Headache NewsBlog

Migraine Associated With Dementia, Alzheimer’s in Women

By: Dr. Mauskop

26-08-2019

Alternative Therapies, Brain disorders, Migraine

An alarming study entitled Association Between Migraine Headaches and Dementia in More than 7,400 Patients Followed in General Practices in the United Kingdom was just published in the Journal of Alzheimer’s Disease. The researchers found that the risk for ALzheimer’s and other dementias is increased only in women with migraines and not in men.

The first large study to discover an association between migraines and dementia was done in Taiwan. Interestingly, a follow-up study in Taiwan discovered that people who used traditional Chinese medicine (mostly herbal products Jia-Wei-Xiao-Yao-San and Yan-Hu-Suo) had lower risk of dementia than those who did not.

There is no need to panic since other studies have found no such association and there is a wide range of preventive measures that are proven effective.

Controlling ones blood pressure, blood glucose, cholesterol level, and avoiding smoking are extremely important in lowering the risk of Alzheimer’s.

The single most effective preventive measure is regular physical exercise, which is more effective than mental exercise. Engaging in mental activities, such as learning languages, solving crossword puzzles, and playing bridge (which adds the benefit of social contacts) can also help. Dancing and tai chi combine physical and social benefits. Meditation appears to be effective in preventing shrinkage of the brain, which used to be thought a normal part of aging. This was confirmed in more than one study.

In addition to Chinese herbal products mentioned above, there are several other supplements that are also less proven but are safe and may help prevent Alzheimer’s. These include vitamins B12 and D, magnesium, curcurmin, nicotinamide, and possibly other.

100 Migraine Drugs, A to Z: ketorolac

By: Dr. Mauskop

19-08-2019

Headache medications, Migraine

Ketorolac (Toradol) is one of many nonsteroidal anti-inflammatory (NSAID) pain medications used to treat migraine headaches. In a tablet form it is no more effective than ibuprofen, naproxen or any other NSAID, but has more side effects and its use is limited to 5 days. On the other hand, ketorolac in an injection is a unique and very useful drug. It provides pain relief comparable to that of opioid (narcotic) drugs without the side effects or addiction potential of those drugs.

Intravenous ketorolac has been proven to be an effective drug for the treatment of severe migraine attacks. A study done by Dr. B. Friedman and his colleagues at the emergency department of the Montefiore Medical Center in the Bronx compared intravenous infusion of 30 mg of ketorolac with an infusion of 10 mg of metoclopramide (Reglan) and 1,000 mg of valproate (Depacon). There were over 100 patients in each group, making this a highly reliable study. Ketorolac and metoclopramide were more effective than valproate, but metoclopramide caused severe restlessness in 6 (6%) of patients. This is a well known side effect of metoclopramide and a similar drug, prochlorperazine (Compazine). This side effect is extremely unpleasant, but can be relieved by diphenhydramine (Benadryl).

Intramuscular injection of 60 mg of ketorolac was compared to intravenous infusion of 25 mg of chlorpromazine (Thorazine) and they were found to be equally effective. Just like prochlorperazine, chlorpromazine carries a risk of restlessness, as well as involuntary movements and sedation. These two drugs belong to the phenothiazine family of drugs, which are also used for severe nausea and vomiting, and psychiatric disorders.

A review of eight published trials of ketorolac found it to be more effective than meperidine (Demerol) and sumatriptan and a little less effective than metoclopramide, chlorpromazine and prochlorperazine. However, ketorolac lacks the addiction potential and the risk of severe restlessness, sedation, and involuntary movements.

We given intravenous ketorolac to our patients whose migraine has not responded to an injection of sumatriptan or oral triptans, although we almost always give an infusion of magnesium before or along with ketorolac.

Here is a blog post with my advice on what to ask for if your migraine lands you in an emergency room.

tDCS, which we are testing for migraines, may relieve depression

By: Dr. Mauskop

12-08-2019

Alternative Therapies, Chronic migraine, Migraine

Transcranial direct current stimulation (tDCS) has been definitively shown to alter brain connectivity and function. We are still enrolling patients in our double-blind study of tDCS for the prevention of migraines, so please contact us if you are interested.

A group of Iranian researchers used tDCS to treat “treatment-resistant major depression”. The results of this double-blind randomized sham-controlled trial were published in Clinical EEG and Neuroscience.

