Migraine | Headache NewsBlog

Migraine comorbidities

By: Dr. Mauskop

05-01-2020

If you suffer from migraines you are at a higher risk of having certain other medical problems, or comorbidities. They are not the result of having migraines, nor do those condition cause migraines. Most likely, they may have common underlying genetic, environmental, or behavioral factors. You should be aware of this link because treatment choice may be affected by the presence of these comorbidities.

Here is the list of conditions more common in migraines: anxiety, asthma, bipolar disorder, chronic pain, depression, fibromyalgia, reflux (GERD, or heartburn), irritable bowel syndrome (IBS), high cholesterol, hypertension, obesity, sleep apnea, TMJ syndrome. Having these coexisting diseases increases the risk of worsening (chronification) of migraines.

Migraine often coexists with another one or more painful conditions listed above – chronic pain (low back and other), fibromyalgia, irritable bowel syndrome, and TMJ. One plausible explanation is that chronic pain of one type leads to an increased sensitivity of brain cells. This increased sensitivity is well documented and is called wind-up phenomenon. Fortunately, many treatments can address several pain syndromes at once. These include antidepressant drugs (amitriptyline, duloxetine, and other), cognitive-behavioral therapy, exercise, and other.

One possible explanation for the coexistence of psychiatric disorders is that 40-60% of people with chronic pain have a history of physical, emotional, or sexual abuse and may suffer from posttraumatic stress disorder (PTSD). Another cause could be that they share serotonin and other neurochemical disturbances in the brain. Here too, antidepressants or certain epilepsy drugs may address both migraines and mood disorders.

Reflux (GERD) often seen in migraine sufferers could be the result of taking too many anti-inflammatory drugs such as ibuprofen, aspirin, and naproxen. Many patients will treat their heartburn with drugs such as omeprazole (Prilosec), which after prolonged use can cause multiple vitamin deficiencies, which in turn can worsen migraines and cause other symptoms.

Migraine has an inflammatory component and obesity is known to be pro-inflammatory, which could explain this connection. Diabetes drug, metformin could be a useful drug for patients who have difficulty losing weight with diet and exercise alone.

100 Migraine Drugs, A to Z: mirtazapine

By: Dr. Mauskop

30-12-2019

Migraine, Uncategorized

Mirtazapine (Remeron) is a tetracyclic antidepressant similar to tricyclic antidepressants and like tricyclics may have pain-relieving properties. The three and four cycles refer to the chemical formulas of these drugs, which contain 3 or 4 rings.

Mirtazapine tends to have fewer side effects than the tricyclic antidepressants, but its analgesic properties are much less proven than those of tricyclics. Only anecdotal reports suggest that it is effective in the preventive treatment of migraine headaches. In a small but well-conducted double-blind trial it was shown to provide good relief of tension-type headaches and a single case report described a patient whose cluster headaches consistently responded to mirtazapine.

Although it does have fewer side effects than tricyclics such as amitriptyline (Elavil) or nortriptyline (Pamelor), it still can cause somnolence and that is why it is taken at night. In patients with insomnia this can be a beneficial side effect. Similarly, it can also cause dizziness, weight gain, constipation, and dry mouth.

Mirtazapine has a narrower dose range (15 to 45 mg a day), which often means that it can be effective for depression as well pain. Tricyclics, on the other hand, often help pain at doses that are insufficient for the relief of depression. The average dose of amitriptyline and nortriptyline for the prevention of migraines and for the treatment of pain is between 25 and 75 mg, while for depression the dose goes up to 150 mg. One exception in the family of tricyclics is protriptyline (Vivactil), which is dosed at 10, 20 or 30 mg daily.

Ubrogepant (Ubrelvy), a new type of drug to treat acute migraines is approved by the FDA

By: Dr. Mauskop

23-12-2019

Headache medications, Migraine

Ubrogepant (Ubrelvy) is the first oral anti-CGRP drug to be approved by the FDA for the acute treatment of migraine attacks. It was developed by Allergan, manufacturer of Botox, the safest and arguably the most effective preventive treatment for chronic migraines. Allergan took a risk and bought this drug from Merck after Merck ran into problems developing a similar drug, telcagepant. Fortunately, ubrogepant had none of telcagepant’s problems and it was shown to be safe and effective in two large double-blind placebo-controlled trials.

