Archive
Migraine

Dr. Brian Loftus, a Texas neurologist, alerted me to the possibility that the shortening of the effect of Botox can be reversed by taking a zinc supplement. Dr. Loftus shared an unpublished report by Houston physicians who showed that zinc supplementation can extend the effect of Botox.

There is a good theoretical reason to suggest that for Botox to work, you need to have sufficient amounts of zinc. You can read about this connection in a review article by one of the leading movement disorders specialist, Dr. Mark Hallet.  He concludes that “Toxins are zinc dependent proteases, and supplemental zinc may produce a greater effect.”

It is very likely that taking zinc will benefit mostly people who are deficient. I just saw a patient in whom Botox provides relief for only 2 months and whose blood test showed a low zinc level. I suggested that he takes 50 mg of zinc every day.

Zinc is necessary for the activity of over 100 different enzymes that are involved in vital chemical processes of the body. Zinc is involved in the immune system, growth of cells, building proteins, and many other functions.

We might consider adding zinc to the usual battery of tests done on the first visit to our clinic. These include RBC magnesium, vitamins B12 and D, and routine blood tests.

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Patients with chronic migraine who were started on Botox were significantly more likely to continue to be treated with Botox after one year than patients who were started on a CGRP monoclonal antibody (mAb). mAbs are given monthly by injection. This category includes erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality).

The results of this large retrospective study that included 1,974 patients were presented at the last meeting of the American Headache Society held in June of this year. The lead authors were Dr. Todd Schwedt of the Mayo Clinic and Dr. Andrew Blumenfeld.

The study was sponsored by the manufacturer of Botox which makes it inherently biased. However, the difference between the two groups was striking. Of patients who were started on Botox, 66% continued the treatment at the end of the year. Less than a third of patients who were started on a mAb were still getting it at the end of the year.

The researchers looked at differences in outcomes in patients enrolled before and during COVID. The results were similar before and during the pandemic. This is surprising because, during the pandemic, many patients were reluctant to come to the office for Botox injections. Many preferred to self-inject mAbs at home. Despite this obstacle, Botox patients were twice as likely to continue treatment at the end of the year.

Besides efficacy, the major reason I recommend Botox ahead of mAbs and other drugs is its proven long-term safety. Botox was first approved by the FDA in 1989. Botox is my preferred treatment for chronic migraines even in pregnant women.

Both mAbs and Botox are fairly expensive. The same group of researchers presented a second study that evaluated all-cause and migraine-related costs in these two groups of patients. They found no difference in total healthcare costs and migraine-related costs, including emergency department expenses.

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Last week I spoke to Dr. Amelia Scott Barrett, a neurologist and headache specialist based in Denver. She shares my interest in combining medications with various non-drug therapies. In our first conversation, we discussed the role of magnesium in treating migraines.

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The 6th Annual International Headache Symposium in Israel will be held at Daniel Hotel, Herzliya (8 miles from Tel Aviv), on October 27, 2022. THe symposium is organized by the President of the Israeli Headache Association, Dr. Oved Daniel and by Dr. Arieh Kuritzky.

I am honored to have been invited to speak alongside the President of the International Headache Society Dr. Messoud Ashina, Dr. Rami Burstein of the Harvard Medical School, and other leading headache experts. The topic of my presentation will be “What to do when nothing works”. Other topics to be discussed include, Molecular signaling pathway in migraine: update, (Messoud Ashina), Connecting the line between dizziness, occipital headache, muscle tenderness and the cerebellum (Sait Ashina), Open-label studies: do they have any value? (Cristina Tassorelli), and others.

You can see the full program and registration information on this website.

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Regular intravenous infusions of magnesium prevented migraines in five children, according to a report presented at the annual meeting of the American Headache Society by A.J. Freed and S. Sahai-Srivastava. The children were between the ages of 11 and 16. Four of them had the diagnosis of chronic migraines and one, episodic. Two of them continued to have daily headaches but they were mild with the infusions. The other three also had a significant drop in the number of headache days.

Over the past 30 years, we’ve given monthly infusions to thousands of patients, including children as young as 6. Genetic factors play a role in some patients with magnesium deficiency. We’ve had three generations of a family coming for monthly infusions. Besides genetics, other reasons for magnesium deficiency include stress, alcohol, gastrointestinal disorders, poor diet, and others.

About half of migraine sufferers are deficient. They are likely to respond to oral magnesium supplementation. Many, however, do not absorb magnesium taken by mouth. If we know that a patient is deficient because they have other symptoms of magnesium deficiency (cold extremities, muscle cramping, PMS, palpitations, brain fog, and others) or because their blood level (RBC magnesium) is low or is at the bottom of the normal range, we give magnesium intravenously.