Patients with less than 50% decrease in the intensity of depression after 8 weeks of treatment with selective serotonin reuptake inhibitors (drugs like Prozac or fluoxetine, Lexapro or escitalopram, and other) were included in the trial. 16 women and 14 men were randomly allocated to an active group, which received 2-mA stimulation for 20 minutes per session, or the sham group. The Hamilton Depression Rating Scale was used to measure the severity of depression. There were statistically significant differences in the mean Hamilton scores in favor of the active treatment compared to the sham group. The difference in improvement persisted for a month after the treatment ended.

The authors’ conclusion that “tDCS is an efficient therapy for patients with resistant major depression, and the benefits would remain at least for 1 month” may be premature because of the small sample size. However, other studies have also indicated that tDCS may be effective in depression. Considering its low cost and very high safety, tDCS may be worth trying in patients with depression.

The same may apply to patients with migraines since several small studies have found this method effective. We hope that our larger study will confirm these findings. Our study differs from the previous ones and the ones for depression in that patients sue the device at home daily, rather than coming to the clinic to get the treatment. We hope that this difference will result in better outcomes.

Migraine does not increase the risk of strokes in postmenopausal women

By: Dr. Mauskop

10-08-2019

Brain disorders, Migraine

Migraine with and without aura carries an increased risk of strokes and heart attacks, according to several large studies. Most migraine sufferers are young women and until now there have been no studies looking at postmenopausal women.

At the last annual scientific meeting of the American Headache Society, Dr. Pavlovic and her colleagues at the Albert Einstein College of Medicine in the Bronx presented data of their study of over 70,000 postmenopausal women who were followed annually for 22 years. Ten percent of them had a history of migraines (compared to 18% seen in surveys of all women). Surprisingly, those with a history of migraine did not have a higher risk for strokes or heart attacks.

This somewhat contradicts another study mentioned on this blog last year. Doctors in South Carolina established that people with migraine with aura who were 60 or older, were more likely to have atrial fibrillation (a type of arrhythmia, or irregular heart beat), a condition that increases the risk of strokes.

Despite some inconsistencies in various studies, the practical implications are that those with migraines (and those without) should try to control modifiable risk factors. These include smoking, high blood pressure, diabetes, high cholesterol. If atrial fibrillation is present, a blood thinner is usually indicated as it may prevent strokes. Control of modifiable risk factors includes not only medications, but also regular exercise, healthy diet, stress management, and good sleep habits.

Probiotics for migraine

By: Dr. Mauskop

03-08-2019

Alternative Therapies, Chronic migraine, Migraine

Many migraine sufferers have gastro-intestinal problems, such as irritable bowel syndrome, constipation, sensitivity to gluten, dairy, and other types of foods. Nausea and vomiting and gastric stasis are common symptoms of migraine. All this indicates a close relationship between the gut and migraines. Considering that we contain more bacterial cells than our own (you may want to read a fascinating book by Ed Yong, I Contain Multitudes: The Microbes Within Us and a Grander View of Life), it is not surprising that certain types of bacteria may help prevent migraines.

Bio-Kult is a probiotic that contains 14 different strains of bacteria. It was tested for the prevention of migraine headaches in a double-blind placebo-controlled trial. I mentioned the preliminary results of this study presented in 2017 at the International Headache Congress, but the final results were only recently published in Cephalalgia. The researchers enrolled 100 patients and placed 50 of them into the placebo group and 50 into the probiotic group. 43 patients on the active therapy and 36 on placebo completed the trial. Patients with both chronic and episodic migraines (15 or more headache days a month makes it chronic) were included.

After 2 month of treatment, the mean frequency of migraine attacks and their severity were significantly reduced in the probiotic group compared to the placebo group. There was also a significant reduction of the number of abortive migraine medications taken by those in the probiotic group.

This was a small study with a high dropout rate, which means that it is far from proven that this type of probiotic is effective in treating migraine headaches. However, considering the safety of this product and its reasonable cost ($21 for a month supply on Amazon.com), it is worth a try after or in addition to more proven supplements such as magnesium and CoQ10.

Although the study was conducted in Iran, Bio-Kult is manufactured in the UK, which assures good quality. It has received “The Queen’s Awards for Enterprise”.