The FDA-approved package insert says that, UBRELVY is a calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. The recommended dose is 50 mg or 100 mg taken as needed. If needed, a second dose may be administered at least 2 hours after the initial dose. The maximum dose in a 24-hour period is 200 mg. It can be taken with or without food. The most common side effects were nausea, seen in 2% of those receiving placebo, 2% of those on 50 mg of ubrogepant and 3% of patients taking 100 mg. The second most common side effect was somnolence, present in 1% of patients taking placebo, 2% of those taking 50 mg and 3% taking 100 mg.

Such a low incidence of side effects is extremely rare with oral drugs, but we also see this with injectable anti-CGRP drugs that are used for the prevention of migraines. The second oral anti-CGRP drug, rimegepant which is awaiting FDA approval, also seems to have very low rates of side effects, which is very reassuring.

The average cost of developing a new drug is $2.6 billion, which means that by necessity new drugs are expensive. This means that insurance companies will require that migraine patients first try and fail generic versions of triptans, such as sumatriptan (Imitrex) or have a contraindication to taking a triptan. Contraindications for the use of triptans include cardiovascular disease (coronary artery disease, strokes, heart attacks, etc.), uncontrolled hypertension, and a few other. Fortunately, ubrogepant can be safely used in such patients.

Oral triptans work well in about 60% of patients, which leaves millions of migraine sufferers without an effective abortive therapy and for these patients, the introduction of ubrogepant could be life-changing.

100 Migraine Drugs, A to Z: milnacipran

By: Dr. Mauskop

21-12-2019

Chronic migraine, Headache medications, Migraine

Milnacipran (Savella) is a drug that is approved by the FDA for the treatment of fibromyalgia. Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas.

Milnacipran belongs to the category of selective serotonin and norepinephrine reuptake inhibitors (SNRIs), which are used to treat anxiety, depression, and pain. There are four other SNRIs that are approved for the treatment of anxiety and depression, and in case of duloxetine (Cymbalta) also for fibromyalgia, peripheral nerve damage due to diabetes and musculoskeletal pain.

The manufacturer of milnacipran decided not to seek approval for the treatment of depression to avoid the stigma of being an antidepressant drug. Many patients feel that if they are prescribed an antidepressant, their pain is not perceived as real physical pain, but rather purely psychological.

Milnacipran was tested for the preventive treatment of migraines only in one unblinded observational study. Not surprisingly, it was effective. We often use duloxetine and venlafaxine (Effexor) for the treatment of migraines. Fibromyalgia, back pain, and other pains are comorbid with migraines, meaning that if you have one condition, you are more likely to have the other as well. Such patients are ideal candidates for SNRIs, although tricyclic antidepressants such as amitriptyline also work well for any pain and migraines.

Just like with other SNRIs, the most common side effects include nausea, headache, constipation, dizziness, insomnia, hot flushes, hyperhidrosis (excessive sweating), vomiting, palpitations, increased heart rate, dry mouth, and hypertension. Another common problem with these drugs is that many patients develop very unpleasant withdrawal symptoms if the drug is stopped abruptly.

Theoretically, antidepressants when used with triptans, such as sumatriptan can cause serotonin syndrome, but it is extremely rare and millions of people take both without any problems.

100 Migraine Drugs, A to Z: metoprolol

By: Dr. Mauskop

15-12-2019

Headache medications, Migraine

Metoprolol (Toprol) is one of the beta-blockers, drugs used for the treatment of hypertension and other heart conditions. It is one of the three beta-blockers (the other two are propranolol and timolol) that are included in the American Academy of Neurology guidelines for the preventive treatment of migraines.

A large double-blind study showed that metoprolol (200 mg/day) was more effective than aspirin (300 mg/day) in achieving 50% migraine frequency reduction (45% vs 30%). No significant side effects were reported in either group.

A small study reported that metoprolol (50–150 mg/day) had similar efficacy to nebivolol (another beta-blocker), 5 mg/day in reducing migraine attacks.

Metoprolol, unlike propranolol and timolol, is a selective beta-blocker, which means that it has a much lower chance of triggering an asthma attack in those who suffer from asthma or prone to occasional asthma attacks.

