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Migraine

Migraine can be triggered by many foods, including sugar, chocolate, smoked, pickled, cured, dried, and fermented foods. There are also foods that can help with migraines. These are magnesium-rich dark leafy vegetables and whole grains. Omega-3 fatty acids that are known to have anti-inflammatory properties is another option.

The British Medical Journal just published a randomized controlled trial of omega-3 and omega-6 fatty acids in the prevention of migraines. The same group of North Carolina researchers published a similar smaller study in 2013.

The new trial included 182 participants who had migraines on 5-20 days per month. They were divided into three groups. One group was supplemented with omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The second group was also given the same amount of EPA and DHA but their diet also had a reduced amount of linoleic acid, an omega-6 fatty acid. The third group served as control.

Compared with the control diet, the first two diets decreased total headache hours per day, moderate to severe headache hours per day, and headache days per month. The diet that increased omega-3s and reduced omega-6 had a greater decrease in headache days per month than the diet that was only supplemented with omega-3s.

Supplementation also resulted in an improvement of inflammatory markers in the blood, a change that was not seen in the control group.

If eating more salmon or other fish rich in omega-3s is not practical, taking a good-quality supplement is a good alternative. To reduce your omega-6 intake avoid processed seed and vegetable oils and processed foods that contain them.

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In the US, we are lucky to have seven different triptans available in the pharmacies. Five of them – sumatriptan, rizatriptan, zolmitriptan, eletriptan, and almotriptan are considered to be more effective than the other two – naratriptan and frovatriptan. Frovatriptan has the longest duration of effect because its half-life is 26 hours. Its initial efficacy, however, is not as good as that of other triptans. Naratriptan has a half-life of 6 hours, while the leading five triptans, only 2-4 hours. Naratriptan is also considered to be less effective but it could be because the marketed dose is too low.

In an article in the latest issue of Cephalalgia Peer Tfelt-Hansen argues that naratriptan is as effective as sumatriptan. In fact, if you inject an adequate dose of naratriptan it works better than an injection of sumatriptan. Naratriptan, however, is not available as an injection, only sumatriptan is.

Naratriptan (Amerge) was introduced by the same company that made sumatriptan (Imitrex), the very first triptan. They decided to market it as a “gentle” triptan and selected a relatively low dose of 2.5 mg that had as few side effects as the placebo.

In clinical trials, 2.5 mg of oral naratriptan is less effective than 100 mg of oral sumatriptan. However, clinical trials have shown that 10 mg of naratriptan has similar efficacy to 100 mg of sumatriptan. Naratriptan, 10 mg had slightly fewer side effects than sumatriptan, 100 mg.

The author also mentions the conclusion of the 2004 review by the American Triptan Cardiovascular Safety Expert Panel: “Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low”. For more than a decade now, all European countries have at least one of the triptans available without a prescription.

The practical implication of this information is that it is safe to exceed the FDA-approved dose of naratriptan. If taking one 2.5 mg tablet provides some relief, taking two or three at once will not result in dangerous side effects. I’ve also had patients tell me that they need to take a double dose of sumatriptan – 200 mg instead of 100 or 20 mg of rizatriptan instead of the maximum recommended single dose of 10 mg. In the US, eletriptan is available only in 20 and 40 mg strength. Some European countries have 80 mg tablets as well.

Since all triptans are now available in a generic form, three of them are very inexpensive and patients can bypass the insurance limits and pay out-of-pocket for additional tablets. That is if your doctor is willing to prescribe a larger number of tablets – many erroneously believe that triptans are a common cause of medication overuse, or rebound headaches. You can find naratriptan, rizatriptan, and sumatriptan in some pharmacies for less than $2 a pill.

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It’s been a few years since I wrote about meditation. There is little doubt that it helps migraine sufferers. Unlike drugs, meditation is harder to test in clinical trials. However, we do have many imaging studies showing the effect of meditation on the brain and specifically on pain.