100 Migraine Drugs, A to Z: ketoprofen

By: Dr. Mauskop

28-07-2019

Headache medications, Migraine

Ketoprofen (Orudis, the branded version, is no longer available) is a prescription nonsteroidal antiinflammatory drug (NSAID) without any outstanding features. Just like all other NSAIDs, it is effective for the acute treatment of migraine headaches.

A double-blind placebo-controlled randomized trial compared ketoprofen, 75 mg, 150 mg and 2.5 mg of zolmitriptan (Zomig). All three active therapies were equally effective in relieving migraines and were much more effective than placebo. This does not mean that ketoprofen and zolmitriptan are equally effective in any particular migraine sufferer because some people will respond better to an NSAID and other to a triptan. Also, the usual dose of zolmitriptan is 5 mg, so it is possible that even on average, a 5 mg dose might be superior to ketoprofen. We often combine a triptan with an NSAID such as ibuprofen (Advil) or naproxen (Aleve, Naprosyn) and ketoprofen can also be combined with a triptan.

Another double-blind study compared 100 mg ketoprofen suppository (a compounding pharmacy can prepare such a suppository) with 2 mg ergotamine suppository and ketoprofen was found to be superior to ergotamine. Since the introduction of triptans ergotamine has not been widely used because it causes more side effects, particularly nausea.

Just like with other NSAIDs, the most common side effects are gastrointestinal – heartburn, stomach pain, bleeding ulcers, etc. NSAIDs can also cause tinnitus (ringing in the ears), rashes, and with long-term use, kidney and heart problems.

Another promising acute therapy for migraines

By: Dr. Mauskop

24-07-2019

Headache medications, Migraine, New treatments

Dihydroergotamine (DHE-45) is a very old migraine drug in the family of ergot alkaloids. It is one of the most effective migraine drugs when it is given intravenously and it is often used when patients are admitted to the hospital for migraines that do not respond to other therapies.

Dihydroergotamine (DHE) is also available as a nasal spray (Migranal), but it works well only in a limited number of patients and is very expensive. This poor consistency of effect is partly due to the amount of liquid that needs to be sprayed for one dose, most of which is either swallowed or leaks out. A form of DHE to be inhaled into the lungs had been in development for many years, but is not likely to become available due to manufacturing difficulties.

A promising new way to deliver DHE as a nasal powder is being developed by Satsuma Pharmaceuticals. The company presented their preliminary data at the recently concluded scientific meeting of the American Headache Society in Philadelphia. Their study showed that powdered form of DHE delivered into the nose gets into the blood faster and better than the existing nasal liquid form, although not as well as when it is given as an intramuscular injection. The device to administer DHE is small and easy to use, unlike another device that is also being developed for intranasal delivery of DHE powder. The company is initiating a large clinical trial, which will hopefully lead to the approval of their product.

Erenumab for trigeminal neuralgia and other news from the American Headache Society meeting

By: Dr. Mauskop

18-07-2019

Chronic migraine, New treatments, Trigeminal and other neuralgias

The annual scientific meeting was held last weekend in Philadelphia. The largest number of presentations was about the CGRP drugs, both monoclonal antibodies (mAbs) for the prevention and soon to be approved oral medications for the abortive treatment of migraine attacks. In addition to the three currently available mAbs, erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), which are self-injected subcutaneously every month (Ajovy can be given every 3 months), a fourth intravenous mAb, eptinezumab, which is given every 3 month, is likely to come out early next year.

Two oral CGRP drugs that are in development are taken as needed for an individual attack of migraine. These drugs are rimegepant and ubrogepant and they are expected to be approved by the FDA in about 6 months.

One interesting presentation by N. George and Z. Ahmed from the Cleveland Clinic and other Cleveland hospitals described 8 patients with trigeminal neuralgia (TN) who also suffered from migraines and were given injections of erenumab (Aimovig). Six out of 8 reported good relief of their neuralgia along with migraines. It is possible that the neuralgia pain was part of their migraine, but it may still be worth trying erenumab in patients with TN who do not respond to standard therapies or Botox.