Some of the side effects that can occur with all beta blockers, including metoprolol, are tiredness., dizziness, constipation, blurred vision, chest pain, slowing of the heart rate, which can interfere with aerobic exercise, and other. Migraines are most common in young women many of whom have low blood pressure, which makes them more likely to develop dizziness and tiredness. It can also interfere with the best preventive treatment of migraines – regular exercise.

I reserve beta-blockers for those with normal or high blood pressure, those with rapid heart beat, and anxiety. It helps physical but not mental manifestations of anxiety – sweating, shaky voice, and fast heart rate. Beta-blockers are proven to help and are often taken in small doses for performance anxiety before giving a speech, presentation, or musical performance.

Triptans are woefully underutilized

By: Dr. Mauskop

08-12-2019

Chronic migraine, Headache medications, Migraine

When sumatriptan (Imitrex) was introduced in 1992 it was truly a breakthrough drug – the first drug specifically developed for the acute treatment of migraines. Sumatriptan and six other triptans have alleviated suffering of millions of people. Sumatriptan is considered to be the gold standard therapy for an acute migraine. Unfortunately, 27 years later many millions of migraine sufferers have not had a chance to try these drugs.

A study by R. Lipton and his colleagues presented earlier this year surveyed 15,133 migraine sufferers. Only 37% had ever used a triptan and only 16% were using them at the time of the survey. Most patients used tablets, but 11% also tried either a nasal spray or an injection. Lack of efficacy (in 38%) and side effects (in 22%) were the most common reason for stopping the drug and the most common side effects were dizziness, nausea, and fatigue.

My guess is that lack of efficacy is often due to the suboptimal dose of a triptan that is often prescribed. I see many patients who tell me that they’ve tried sumatriptan and it did not work, but many of them took 25 or 50 mg, while an effective dose for most patients is 100 mg. Most other triptans are also available in two different strengths and the lower, less effective dose is often prescribed.

Another common problem is that patients who fail one triptan due to side effects or lack of efficacy are not prescribed a different triptan. Many of my patients find that one triptan is more effective than another or if one triptan causes side effects, a different one may not. Also, if a tablet does not work, an injection or a nasal spray might, especially in patients with a quick buildup of pain or when nausea is present.

A big reason for the underutilization of triptans is misdiagnosis of headaches. Almost half of migraine sufferers are told that they have sinus or tension headaches, which means they are missing out on receiving effective treatment.

Safety of triptans is a concern of many physicians and patients. The package insert warns about strokes and heart attacks and it is true that if you have untreated hypertension, coronary artery disease or many risk factors for coronary artery disease it is better to avoid triptans. However, triptans have been available without a prescription for over 10 years in most European countries.

A panel of leading headache specialists published a “Consensus Statement: Cardiovascular Safety Profile of Triptans in the Acute Treatment of Migraine” that states “The incidence of serious cardiovascular events with triptans in both clinical trials and clinical practice appears to be extremely low “.

Another unfounded concern of many physicians is that frequent use of triptans will make migraines more frequent and severe. There is no good scientific evidence for this concern. You can read my two previous blog posts on this topic here and here. The first of these two posts is by far the most popular on this site with over 300 comments. Many patients report how relieved they are to hear that they are not risking their lives by taking triptans often or even daily and also how frustrated they are not being able to find a doctor who would prescribe a sufficient amount of this medicine.

Sumatriptan was first released in a pack of 9 tablets, but not because it was dangerous to take more, but mostly because this was the average number of tablets people used in one month in clinical trials. Cost used to be another limiting factor and some insurers still limit triptans to 6 or 9 tablets a month. However, generic sumatriptan now can be found for as little as $12-20, so patients can bypass their insurance and buy as many additional tablets as they might need.

100 Migraine Drugs, A to Z: methylergonovine

By: Dr. Mauskop

29-11-2019

Headache medications, Migraine

Methylergonovine (Methergine) is used intravenously or in a tablet form after childbirth to help stop bleeding from the uterus. Methylergonovine belongs to the class of drugs known as ergot alkaloids. A drug in this class that is in wide use for the treatment of migraines is dihydroergotamine (DHE). DHE is one of the most effective drugs for the treatment of an acute migraine when given by injection.