If you cannot find a doctor who gives infusions of magnesium, you may want to search for an infusion center or an urgent care facility that would do it. In many large cities, magnesium and vitamin infusions are done at some spas. There are also companies that offer home visits by a nurse.

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Two out of three women stop having migraines during pregnancy, especially in the second and third trimester. The difficult question is how to treat migraines in the first trimester and in women whose migraines do not improve or get worse in pregnancy.

Acetaminophen (Tylenol, paracetamol) is considered safe in pregnancy and that is what many women take for migraines and other pains. Unfortunately, acetaminophen is usually ineffective for severe migraines. It is also not as safe as many physicians and the general public thinks. Several studies indicate that acetaminophen increases the risk of attention-deficit hyperactivity disorder (ADHD) and with heavy use, possibly even autism spectrum disorder.

Some obstetricians strongly advise against taking any migraine medications. However, the stress of an acute migraine attack with severe pain, vomiting, and dehydration is likely to have a deleterious effect on the fetus. A Danish study of 22,841 pregnancies among women with migraine showed that untreated migraine leads to an increased risk of low birth weight, preterm birth, and cesarean delivery.

A report just published in the journal of the American Medical Association (JAMA) examined “Association of Maternal Use of Triptans During Pregnancy With Risk of Attention-Deficit/Hyperactivity Disorder in Offspring”.

The study used the data from the Norwegian Mother, Father and Child Cohort Study, linked to the Medical Birth Registry of Norway, the Norwegian Patient Registry, and the Norwegian Prescription Database using the mother’s personal identification number. The conclusion of this large and rigorous study was: “This cohort study found no association between prenatal triptan exposure and ADHD diagnosis or ADHD symptoms at 5 years of age. This study adds to the growing literature on the safety of triptan use during pregnancy and expands it to an important neurobehavioral outcome.”

Triptans have been available without a prescription in all European countries for over a decade. In the US, triptans are available only by prescription. This is one of the reasons for the perception of acetaminophen as being more benign than sumatriptan and other triptans. The opposite is likely to be true. If you are a pregnant woman suffering from severe migraines, ask your doctor for a prescription for sumatriptan.

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With tens of millions of Americans suffering from migraines, access to care is a major problem. Cove, a telemedicine startup, offers a practical and affordable solution. They deliver evidence-based therapies to patients in need. To prove that their approach works, Cove collects and analyzes vast amounts of data. The study I just presented at the annual scientific meeting of the American Headache Society shows that with Cove underserved minorities obtain excellent outcomes that are equal to those of whites.
Disclosure: I am a paid consultant to Cove.

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A paper presented at the annual meeting of the American Headache Society that is taking place this weekend examined the risk of major adverse cardiovascular events (MACE) in patients with preexisting cardiovascular (CV) conditions. The researchers compared the risk of triptans with that of opioid/barbiturate drugs (drugs like codeine, Vicodin, Percocet, Fioricet) and non-steroidal anti-inflammatory drugs (NSAIDs).

They used Mass General Brigham Research Patient Data Registry database to identify 12,121 prescriptions. Of these, 33% were for triptans, 50% for opioid/barbiturate drugs, and 17% for NSAIDs.

MACE occurred in 1% of those taking triptans, 4.5% taking opioid/barbiturate drugs, and 3.8% taking NSAIDs.

This goes against the established dogma of avoiding triptans in patients with CV problems. Instead, doctors are advised to offer opioid/barbiturate drugs or NSAIDs. Unfortunately, according to the FDA-approved package insert, triptans are contraindicated in patients with CV, cerebrovascular, and peripheral vascular problems. This contraindication came about from purely theoretical reasoning rather than real-life experience. Triptans do in fact have mild vasoconstriction properties and it is possible that someone with severe occlusion of coronary or other blood vessels can have dangerous constriction of a blood vessel. There have been also reports of healthy people developing cardiovascular complications, but those are very rare.

This new data indicates that triptans are safer than the alternatives most doctors prescribe. The two alternatives described in the report also carry significant risks of addiction, stomach ulcers, and bleeding. It is very likely, however, that doctors will continue to avoid prescribing triptans in this population because of legal concerns and ingrained habits.

We do have two new classes of drugs to treat an acute migraine attack that are proven to be safe in patients with CV conditions. These are gepants – rimegepant (Nurtec) and ubrogepant (Ubrelvy) as well as ditans – lasmiditan (Reyvow). These drugs are very expensive and insurers always require that patients first try other drugs.

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Not surprisingly, none of the new migraine drugs have been tested in pregnant women. No new drug for any indication is ever tested for its safety in human pregnancy. They are always tested in pregnant animals, which helps weed out most drugs that are clearly dangerous. It takes decades to learn if a drug is safe. This happens through an accumulation of anecdotal reports and pregnancy registries that are usually run by drug manufacturers.