100 Migraine Drugs, A to Z: ketamine

By: Dr. Mauskop

04-07-2019

Headache medications, Migraine, New treatments

Ketamine (Ketalar) was officially approved for human use by Food and Drug Administration (FDA) in 1970 and, because of its wide margin of safety, was even administered as a field anaesthetic to soldiers during the Vietnam war. Concerns over the psychedelic effects of ketamine and the arrival of new intravenous hypnotics such as propofol led to a marked decrease in the use of ketamine for anesthesia, but in the recent years its use has been increasing. Its unique properties have led many researchers to do clinical trials for the treatment of pain and depression. Intranasal ketamine was just approved by the FDA for treatment-resistant depression.

True efficacy of ketamine for the treatment of pain and migraine headaches is less clear. There have been no double-blind studies of ketamine for the treatment of migraine headaches. A major obstacle to doing such studies is that it is very difficult to blind patients to the effect of ketamine. We do have anecdotal evidence, that is a description of series of patients who were given intravenous ketamine. A report entitled, Ketamine Infusions for Treatment Refractory Headache describes 77 chronic migraine patients who “failed aggressive outpatient and inpatient treatments”. These patients were hospitalized and were receiving ketamine infusions for an average of 5 days. Over 70% of these patients improved, although only 27% had sustained improvement.

In a report published in The Journal of Headache and Pain authors describe 6 patients admitted to the hospital whose refractory migraines improved with intravenous ketamine, albeit the improvement was only short-term. One patient reported a transient out-of-body hallucination, which resolved after decreasing the rate of infusion.

Intranasal ketamine was shown to relieve severe migraine aura in 5 of 11 patients with familial hemiplegic migraine. In some patients, the aura can be more debilitating than the headache or other symptoms of migraine and we have no effective treatment to stop the aura once it stops.

A Randomized Controlled Trial of Intranasal Ketamine in Migraine With Prolonged Aura, was a study of 18 patients published in Neurology. It showed that intranasal ketamine reduces the severity but not the duration of migraine aura.

I have referred a small number of patients whose migraines fail to respond to a wide variety of treatments for outpatient intravenous ketamine infusions. A few of these patients found ketamine to be very helpful. This is not a fair test of the drug’s efficacy because those who failed to respond to 20 different treatments are not likely to respond to the 21st one. Considering that ketamine is fairly safe (the dose given is much smaller than the dose used for anesthesia), it would be useful to have a controlled randomized trial in less refractory patients.

100 Migraine Drugs, A to Z: indomethacin

By: Dr. Mauskop

17-06-2019

Headache medications, Migraine

Indomethacin (Indocin) is one of the strongest non-steroidal anti-inflammatory drugs (NSAIDs), but unfortunately it is rarely used for the treatment of migraines. It has a higher chance of causing gastro-intestinal (GI) side effects than other NSAIDs, but some patients tolerate it very well, especially if it is used sporadically. The drug can be compounded into a rectal suppository, which reduces (but does not eliminate) GI side effects and provides faster onset of effect than an oral capsule. Even if nausea is not obviously present, migraine is often accompanied by gastric stasis, which means that absorption of oral drugs is slowed down. This is why pharmaceutical companies often try to formulate migraine drugs into nasal sprays, injections, patches and inhalers. Rectal route also bypasses the stomach, but suppositories are less popular in the US than they are in Europe. The dose of oral indomethacin is 25, 50 or 75 mg taken up to three times a day, while suppositories usually contain 50 mg.

Indomethacin has some unique properties that differentiate it from other NSAIDs and it is often the only NSAID that is highly effective for episodic and chronic paroxysmal hemicrania and hemicrania continua, rare conditions that are often mistaken for migraines. They are even described as indomethacin-sensitive headaches because no other drug provides such dramatic relief. Paroxysmal hemicrania also resembles cluster headache in that it is always one-sided and is often accompanied by nasal congestion and tearing on the side of the headache. Unlike cluster headaches, which last 30 minutes to 3 hours and occur once or a few times a day, the attacks of hemicrania last a few minutes but occur many times throughout the day. Hemicrania continua is also always one-sided and the pain is continuous without any pain-free periods. If indomethacin causes GI side effects, in some patients an anti-inflammatory herbal supplement, Boswellia can be as effective but without causing any side effects. Botox injections is another treatment that can provide relief of indomethacin-sensitive headaches.