Mindfulness-based stress reduction (MBSR) is based on the practice of meditation. It is more structured and usually consists of a fixed number of sessions. This makes it easier to study in research trials.

The results of such a clinical trial were recently published in JAMA Internal Medicine. The researchers compared MBSR with headache education. The study included 89 adults who experienced between 4 and 20 migraine days per month. The participants and the researchers analyzing the data were blinded as to which group patients were assigned to.

MBSR or headache education was delivered in groups that met for 2 hours each week for 8 weeks. Most participants were female and the mean number of migraine days per month was 7. They had severe migraine-related disability. The follow-up period was 36 weeks.

While MBSR did not improve migraine frequency more than headache education, it did improve disability, quality of life, self-efficacy, pain catastrophizing, and depression for up to 36 weeks.

MBSR courses are widely available online. However, you can also learn to meditate by reading a book. My favorite one is Mindfulness in Plain English by B. Gunaratana. In-person classes are also becoming again (after COVID) widely available. Tara Brach is a psychologist and a Buddhist who has a very good free meditation podcast. Many people like using apps. Headspace, Calm, and Ten Percent Happier are some of the more popular ones.

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The international classification of headache disorders lists many different types of migraines – migraine with aura, hemiplegic, retinal, chronic, and others. Chronic migraine is present if a person has a headache on 15 or more days each month. If the headache is present on fewer than 15 days, the condition is called episodic migraine.

The division into chronic and episodic migraine is not based on any scientific evidence. Research by Dr. Richard Lipton and his colleagues showed that patients often cycle from chronic into episodic migraines and back. This happens even without any treatment.

An international group of headache experts (some of whom participated in the decision to split migraines into chronic and episodic) just published a repudiation of this arbitrary designation.

They concluded: “Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients.”

One damaging aspect of having a category of chronic migraine as it applies to clinical practice is the fact that Botox is approved only for chronic migraines. I know from 25 years of experience injecting Botox that it works very well for some patients who have as few as four migraines a month. Unfortunately, insurance companies do not pay for Botox unless you have chronic migraine. This deprives many patients of this very effective and safe treatment.

The second very costly effect is on the research of new preventive drugs. The FDA requires a separate set of studies for chronic and episodic migraines. These additional trials of the four approved injectable CGRP monoclonal antibodies added many millions of dollars to the development costs. The trials showed good relief for both episodic and chronic migraine sufferers.

Hopefully, the next, fourth classification of headache disorders will eliminate the category of chronic migraines.

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A publication of the American Headache Society, Headache, The Journal of Head and Face Pain, has just published Dr. Allan Purdy’s most generous review of my new book, The End of Migraines: 150 Ways to Stop Your Pain.

I am very grateful to Dr. Purdy and to my many colleagues who wrote endorsements for this book.

Self-publishing allows me to set a low price of $3.95 for the ebook version. It also makes it easy for me to regularly update it. Self-publishing, however, means that, unlike my previous three books, this one does not have the promotional help of a big publisher. If you read the book, please write a review on Amazon and spread the word to other migraine sufferers.

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Biohaven, the manufacturer of rimegepant (Nurtec ODT) just received FDA approval to market this drug for the prevention of migraines. Rimegepant was approved in January of 2020 for the acute treatment of migraine headaches. It is the first drug to be approved for both acute and preventive therapy of migraines.

Rimegepant is one of six drugs that block the action of calcitonin gene-related peptide (CGRP). CGRP has many important functions in the body but the release of excessive amounts of it in the brain can trigger a migraine. Four of the CGRP migraine drugs are given by injection and they are used only for the prevention of migraine attacks. Rimegepant and ubrogepant (Ubrelvy) are taken by mouth as needed, whenever a migraine strikes. These are truly novel drugs that have dramatically improved the lives of many migraine sufferers.

