Headache NewsBlog

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.

100 Migraine Drugs, A to Z: meloxicam

By: Dr. Mauskop

28-10-2019

Headache medications, Migraine

Meloxicam (Mobic) is a non-steroidal anti-inflammatory drug (NSAID) which is approved for the treatment of rheumatoid arthritis and osteoarthritis in adults and juvenile rheumatoid arthritis in children older than 2 years. Meloxicam tends to be better tolerated than some other NSAIDs. The main side effects of NSAIDs are heartburn (reflux), stomach pain, and peptic ulcers.

Although there have been no trials of meloxicam for the acute or prophylactic treatment of migraine headaches, it is probably as effective as other NSAID that have been tested for migraines. One advantage of meloxicam is that the effect of a single dose lasts all day. This makes it particularly suitable for the prevention of migraine attacks. It is also available in a liquid form, which can work faster than a solid tablet and speed of onset can be important when using it for acute therapy since faster acting drugs tend to be more effective. Meloxicam tablets are available in 7.5 and 15 mg strength.

An abstract presented at the recent meeting of the International Headache Society describes a new combination product in development for the acute treatment of migraines, which includes meloxicam, 20 mg with rizatriptan (Maxalt), 10 mg. This is a product similar to the combination of naproxen with sumatriptan (Treximet) and just like Treximet is likely to be more effective than either drug alone. However, being a branded drug it is likely to be much more expensive than generic drugs and not likely to be covered by most insurance plans. The insurers usually require that a patient first tries taking sumatriptan and naproxen as separate tablets and if that does not work, will occasionally pay for Treximet. I do have a small number of patients who respond much better to Treximet than to sumatriptan and naproxen taken as separate pills. This can be due to several factors. Most commonly, certain generics may not dissolve as fast as the branded product. Another possible explanation is that the acidity of NSAIDs such as naproxen or meloxicam facilitates absorption of triptans, which could be more pronounced if they are in close contact.

Thinking fast and slow when prescribing opioids

By: Dr. Mauskop

20-10-2019

Brain disorders, Headache medications, Pain, Pain Research

It is not surprising that when a doctor is tired or hurried he or she is more likely to make a mistake. A new study published in JAMA Network Open provides some hard data on doctor performance as it relates to the prescribing of opioid (narcotic) analgesics. Opioids are still overprescribed, especially for migraine headache patients.

The researchers at the University of Minnesota discovered that doctors were 33% more likely to prescribe an opioid pain medicine at the end of the workday than in the beginning. If the doctor was running an hour or more behind schedule her or she was 17% more likely to prescribe an opioid. Prescribing of nonsteroidal anti-inflammatory drugs and referral to physical therapy did not display similar patterns. This was a very large study which means that the results are likely to be reliable. The study looked at 5,603 primary care practitioners who were involved in 678,319 primary care encounters for a painful condition.

Prescribing an opioid seems like a quick fix for a problem that saves doctors time, but usually is not be the best treatment for the patient.

Nobel Prize winner Daniel Kahneman in his book, Thinking Fast and Slow suggests that there are additional and easily correctable factors that may be contributing to poor decision making. Here are some quotes from the book.

“The most surprising discovery made by Baumeister’s group shows, as he puts it, that the idea of mental energy is more than a mere metaphor. The nervous system consumes more glucose than most other parts of the body, and effortful mental activity appears to be especially expensive in the currency of glucose. When you are actively involved in difficult cognitive reasoning or engaged in a task that requires self-control, your blood glucose level drops.

The bold implication of this idea is that the effects of ego depletion could be undone by ingesting glucose, and Baumeister and his colleagues have confirmed this hypothesis in several experiments… Restoring the level of available sugar in the brain had prevented the deterioration of performance.

A disturbing demonstration of depletion effects in judgment was recently reported in the Proceedings of the National Academy of Sciences. The unwitting participants in the study were eight parole judges in Israel. They spend entire days reviewing applications for parole. The cases are presented in random order, and the judges spend little time on each one, an average of 6 minutes. (The default decision is denial of parole; only 35% of requests are approved. The exact time of each decision is recorded, and the times of the judges’ three food breaks—morning break, lunch, and afternoon break—during the day are recorded as well.) The authors of the study plotted the proportion of approved requests against the time since the last food break. The proportion spikes after each meal, when about 65% of requests are granted. During the two hours or so until the judges’ next feeding, the approval rate drops steadily, to about zero just before the meal. As you might expect, this is an unwelcome result and the authors carefully checked many alternative explanations. The best possible account of the data provides bad news: tired and hungry judges tend to fall back on the easier default position of denying requests for parole. Both fatigue and hunger probably play a role.”

So for best results you may want to try to see your doctor right after lunch and hope that he or she had time to eat lunch.