Methysergide (Sansert) was another drug in this class and in a tablet form was used for the prevention of migraine and cluster headaches. It was very effective, but because of a very rare but serious side effect was withdrawn from the market. This was unfortunate because a small group of patients for whom other drugs were ineffective were glad to take that risk in exchange for significantly improved quality of life.

After the withdrawal of methysergide, the only oral ergot drug left on the market was methylergonovine and headache specialists continue to use it for their difficult to treat migraine and cluster patients. Methylergonovine was first reported to be effective for the treatment of migraines with medication overuse in an open-label trial of 60 patients in 1993. Of these 60 patients, 44 or 73% improved.

Another uncontrolled trial of methylergonovine in 20 cluster headache patients also showed it to be very effective. Intravenous infusion of this drug given to 125 migraine patients presenting to the emergency room provided pain freedom after one hour in 74%. This was also an uncontrolled, open-label study, which means that placebo effect very likely played a role.

This being an ergot alkaloid, we have to assume that its prolonged use also has the potential to cause serious side effects similar to methysergide. This side effect is fibrosis, or the development of scarring around kidneys, heart, or lungs. Even though it is very rare, this is a greatly feared side effect because it has no treatment and can lead to loss of function in kidneys, heart or lungs. It is speculated, but not proven, that stopping the drug for a month after 3 or 6 months of continuous use may prevent this side effect.

Vitamin B12 and migraines

By: Dr. Mauskop

24-11-2019

Alternative Therapies, Migraine

Vitamin B12 (cyanocobalamin) deficiency has been long suspected to play a role in the development of migraines, but so far it has not been directly linked to migraines.

A new study published in the latest issue of Headache compared vitamin B12 status in 70 migraine sufferers with 70 healthy people with similar demographics. Serum levels of vitamin B12 were found to be significantly lower in migraine patients than in healthy subjects. Vitamin B12 levels are notoriously inaccurate, so the authors confirmed this finding by testing for a more sensitive indicator of deficiency, methylmalonic acid (MMA), which goes up as the vitamin B12 levels go down. Patients with the B12 levels in the highest quartile had 80% lower chance of having migraines compared to those with levels in the bottom quartile. Patients in the highest quartile of MMA had more than 5 times increased risk of having migraines.

In a study migraine sufferers with elevated homocysteine levels, which is another indicator of deficiency of vitamin B12 and other B vitamins, were given vitamins B12, folic acid and vitamin B6. Their homocysteine levels dropped and migraine-related disability improved. Elevated homocysteine level is suspected to be responsible for the increased risk of strokes in patients with migraines with aura, although that is still unproven.

This latest study only shows correlation, but it does not prove that taking vitamin B12 and increasing your serum level will relieve migraines. Nevertheless, it makes sense to have your level at least in the middle of normal range since vitamin B12 is important for many brain functions. For example, multiple sclerosis patients with low B12 levels have higher disability and vitamin B12 deficiency may predispose to Alzheimer’s disease.

I’ve written in the past that long-term intake of heartburn drugs often leads to vitamin B12 deficiency. You may want to read an article in the Wall Street Journal published earlier this year, Vitamin B-12 Deficiency: The Serious Health Problem That’s Easy To Miss.

100 MIgraine Drugs, A to Z: metformin

By: Dr. Mauskop

16-11-2019

Headache medications, Migraine

Metformin (Glucophage, Glumetza) is a drug for the treatment of diabetes and you will not find any scientific articles if you google “metformin and migraine”. However, I’ve been prescribing metformin to some of my migraine patients with some success. In the absence of controlled trials to prove its efficacy, one can argue that those patients who improved are experiencing the placebo effect. However, there are two possible ways by which metformin can help prevent migraines.

Obesity does not predispose one to migraines, but in those who do suffer from migraines increased weight is associated with an increased frequency and severity of migraine attacks. Since metformin is proven to help reduce weight, this could be one of the mechanisms by which it improves migraines. Weight loss due to metformin has been shown to be sustainable for up to 10 years.

The second possible mechanism is metformin’s direct effect on inflammation, which is one of the major mechanisms involved in migraines.