Erenumab (Aimovig) was the first CGRP monoclonal antibody to be approved for the preventive treatment of migraines four years ago. It was tested in pregnant monkeys who were given 50 times higher doses (by weight) than the FDA-approved dose for humans. Even though some of the medicine crossed the placenta into baby monkeys, they had no developmental problems.

In the current issue of Headache, University of Texas doctors published a report of a woman who continued to inject herself with erenumab throughout the duration of her pregnancy. She tried to stop the drug before planning to get pregnant but her severe migraines recurred. Her baby was born healthy and had normal development by the last evaluation at 6 months of age.

This case report is the first very small but important step in the process of evaluating the safety of erenumab in pregnancy.

In humans, the transfer of antibodies, which are large molecules, across the placenta is very limited before the 16th week of pregnancy and increases after the 22nd week. We still recommend stopping the drug about five months before a pregnancy is planned. If a woman, however, does get pregnant, intentionally or not, the risk of complications is low if erenumab is stopped within the first three months of pregnancy. This also applies to all other monoclonal antibodies in general and specifically other migraine drugs – galcanezumab (Emgality), fremanezumab (Ajovy ), and eptinezumab (Vyepti).

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Rimegepant (Nurtec ODT) was just approved by the European Medicines Agency for marketing in 27 EU countries as well as Iceland, Liechtenstein, and Norway. It was approved for both the acute treatment of migraine with or without aura, and prophylaxis (prevention) of episodic migraine in adults who have at least four migraine attacks per month. The drug will be sold under the name VYDURA.

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If you are “overusing” acute migraine medications, preventive migraine treatments still work very well. This was the conclusion of a study that was just published in the journal of the American Academy of Neurology, Neurology.

The concept of medication overuse headache (MOH) has remained controversial. The majority of headache specialists believe in its existence. And that is what it is, a belief. There are correlational studies showing that those who take acute migraine drugs tend to have them more often as time goes on. This obviously does not mean that the drug is responsible for the increase in frequency. It is more likely that people take drugs more often because their headaches have gotten worse. There is proof for the existence of MOH only for two drugs – caffeine and opioid (narcotic) pain drugs. Triptans and NSAIDs have no such proof and in my 30 years of experience, they rarely cause MOH.

The daily use of triptans is the topic of my most popular post in the 15 years of writing this blog. It received about 400 comments. Many people commented how relieved they are that taking triptans daily can be safe and effective. They often lament that they can’t get their doctors to prescribe a sufficient quantity of pills.

I am not suggesting that taking triptans daily is the first or second option. It is always better to try Botox and non-drug approaches. Taking a triptan daily, however, is probably safer than taking FRA-approved epilepsy drugs such as topiramate (Topamax) or divalproex (Depakote), or even an antidepressant.

The article in Neurology describes a large study with over 700 participants who were “overusing” acute migraine medications. Half of them were taken off these drugs and started on preventive therapies and the other half were given preventive therapies without stopping acute drugs. Both groups did equally well. This goes against the old dogma that preventive therapies will be ineffective if the daily abortive drugs are not stopped first. The most common preventive treatments in this study were topiramate, Botox, and amitriptyline (Elavil).

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Yesterday I saw a 48-year-old man who has been suffering from migraine headaches since his teens. He did not respond to a wide variety of drugs and non-drug therapies, but Emgality has been very effective. The only problem is that the effect lasts three and a half weeks. During the week before the next shot, his migraine headaches become severe and frequent. Sumatriptan helps but his disability as measured by the MIDAS scale is in the moderate range. He is a high-level executive in a large corporation and needs better control of his migraines. He had tried the other two monoclonal antibodies for migraines – Aimovig and Ajovy – and they were less effective.

Fortunately, there is a good solution to his problem. I advised him to take Emgality injections every three and a half weeks. This is a higher frequency than what is recommended by the FDA and some doctors and patients may have concerns about the safety. The one-month interval is based on averages derived from large studies. People, however, are not average. Some metabolize drugs faster or need a higher or a lower dose of a drug. Another reassuring fact about Emgality is that it is approved at a much higher dose for cluster headaches. For migraine, we give a 240 mg loading dose and then, 120 mg monthly. Patients with cluster headaches get monthly injections of 300 mg.

I have patients who have the same problem of the short duration of effect with Aimovig and Ajovy as well.

A major obstacle to the more frequent use of these drugs is the fact that insurance companies will only pay for 12 shots a year. These drugs cost about $600 to $700 a dose, so the cost is a major factor for many people. The way I get around it is by providing patients with free samples. Because we have three similar competing drugs, we get samples of all three. If you are having a similar problem, ask your doctor for a free sample. Some academic centers and large hospitals do not allow doctors to receive samples but most doctors in private practice can get them.

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