included only scientifically rigorous trials that compared the efficacy of acupuncture with a standard migraine preventive medication in adult patients with a diagnosis of chronic or episodic migraine with or without aura.

Out of the 706 published reports, 7 clinical trials, with a total of 1430 participants were of high quality. Modes of acupuncture and pharmacological treatments varied from trial to trial, which made it difficult to make any sweeping conclusions. However, several of the studies showed acupuncture to be more effective than the standard pharmacological treatments for migraine prevention.

Even if acupuncture is only as effective as drugs, its safety makes it a superior choice. The major drawbacks of acupuncture are that it is time-consuming and relatively expensive when compared to generic prescription drugs. These are the reasons why I rarely perform acupuncture on my patients. If someone is interested in acupuncture, I do encourage them to try it and refer them to well-trained lower-cost non-physician providers.

100 Migraine Drugs, A to Z: nebivolol

By: Dr. Mauskop

10-02-2020

Headache medications, Migraine

Nebivolol (Bystolic) is one of the newer, third generation beta-blockers, drugs used for the treatment of high blood pressure as well as migraine headaches. In Europe, it’s been in use for over 20 years.

In addition to beta-blockade, it may have additional beneficial effects on endothelium (blood vessel lining). It may also improve glucose metabolism by improving insulin sensitivity and other functions.

Nebivolol has the advantage of having fewer side effects than other beta blockers. including lower rates of fatigue and shortness of breath.

The majority of migraine sufferers are young women, many of who have low blood pressure, which predisposes them to side effects from beta blockers.

However, in the US, nebivolol is relatively expensive ($160 for one month supply) since it is not yet available in a generic form. Many insurers will not pay for it unless the patient cannot tolerate the widely used and inexpensive beta blockers such as propranolol, metoprolol, or atenolol.

Lasmiditan – another new drug for acute treatment of migraines.

By: Dr. Mauskop

02-02-2020

Headaches, Migraine, New treatments

Lasmiditan (Rayvow) is the first (and probably the last) drug in the class of ditans. Just like the triptans (sumatriptan or Imitrex and other), it works through the serotonin system. However, it activates 5-HT_1F serotonin receptor, while triptans activate 5-HT_1Band 5-HT_1Dreceptors. This confers an advantage in that lasmiditan does not cause constriction of coronary arteries, which can happen with triptans . So patients with a history of a heart attack, angina or multiple risk factors for vascular disease who could not take triptans, now have another drug that is safe to use. The first acute migraine drug for this at-risk population, ubrogepant (Ubrelvy) became available a week ago. Lasmiditan will reach pharmacies in the next few days.

I will also prescribe lasmiditan to patients for whom triptans and ubrogepant are ineffective, partially effective, or cause side effects, which constitutes a sizable minority of my patients. .

Results of two large double-blind trials showed that 28-39% of patients achieved fast and complete elimination of migraine pain at two hours with lasmiditan as compared to 15% and 21% with placebo. 41-49% of patients achieved freedom from their most bothersome symptom of sensitivity to light, sensitivity to sound, or nausea at two hours with lasmiditan compared to 30% and 33% with placebo.

Lasmiditan is available in 50 mg and 100 mg tablets and the recommended dose is 50, 100, or 200 mg taken once a day.

Side effects were generally mild to moderate and the most frequent ones included dizziness, fatigue, tingling, drowsiness, nausea, and muscle weakness. Two driving studies showed that lasmiditan may cause significant driving impairment.

Lasmiditan is a non-narcotic medication, has low abuse potential and no evidence of physical dependence. It is a controlled substance but is in category 5, which indicates the lowest level of potential risk of abuse.