I usually prescribe metformin to patients who are overweight and I prefer metformin to the most popular migraine preventive drug, topiramate (Topamax). Topiramate can cause difficulty with memory, kidney stones, osteoporosis, acute glaucoma and other serious side effects, while metformin only occasionally causes nausea. If nausea does occur, changing to a slow release form of metformin (metformin ER) usually helps. Metformin can also cause a drop in vitamin B12 level, so it is worth prescribing a vitamin B12 supplement along with metformin. Metformin should not be prescribed to patients with impaired kidney function, so a baseline blood test is necessary.

Another group of patients I prescribe metformin to are those who are not obese, but report having migraines due to low blood sugar – either when they are hungry or after eating carbohydrate-rich foods, which can lead to a drop in blood glucose (so called reactive hypoglycemia). They often report feeling less hungry and not needing to eat frequently to avoid migraines. Metformin works by regulating the release of glucose from the liver to maintain a steady level of glucose in the blood. This is why this drug does not cause a drop in blood glucose level like other diabetes medications and can be taken by non-diabetics.

The starting dose of metformin is 500 mg a day and if necessary, it can be increased to 1,000 and up to 2,000 mg a day.

Metformin has another unproven potential benefit – it may make you live longer. For now, it’s been shown to be the case only in mice, fruit flies and worms.

100 Migraine Drugs, A to Z: clopidogrel

By: Dr. Mauskop

10-11-2019

Headache medications, Headaches, Migraine

Clopidogrel (Plavix) was not on my original list of 100 migraine drugs, but I decided to add it after another mention of this drug at the last congress of the International Headache Society in Dublin (since I keep adding drugs and new ones are being released, the list will exceed 100).

Patients who suffer from migraines, especially those who have auras, have a higher incidence of a persistent opening between the left and the right side of their heart, called patent foramen ovale or PFO. PFO is found in 25% of the general population, is usually small and causes no symptoms. When it is large, it needs to be closed, which can be done through a vein in the groin. Unfortunately, studies that aimed to relieve migraines by closing the PFO did not show much benefit. However, blood thinners used after the procedure may have helped some patients.

I first mentioned clopidogrel in a blog post from 2007 when describing a British doctor’s experience with a few of his patients. In another blog post from 2015 I mentioned a study that showed that clopidogrel with aspirin was more effective in improving migraines than aspirin alone. A study comparing aspirin and clopidogrel showed them to be equally effective in improving migraines in patients with a PFO.

In the study presented in Dublin by two Chinese doctors PFO was found in 151 out of 266 (57%) of all migraine patients, of whom 65 the opening was large. PFO was found in 59 out of 84 (70%) of all migraine with aura and 36 patients had a large opening. 27 migraine patients who did not respond to standard medical therapy were given clopidogrel, 75 mg a day for 3 months. 22 patients completed this study. Headache frequency, severity and duration were significantly decreased by addition of this drug. Migraine-related disability was also reduced.

Aspirin, clopidogrel as well as prasugrel (Effient) and ticagrelor (Brilinta) are drugs that inhibit the function of platelets, small blood particles that are involved in blood clotting. Platelet dysfunction and other blood clotting problems have been suspected to play a role in triggering migraines, but the scientific evidence has been lacking.

A report by a cardiologist Dr. Robert Sommer and his colleagues at the Columbia University Medical Center suggests that platelets do contribute to migraines in some patients. They reviewed records of their 136 patients (86% female, mean age 38 years, with an average of 15 headache days a month). Migraines improved on clopidogrel in 80 (59%). The clopidogrel was equally beneficial in patients with episodic and chronic migraines, with and without aura. When the researchers tested platelets in non-responders, 19 of 45 (40%) did not have their platelets inhibited by clopidogrel. Sixteen of those patients were switched to prasugrel, which adequately inhibited platelets and 10 of 16 (62%) had improvement in their migraines. 56 of 90 responders had their PFO closed and the drug stopped after 3 months, which is typically done after a PFO closure. Ninety-four percent had ongoing migraine relief. All 8 of 8 responders who stopped their medication without PFO closure had worsening of their migraines.