Rimegepant stays in the body longer – it has a half-life of 10-12 hours, while ubrogepant’s half-life is 7-8 hours. Another difference is that rimegepant dissolves in your mouth (ODT after Nurtec stands for orally disintegrating tablet), while ubrogepant is a solid tablet that is swallowed.

In clinical trials, rimegepant was noticed to provide relief of migraine that persisted for up to 48 hours. Because of this sustained effect, the researchers decided to test this drug for the prevention of migraine attacks by giving it every other day. And rimegepant passed this test. The official FDA-approved label says that for the prevention of migraines, one tablet of rimegepant should be taken every other day. For the acute treatment of migraines, the directions say to take 1 tablet a day, as needed.

The insurers typically pay for 8 tablets a month, although a few of my patients have been able to get 16. Now, with its approval for the prevention, patients will be able to get 16 tablets a month. It is possible that some patients may be able to get an additional 8 tablets for acute therapy. For most, however, 16 tablets a month should be sufficient.

The safety profile of rimegepant (as well as ubrogepant) is truly remarkable. The new rimegepant label states that “The most common side effects of NURTEC ODT were nausea (2.7%) and stomach pain/ indigestion (2.4%).” It also states that these are not the only possible side effects but their frequency is very low. Just like with any drugs, an allergic reaction is also possible.

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The opioid epidemic has claimed many lives. Overprescribing by doctors has certainly played a role. The push to use opioids more liberally started in the late 1980s. This promotion by many pain experts even led to pain being adopted as the fifth vital sign. One impetus for this push was the mistaken belief in the low rates of addiction when opioids are used to treat pain. Another was the results of surveys of patients being discharged from hospitals. Poor pain control was the main complaint of 40% of such patients. Centers for Medicare & Medicaid Services (CMS) got into the act as well and included good pain control as one of the measures required for the recertification of hospitals. In January 2018, however, the three survey questions about pain management were replaced by three questions about communication about pain. In October of 2019, even these three items about communication about pain were completely removed from the CMS’ HCAHPS Survey. So hospitals and doctors no longer need to worry about relieving pain and the suffering that goes with it. Doctors have to worry more about losing their license or even being put into jail. I’ve testified in front of a disciplinary panel on behalf of a doctor who was at risk of losing his license. An adult patient’s mother complained to the state health department about her son getting prescriptions for opioid drugs. In this case, the doctor was exonerated but the financial and the emotional toll will certainly make him very unlikely to continue prescribing opioids drugs.

These drugs, despite their potential for causing addiction and other side effects, are life-savers for many people. When used judiciously and as part of a multidisciplinary approach, they can provide not only improved quality of life but can make a difference between disability and normal functioning.

A study just published in the journal Pain looked at the difficulties patients taking opioid drugs have in finding a primary care doctor.

This study examined if primary care clinics “are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioid use”. They conducted an audit survey of primary care clinics in 9 states from May to July 2019. They had simulated patients call the clinics and give one of two scenarios for needing a new provider: their previous physician had either (1) retired or (2) stopped prescribing opioids for unspecified reasons. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing.

The authors concluded that “…primary care access is limited for patients taking opioids for chronic pain.” and that “This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.”

Hopefully, the pendulum will soon begin moving closer to the middle. Another hope is that the researchers will finally discover the holy grail of pain management – a non-addictive pain medicine with few other side effects.

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Almost 1.5 million Americans visit emergency rooms every year for the treatment of head trauma. Headache, not surprisingly, is one of the most common symptoms of head trauma. What is very surprising is that until now, there have been no controlled studies of acute therapies for posttraumatic headaches.

Dr. Benjamin Friedman and his colleagues at the Montefiore Hospital in the Bronx just published a “Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache” in the journal Neurology. Emergency rooms often use metoclopramide (Reglan) as the first-line drug for the treatment of migraines. Diphenhydramine (Benadryl) was added to reduce the chance of side effects from metoclopramide. These side effects of restlessness and involuntary movements can be very unpleasant.