More evidence that Botox relieves not only migraines, but also depression

By: Dr. Mauskop

14-10-2019

Alternative Therapies, Botox, Brain disorders, Chronic migraine, Migraine

A large study confirms previous reports of the beneficial effect of onabotulinumtoxinA (Botox) injections on depression as well as anxiety. In my two previous blog posts from 2011 and 2014 I mentioned reports of cosmetic Botox injections relieving depression but those involved a relatively small number of patients.

A study published in the Journal of Neurology, Neurosurgery, & Psychiatry under the title Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety ,described the COMPEL trial (Chronic Migraine OnabotulinumtoxinA Prolonged Efficacy Open-Label). It was a multicenter, open-label, prospective study assessing the long-term safety and efficacy of 155 units of onabotulinumtoxinA (Botox) over nine treatments (108 weeks) in adults with chronic migraines.

OnabotulinumtoxinA treatment was associated with sustained reduction in headache days and depression and anxiety scores in the 715 patients over 108 weeks. The anxiety and depression scores were significantly reduced at all time points in patients with clinically significant symptoms of depression and/or anxiety at baseline. By week 108, 78% and 82% had clinically meaningful improvement in depression and anxiety symptoms, respectively. Sleep quality and symptoms of fatigue also improved.

In an earlier poster presentation of this data at a scientific conference the authors reported that the improvement in anxiety and depression was seen even in patients whose migraines did not improve with Botox. Even if that were true, we need a separate large study of Botox for anxiety and depression. The one study that treated patients with major depression in a double-blind, placebo-controlled trial involved only 74 patients.

In my practice, I’ve treated one young woman with severe bipolar disorder which did not respond to multiple drugs and who had a dramatic response to Botox. She has been receiving injections for over two years with sustained improvement. Another young man with depression had a very significant response as well, but has had only one treatment so far. I came to treat them accidentally – both were adopted children of my migraine patient who read about this possible effect of Botox and asked me to try it.

100 Migraine Drugs, A to Z: mefenamic acid

By: Dr. Mauskop

06-10-2019

Headache medications, Migraine

Mefenamic acid (Ponstel) is one the nonsteroidal antiinflammatory drugs (NSAIDs) and like all other NSAIDs it is being used for the treatment of acute migraine attacks.

Mefenamic acid is popular for the treatment of menstrual migraines, which probably stems from the fact that in addition to the treatment of mild or moderate pain, it is also approved for the treatment of dysmenorrhea, or pain of menstruation. In a small study mefenamic acid was found to be specifically effective for the treatment of menstrual migraines, which can be more severe and more difficult to treat than non-menstrual attacks.

Mefenamic acid was found to be superior to acetaminophen (called paracetamol in Europe), which is no surprise since acetaminophen has little antiinflammatory action and therefore does not reduce inflammation that occurs during a migraine attack.

Ergotamine was the mainstay of migraine treatment before the introduction of triptans in 1992. A study comparing ergotamine with mefenamic acid was found them to be equally effective, but ergotamine caused more side effects, especially nausea, which is a common side effect of ergot derivatives.

A small trial suggests that it can be also used for the prevention of migraines and it is as effective as propranolol.

For the treatment of pain and primary dysmenorrhea, the initial dose is 500 mg, followed by 250 mg every 6 hours, as needed. Just like other NSAIDs, it can cause heartburn, stomach upset, bleeding ulcers, and other side effects.

Caffeine and migraine headaches

By: Dr. Mauskop

01-10-2019

Alternative Therapies, Headaches, Migraine

Medication overuse headache (MOH) is not proven to occur from the frequent intake of triptans (Imitrex, or sumatriptan and other) or NSAIDs (ibuprofen, naproxen, and other). However, there is good evidence that caffeine (and opioid analgesics) which can help relieve an occasional migraine, can definitely make them worse if taken frequently. Caffeine withdrawal is a proven trigger of headaches, including migraines.

While we know that caffeine withdrawal causes headaches, a study just published by Harvard researchers in The American Journal of Medicine addressed an unexamined question – does drinking coffee directly triggers a migraine?

This was a rigorous prospective study of 98 adults with episodic migraine who completed electronic diaries every morning and evening for a minimum of 6 weeks. 86 participants were women and 12 were men, with mean age of 35 and the average age of onset of headaches of 16. Every day, participants reported caffeinated beverage intake, other lifestyle factors, and the timing and characteristics of each migraine headache. The researchers compared incidence of migraines on days with caffeinated beverage intake to the incidence of migraines by the same individual on days with no intake. In total, the participants reported 825 migraines during 4467 days of observation.

There was a significant association between the number of caffeinated beverages and the odds of migraine headache occurrence on that day. This association was stronger in those who normally drank 1-2 cups of coffee daily – they were more likely to get a migraine on days when they drank 3 or more cups.