This was not a blinded study, so it is premature to recommend PFO closure to migraine patients. However, it can be argued that patients whose migraines do not respond to several drugs, Botox, and monoclonal antibodies should have an echocardiogram to look for a PFO and if one is found, at least given a trial of an antiplatelet medication.

100 Migraine Drugs, A to Z: memantine

By: Dr. Mauskop

04-11-2019

Chronic migraine, Headache medications, Migraine

Memantine (Namenda) is an Alzheimer’s drug that has been used for the treatment of pain and migraine headaches. This drug blocks the NMDA receptor in the brain, which is involved in the processing of pain messages and in other neurological conditions such as epilepsy, stroke and traumatic brain injuries.

NMDA receptor antagonist dizocilpine, or MK801 was a drug with a potential to treat all these conditions, but unfortunately it had serious side effects and after spending hundreds of millions of dollars, Merck stopped its development. It is possible that strong inhibition of the NMDA receptor will always lead to serious side effects. We do have several other milder NMDA inhibitors, besides memantine – dextromethorphan, which is used as a cough suppressant and ketamine.

Memantine, 10 to 20 mg a day was studied in 28 patients with migraines that were not responding to at least two standard medications and was found to be effective. A double-blind, placebo-controlled trial of 10 mg of memantine in 52 patients was also positive. Another double-blind placebo-controlled trial of 60 patients also showed some benefit. A review of case reports and two controlled studies concluded that memantine, 10 to 20 mg a day may be an effective treatment for the prevention of migraines. A study of 40 mg of memantine for chronic tension-type headaches did not show any efficacy, although women seemed to benefit more than men. The only side effects of this relatively high dose (the Alzheimer’s dose is 20 mg) were nausea and dizziness. Overall, memantine tends to be well tolerated, even in the elderly with Alzheimer’s.

I do occasionally prescribe memantine and tend to increase the dose to 20 mg twice a day. I have only a few patients who obtained very good relief and remain on the drug. It is certainly not the first, second, or third drug I prescribe, but when many other drugs fail, it is worth a try since potential side effects are relatively mild.

Cove, a telemedicine startup for migraine sufferers

By: Dr. Mauskop

30-10-2019

Alternative Therapies, Headache medications, Headaches, Migraine, New treatments

Cove, a telemedicine startup provides medical care to people suffering from migraines. There are 40 million migraine sufferers in the US, only half of whom seek medical care. The other half may have mild migraines, not have access to medical care, or are under the impression that nothing can be done about their headaches. Only half of the half that go to a doctor receive a correct diagnosis of migraine. The other half, or about 10 million, are misdiagnosed as sinus, tension, or stress headaches and never receive effective treatment.

Withcove.com is website where migraine sufferers can have a neurologist evaluate their symptoms and provide an accurate diagnosis and prescribe individualized treatment. It may seem that not seeing a doctor in person would be a major obstacle, but it is not. The patient completes a questionnaire and video is used for neurological examination. The doctor evaluates the information and prescribes migraine drugs, both for the acute treatment of an attack, as well for prevention. You don’t even need to go to a pharmacy – the medicine is shipped to you. Cove also offers a variety of supplements, such as magnesium and CoQ10, which can be more effective and safer for the prevention of migraines than drugs.

My colleague at the NY Headache Center, Dr. Sara Crystal and I are helping Cove with the design of proper evaluation tools, treatment algorithms, and other aspects of care.

In addition to providing direct care, Cove is conducting some research as well. In a survey of nearly 1,000 people, a combination of Cove customers and other migraine sufferers, Cove looked at the impact of migraine on careers, to identify coping strategies, and to provide tools that make it easier to get ahead. You can read the full report, “When Migraine Gets In the Way of Careers”.

Here is a sample of the survey findings:
47% of migraine sufferers who are employed feel that migraines have held them back from advancing in their career.
30% of employed migraine sufferers said that they’ve needed to quit a job, turn down responsibilities at their current job, and/or not accept a new job because of their migraines.
38% of employed migraine sufferers have missed 5+ days of work in the past 12 months due to their migraines.

These are shocking numbers, but in line with the data known to headache specialists. Migraine is ranked globally as the seventh most disabling disease among all diseases and is the leading cause of disability among all neurological disorders. Unfortunately, research into migraines does not receive appropriate attention from the National Institutes of Health and other funding sources.