Migraine | Headache NewsBlog

100 Migraine Drugs, A to Z: metoclopramide

By: Dr. Mauskop

19-04-2020

Headache medications, injections, Migraine

Metoclopramide (Reglan) is an anti-nausea drug that has been in use since 1979. Controlled studies have shown that metoclopramide stops not only nausea and vomiting that often accompany migraine attacks, but also relieves the pain.

The American Headache Society (AHS) and the European Federation of Neurological Societies (EFNS) guidelines on the management of adults with acute migraine recommend intravenous metoclopramide as an effective and recommended treatment in the management of acute migraine. While intravenous (IV) administration is preferred, intramuscular (IM), subcutaneous (SC) and oral routes are also effective.

These guidelines were based on many high-quality blinded studies such as one comparing 10 mg of IV metoclopramide with 600 mg of ibuprofen in which metoclopramide was clearly superior. A meta-analysis of 13 studies of intravenous metoclopramide involving 655 patients showed that “Metoclopramide is an effective treatment for migraine headache..” and that “Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments”. Another emergency room study that was done after this meta-analysis was published, compared IV metoclopramide with IV ketorolac (an NSAID pain drug) and IV valproate, (an epilepsy drug approved in a pill form for the prevention of migraines) in 330 patients. Metoclopramide was the most effective of the three.

We give IV metoclopramide in the office and prescribe it in a tablet form. However, this drug is not free of side effects. Drowsiness is one of the common side effects, but a much more unpleasant side effect is severe restlessness or akathisia. Some patients describe it as wanting to crawl out of their skin, being very restless and very uncomfortable. This side effect can be relieved by diphenhydramine (Benadryl) given IV or as a tablet. According to one study, the incidence of this side effect is 6% if the IV infusion is given over 15 minutes and 25% if given as a “push” in under a minute. We usually give it as a “push” and find that significantly fewer than 20% of patients develop this side effect.

A much more serious side effect of metoclopramide is tardive dyskinesia or involuntary movements of the mouth, face or another part of the body. The FDA warning states in part:
“The development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time. Tardive dyskinesia is rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped”. A recent review estimates that tardive dyskinesia happens in less than 1% of patients.

This very rare but devastating side effect is not likely to occur in our patients who receive this drug very infrequently, only for emergencies. However, the thought of tardive dyskinesia is always lurking in the back of our minds so we tend to use IV ondansetron (Zofran) to treat nausea. Ondansetron does not help with pain and we have to combine it with IV ketorolac (Toradol) or another drug, but it is safer.

Covid-19 and headaches

By: Dr. Mauskop

10-04-2020

Botox, Chronic migraine, Migraine

It is hard to think or write about anything other than Covid-19, so here is some information on Covid-19 and headaches.

The bad news is that the long-suffering headache patients are suffering more. Most hospitals consider Botox injections, nerve blocks, and other procedures to treat headaches as “nonessential”. Yes, our patients will not die like some of those with Covid-19, but a more nuanced approach than just canceling all “nonessential” procedures should’ve been possible. My NYC colleagues are not needed to treat Covid-19 patients and they are just sitting around worrying about their patients and their own futures. We are a private headache clinic and are continuing to see patients in our office (with all the precautions) for Botox and other procedures, although the number of patients we are treating has dropped by three quarters. Most are understandably concerned about contracting the virus and are staying home.

As far as the relationship between Covid-19 and headaches, it appears that this virus can sometimes invade the brain. This is not surprising because many viruses that affect the respiratory system can also affect the brain. The brain symptoms of Covid-19 are similar to those seen with other brain infections, including headaches (at times with nausea and vomiting), seizures, and disturbed consciousness. Loss of sense of smell is very characteristic of Covid-19 and it happens because of the damage to olfactory nerves. These nerve endings line the nasal cavity and they are directly connected to cell bodies of neurons in the brain. This is one of the possible routes of entry of the virus into the brain.

Recent reports suggest that Covid-19 causes blood clotting in small blood vessels of the lungs, which may be contributing to deaths in some patients. A few cases of strokes in Covid-19 patients have been reported, although it is not clear if blood clotting or even the virus itself were responsible. The Mt. Sinai Hospital system to which I belong just issued guidance for the use of blood thinners in Covid-19 patients. This could be life-saving for some critically ill people.

All this may sounds very alarming, but fortunately, most neurological and other symptoms of Covid-19 resolve in over 99% of patients. The mortality rate of Covid-19 seems higher than 2% only because there are so many people who had the infection with mild or no symptoms and those people are not included in the calculations of mortality rates.

One silver lining is that now we all practice telemedicine. The technology has existed for years, but a major obstacle has been the unwillingness of insurance companies to pay for telemedicine visits. The telehealth parity law was actually passed in NYS in 2016. This pandemic will make televisits much more commonplace. Telehealth law excludes audio-only and electronic messaging-only. Fortunately, there are several HIPAA-compliant video platforms that make televisits easy to conduct. Less than half of our patients need to be in the office for a procedure while the rest can be safely and effectively treated remotely. Most people have busy lives and not having to trudge to the office will save them hours of time.

Nerivio, a drug-free treatment for acute migraines

By: Dr. Mauskop

04-04-2020

Alternative Therapies, Migraine, New treatments

Nerivio is a smartphone-controlled wireless device that provides electrical stimulation of the type that is similar to TENS units widely used in physical therapy for musculoskeletal disorders. It was approved by the FDA last year for the treatment of acute migraines.

Nerivio was proven to be effective in a double-blind, sham-controlled study of 252 adults with migraine headaches. It was applied for 40 minutes on the upper arm and the strength of the current is gradually increased to a strong but non-painful intensity level. Active stimulation was more effective than sham stimulation in achieving pain relief (67% vs 39%), pain-free state (37% vs 18%), and relief of the most bothersome symptom such as nausea sensitivity to light or noise (46% vs 22%) at 2 hours post-treatment. The pain relief and pain-free superiority of the active treatment was sustained 48 hours post-treatment. The device was very well tolerated with only a few patients reporting local irritation.

This device is controlled by a smartphone which allows the manufacturer to collect data about its use (with patients’ permission and without identifying individual patients). After 6 months of my prescribing this device to a couple of hundred of patients, 62% of my patients reported having pain relief after 2 hours and 24% reported to be pain free after 2 hours. These numbers are comparable to the results seen with migraine drugs such as triptans (sumatriptan or Imitrex and other) as well as the new class of abortive migraine drugs, gepants (ubrogepant or Ubrelvy and rimegepant or Nurtec ODT). One big advantage of Nerivio is that it is not ingested and is much less likely to cause any side effects.

Theranica, the manufacturer of Nerivio is working to expand the indications for the device by conducting trials in adolescents and patients with chronic migraines.

Nerivio is not covered by most insurance companies and costs $99 for each disposable device which provides 12 treatments. It is available only by prescription. If you have difficulty finding a headache specialist, since the start of the pandemic we have begun to offer telemedicine visits using HIPAA-compliant platform. You can call our front desk (212-794-3550) to schedule an appointment.

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

By: Dr. Mauskop

29-03-2020

Alternative Therapies, Migraine

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.

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.