Even after accounting for daily alcohol intake, stress, sleep, activity, and menstrual bleeding, 1-2 servings of caffeinated beverages were not associated with headaches on that day, but 3 or more servings were associated with higher odds of headaches, even after accounting for daily alcohol intake, stress, sleep, activity, and menstrual bleeding. The researchers also considered the possibility of reverse causation, meaning that people might have drank coffee to treat a headache, but this was also not the case.

My advice to migraine sufferers is to drink not more than 1 cup of coffee a day, and I don’t mean a Venti (24 oz) cup from Starbucks, but an 8-ounce cup of regular strength coffee. During a migraine attack having an extra cup along with your usual medication may provide additional relief.

100 Migraine Drugs, A to Z: lidocaine

By: Dr. Mauskop

23-09-2019

Headache medications, Migraine

Lidocaine (Xylocaine) is an old local anesthetic used by surgeons, dentists, and other doctors to numb parts of the body. Lidocaine drops given into the nostrils were compared to saline drops for the acute treatment of migraine attacks in a double-blind placebo-controlled 113-patient trial by Dr. Morris Meizels and his colleagues. This study showed that lidocaine nose drops were much more effective than saline drops, but relieved migraines in only about one third of patients. Another, but smaller (49 patients) study did not find a difference between lidocaine and saline.

I’ve had a handful of patients with difficult to control migraines respond to an intravenous infusion of lidocaine and one of these patients continues to do well with a monthly infusion of lidocaine. There have been no double-blind studies of intravenous lidocaine for migraines, but an observational study of 68 hospitalized patients who failed to respond to other treatments, suggests that this treatment can be effective for some patients.

Intravenous administration of lidocaine is usually done in a hospital or an outpatient facility that has cardiac monitoring because lidocaine can cause arrhythmias (irregular heart beat). Otherwise, lidocaine is safe and well tolerated.

The widest use of lidocaine in migraine is for nerve blocks. An occipital nerve block has been scientifically proven to relieve an acute migraine attack. Combining blocks of occipital nerves (in the back of the head) with a block of supraorbital nerves (in the forehead) has been also shown to be more effective than injections of saline. We often add blocks of the temporal branches of the trigeminal nerve (in the temples) when a patient has pain in those areas.

Nerve blocks sometimes help stop a persistent migraine when other treatments fail. It is also a very good option for pregnant women who cannot or would rather not take any medicine by mouth.

By: Dr. Mauskop

15-09-2019

Migraine

On September 12, 2019, Dr. Mauskop spoke on Advances and Controversies in Migraine at Charité – Universitätsmedizin Berlin, Europe’s largest university hospital. In the top photo Dr. Mauskop with Professor Uwe Reuter of Charité and Dr. Zoltan Medgyessy of Detmold Medicum. The middle photo shows the entrance to the renown Psychiatric and Neurologic Clinic at Charité. Bottom photo is of Dr. Mauskop in the lecture hall, where at the top you can see six portraits of physicians, who after 1933 were dismissed and persecuted for political or racial reasons.

Vitamin D and migraine

By: Dr. Mauskop

11-09-2019

Alternative Therapies, Migraine, Science of Migraine

At the biennial International Headache Congress held last week in Dublin a group of Italian researchers presented a paper, Relationship between severity of migraine and vitamin D deficiency: a case-control study.

They examined 3 groups of subjects: 116 patients with chronic migraine, 44 patients with episodic migraine, and 100 non-headache controls. Ninety-two migraine patients had vitamin D insufficiency (borderline low levels), whereas 40 had a clear vitamin D deficiency. They found a strong inverse correlation between vitamin D levels and the severity of attacks as well as migraine-related disability.

This is only a correlational study, meaning that it does not prove that taking vitamin D will help relieve migraines. However, several neurological disorders seem to be associated with low vitamin D levels, suggesting that vitamin D is very important for the normal functioning of the nervous system. So it makes sense to keep your vitamin D levels at least in the middle of normal range.

100 Migraine Drugs, A to Z: levetiracetam

By: Dr. Mauskop

03-09-2019

Headache medications, Migraine

Levetiracetam (Keppra) is an epilepsy drug that has been reported to help some patients with migraines. However, unlike divalproex sodium (Depakote) and topiramate (Topamax, Trokendi, Qudexy), the evidence for its efficacy in migraines is weak.

This evidence consists mostly of uncontrolled observational studies without a comparison to placebo. One small double-blind placebo-controlled study compared 500 mg of levetiracetam (27 patients) to 500 mg of divalproex sodium (32 patients) and to placebo (26 patients). Both epilepsy drugs were superior to placebo.

In one of the reports the mean dose of levetiracetam was 1,125 (and up to 2,000), while the maximum dose for epilepsy is 3,000). It is possible that the drug may work better at a higher dose. However, with an increase in the dose there is an increase in side effects. These include weakness, drowsiness, dizziness, anxiety, depression, irritability and aggressive behavior, and other.

Since this drug is not proven to be effective and can have serious side effects, I never prescribe this drug.