100 Migraine Drugs, A to Z: ibuprofen

By: Dr. Mauskop

12-06-2019

Headache medications

Ibuprofen (Advil, Motrin, Nuprin, Nurofen, etc) is a very effective migraine drug. Of course, patients with severe migraines tell me that for them taking ibuprofen is like eating candy, but even those patients can get better relief if they add ibuprofen (or naproxen) to a triptan such as sumatriptan (Imitrex).

Over-the-counter ibuprofen (Advil Migraine, Motrin Migraine) is officially approved by the FDA for the treatment of migraines, which means that it has been studied in large placebo-controlled trials to prove that it is safe and effective. Ibuprofen was shown to be more effective than acetaminophen in children. The adult dose is 400 mg, while in children it is 10 mg per kilogram of weight.

Liquified form of ibuprofen (Advil Liquigels, Advil Migraine)) and liquid ibuprofen for children tend to work faster than a solid tablet.

Frequent intake of ibuprofen (and other NSAIDs and triptans) is thought to lead to medication overuse headache (MOH), but if this does occur, it is rare and the entire concept of MOH remains controversial. Only caffeine and opioid (narcotic) pain killers have been proven to worsen headaches if taken often. It is not to say that frequent or daily intake of ibuprofen is the best way to manage frequent migraines. Many preventive therapies such as Botox, magnesium, propranolol, and other may be more effective and safer. Frequent use of ibuprofen can cause kidney problems and stomach ulcers, which can bleed and even be fatal.

First drug approved for the prevention of cluster headaches

By: Dr. Mauskop

05-06-2019

Cluster headaches, Headache medications, New treatments

Galcanezumab (Emgality) was just approved by the FDA for the prevention of episodic cluster headaches. Galcanezumab is one of the three new drugs recently approved for the prevention of migraines (the other two are erenumab, or Aimovig and fremanezumab, or Ajovy). These are monoclonal antibodies (mAbs) that block CGRP, a chemical released during attacks of migraine and cluster headaches.

The manufacturer of fremanezumab also conducted trials for the prevention of cluster headaches, but could not prove that the drug was more effective than placebo. Galcanezumab was also tested for chronic cluster headaches and it did not seem to help. Only 10-15% of cluster headache sufferers have the chronic form. About 250,000 Americans suffer from cluster headaches. Compared to migraines, which affect over 35 million Americans, this is a rare disease. This makes it difficult to conduct clinical trials of new treatments. The only abortive drug approved for the treatment of an acute cluster attack is sumatriptan (Imitrex) injection.

The dose of galcanezumab for the prevention of migraines is 240 mg injection at the start and then, 120 mg every month. The dose for cluster headaches is 300 mg. Of the 106 patients in the cluster headache study only 2 stopped the drug because of side effects. Just like in migraine trials, which involved thousand of patients, the only side effect which occur in more than 2% of patients was injection site reactions, but serious allergic reaction can also occur.

Since erenumab was approved for migraines before the other two mAbs and because preliminary evidence suggested that these drugs may work for cluster headaches, we’ve tried erenumab and then, fremanezumab in our cluster patients who did not respond to usual therapy. Although our numbers are too small to make any sweeping conclusions, it appears that just like with migraines, two out of three patients obtain some benefit. Now that galcanezumab is officially approved, we will be using it for all of our cluster headache patients since insurance companies will have to pay for it. Based on our experience with these drugs in migraines, it is likely that the insurers will require that patients first try and fail some of the other preventive therapies, even if none of those have been approved by the FDA. The most commonly used drug for the prevention of cluster headaches is a blood pressure medicine in the calcium blocker family, verapamil. We also try to abort the entire cluster with an occipital nerve block or a course of prednisone, a steroid medication. Epilepsy drugs such as topiramate (Topamax) and a psychiatric drug, lithium can also help.

Cluster headaches affect more men than women and cause more severe pain than migraines, leading some to call them suicide headaches. Women do suffer from cluster headaches as well and they are more often misdiagnosed. Unfortunately men don’t fare well either – 46% of men are misdiagnosed, compared with 61% of women. It takes 5-6 years before the correct diagnosis is made. Cluster headaches are often mistaken for migraines because pain is on one side of the head and for sinus headaches because cluster headaches are usually accompanied by a runny nose.