The study involved 160 patients. Their pain severity was measured on a 0 to 10 verbal scale. Patients who received a placebo reported a mean improvement of 3.8, while those receiving two medications improved by 5.2 points. Side effects occurred in 43% of patients who received medications and 28% of patients who received placebo.

My recent post was devoted to a study that showed dramatic similarities between migraines and posttraumatic headaches. The outcome of Friedman’s study, therefore, is not unexpected.

The overall efficacy of metoclopramide is fairly modest. It provides only partial relief that often does not last. And some patients get no relief at all. It also causes unpleasant side effects.

It is puzzling why emergency room doctors are not using a migraine-specific drug, sumatriptan for both migraines and posttraumatic headaches. An injection of sumatriptan works well within an hour for 70% of migraine patients. It has significantly fewer side effects than metoclopramide. Vials of sumatriptan (but not autoinjectors) are relatively inexpensive.

As far as the use of sumatriptan for posttraumatic headaches, we have only a few anecdotal reports. One of the reports, however, describes seven patients who did not respond to other drugs and had very good relief of their posttraumatic headaches with sumatriptan.

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Post-traumatic headaches (PTH) are classified as a distinct category of headaches. There is growing evidence, however, that headaches that develop after a head injury are migraines.

A study just published in Cephalalgia by Dr. Ann Scher, her colleagues at the Uniformed Services University, and other researchers, showed that PTH and migraines are very similar. The only difference they found was that headaches occurring after a head injury tend to be more severe.

They studied 1,094 soldiers with headaches. 198 were classified as having PTH. These headaches were compared to those in the other soldiers. They looked for the presence of 12 migraine features: Unilateral location, photophobia, phonophobia, nausea, exacerbation of headache by routine physical activity, pulsatility, visual aura, sensory aura, pain level, continuous headache, allodynia (sensitivity to touch), and monthly headache days.

Soldiers with post-traumatic headache had a greater endorsement of all 12 headache features compared to the soldiers with non-concussive headaches. The authors concluded that post-traumatic headaches differ from non-concussive headaches only by severity and not by any other symptoms.

Another study published in 2020 by Dr. Håkan Ashina and his Danish colleagues showed similar results. They performed a detailed evaluation of 100 individuals with persistent PTH following a mild traumatic brain injury. They found that 90 of the 100 patients had migraines or migraines as well as tension-type headaches. The rest had only tension-type headaches.

These findings have important treatment implications. These patients should be treated like other patients with chronic migraine. Assigning these patients the diagnosis of chronic migraine allows them access to treatments such as Botox injections and CGRP drugs. Insurance companies will not pay for any of the expensive migraine therapies if a patient carries only the diagnosis of PTH.

Our experience and that of our colleagues suggest that Botox is indeed very effective for PTH.

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This blog has many posts about the role of magnesium in the prevention of migraines and clinical trials of magnesium. Another study was just published by Iranian doctors in The Journal of Headache and Pain.

Unfortunately, like other studies, this one has a major flaw. Magnesium was given to all migraine sufferers, whether they were deficient in magnesium or not. If you are not deficient, taking extra magnesium will not help. For those who are deficient, however, the effect can be dramatic.

Another problem with this and several previous studies is the use of poorly absorbed salts of magnesium. In this case, magnesium oxide.

Patients in this study were divided into three groups. One group was given valproate (200 mg twice a day), the second group, valproate with magnesium oxide (250 mg twice a day), and the third group, magnesium oxide alone (also 250 mg twice a day). There were 82, 70, and 70 patients in each group, respectively.

Patients in the two groups that included valproate did better than those in the group taking magnesium alone. The combination of valproate with magnesium was more effective than valproate alone.

Surprisingly, the authors mention nothing about side effects. Valproate is one of the last drugs I use in migraine patients. It has many potential side effects, including weight gain, hair loss, tremor, nausea, and others. The majority of migraine sufferers are women of childbearing age and up to half of the pregnancies in the US are unplanned. So, another major reason I rarely prescribe this drug is that valproate is contraindicated in pregnancy. It can cause congenital malformations and developmental problems.

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Weight loss in overweight migraine sufferers – including that produced by bariatric surgery – leads to a reduction in the frequency of migraine attacks. In a previous post and in my new book I mentioned the use of metformin, a diabetes drug that helps weight loss, in migraine patients.

A study published in the February 10 issue of The New England Journal of Medicine definitively confirmed that weekly injections of another diabetes drug, semaglutide (Ozempic) can lead to an average of 15% weight loss in obese individuals. Seventy percent of participants lost at least 10% of weight. This was a double-blind, placebo-controlled trial that included 1,961 participants. Individuals in both the placebo and the active group were counseled every four weeks to encourage maintenance of a reduced calory diet and increased physical activity. Semaglutide is very similar to dulaglutide (Trulicity).

Other drugs that are used for weight loss produce an average of 4% to 6% weight loss and tend to have more side effects. Nausea and diarrhea were the most common adverse events with semaglutide. They were typically transient and mild-to-moderate in severity and subsided with time. Only 4.5% of participants on semaglutide stopped taking the drug due to side effects.

Obesity is a risk factor not only for diabetes and increased frequency of migraines but also strokes, idiopathic intracranial hypertension (pseudotumor cerebri), obstructive sleep apnea, hypertension, and others.

This trial should lead to the FDA approval of semaglutide for weight loss in obese individuals without diabetes. Hopefully, the FDA approval will compel insurance companies to pay for it. The out-of-pocket cost of 4 pen-like syringes is $735.

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The term postural orthostatic tachycardia means that the heart rate becomes very fast upon standing up. POTS is a disorder of the autonomic nervous system that is associated with abnormal blood flow regulation. Almost all patients with POTS suffer from migraines. POTS can present with a bewildering variety of additional symptoms besides headaches (see below). This is why the diagnosis is often missed. Unfortunately, there are very few effective treatments for POTS. Making the correct diagnosis, nevertheless, is very important. It explains the cause of symptoms that are often dismissed as psychological and in some patients, treatment can lead to a dramatic improvement.

This blog was prompted by a positive study of a drug, ivabradine, to treat POTS that was published by Dr. Pam Taub and her colleagues. Ivabradine (Corlanor) is approved by the FDA to treat heart failure, so its use for POTS is “off-label”. This means that insurance companies are not likely to cover an unapproved use of a drug that costs $500 a month. With additional trials confirming that ivabradine works and with a lot of persuasion by the doctor, insurers might cover it if other treatments fail. Currently, the drugs that are used to treat POTS include beta-blockers, midodrine, fludrocortisone, and others. Increased intake of salt and fluids, exercise, dietary changes, and correction of nutritional deficiencies such as vitamin B12 and magnesium cal also help.

Here is how the Cleveland Clinic website describes POTS:
POTS symptoms can be uncomfortable and frightening experiences. Patients with POTS usually suffer from two or more of the many symptoms listed below. Not all patients with POTS have all these symptoms.
High blood pressure/low blood pressure.
High/low heart rate; racing heart rate.
Chest pain.
Dizziness/lightheadedness especially in standing up, prolonged standing in one position, or long walks.
Fainting or near-fainting.
Exhaustion/fatigue.
Abdominal pain and bloating, nausea.
Temperature deregulation (hot or cold).
Nervous, jittery feeling.
Forgetfulness and trouble focusing (brain fog).
Blurred vision.
Headaches and body pain/aches (may feel flu-like); neck pain.
Insomnia and frequent awakenings from sleep, chest pain and racing heart rate during sleep, excessive sweating.
Shakiness/tremors especially with adrenaline surges.
Discoloration of feet and hands.
Exercise intolerance.
Excessive or lack of sweating.
Diarrhea and/or constipation.

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