Headache NewsBlog

FDA approves Qulipta (atogepant), a new preventive migraine drug

By: Dr. Mauskop

02-10-2021

Chronic migraine, Headache medications, Migraine

Atogepant (Qulipta) is a new migraine drug that was just approved by the FDA for the preventive treatment of migraines. It is the third drug in the family of gepants. Gepants block the CGRP receptor. CGRP is a chemical released during a migraine attack. In the past three years, the FDA approved four injectable preventive migraine drugs that also block CGRP. Gepants are taken by mouth.

The dose of atogepant is 10 mg, 30 mg or 60 mg taken daily, once a day. The primary efficacy endpoint in clinical trials was the change from baseline in mean monthly migraine days over the 12-week treatment period. There was a drop of 3.7, 3.9, and 4.2 in the number of mean monthly migraine days in the 10 mg, 30 mg, and 60 mg doses, respectively.

Side effects – assessed in almost 2,000 patients – were infrequent and mild. Nausea occurred in 5%, 6%, and 9% on 10 mg, 30 mg, and 60 mg respectively, constipation in 6% on all three doses, and fatigue or somnolence in 4%, 4%, and 6%.

Ubrogepant and rimegepant, two other gepants, were first approved to be taken as needed, whenever a migraine strikes. Rimegepant recently was also approved for the prevention of migraines. Even though gepants are very similar they often differ in how they work in an individual patient. Some of my patients find that ubrogepant works much better than rimegepant while for others the opposite is true. I am certain that some patients will find a big difference in the way rimegepant and atogepant work for them. This is why it is useful to have a few drugs in every therapeutic category.

A large study shows that the weather affects pain

By: Dr. Mauskop

27-09-2021

Alternative Therapies, Chronic migraine, Headaches, Migraine, Pain, Pain Research

Many migraine sufferers report that their migraines are brought on by the weather. High humidity, high temperatures, and changes in barometric pressure are the most commonly reported triggers. I’ve seen some patients for whom changes in the weather is the only trigger. Research studies looking at this connection, however, have been contradictory.

A very large study just published in Pain, the journal of the International Association for the Study of Pain examined a possible connection between the weather and pain tolerance.

The data from 18,000 Norwegians aged 40 years or older from the general population were examined. All of them underwent pressure pain tolerance (PPT) test using a blood pressure cuff and cold pain tolerance (CPT), tested by immersing the dominant hand in cold water.

The results showed a clear seasonal variation in CPT. Cold pain tolerance was worse during the warmer times of the year compared with January. There was no seasonal variation in PPT.

The authors also found that temperature and barometric pressure have “a causal and dynamic effect on pain tolerance, which supports the common belief that weather affects pain.”

There is not much you can do about the weather except for moving to a place with an unchanging and mild climate. Some of my patients with barometric pressure-induced headaches do respond to acetazolamide (Diamox). This is a diuretic that prevents mountain sickness in climbers. Patients do not need to constantly check the weather forecast. For more information on acetazolamide, see my previous blog post.

Migraines are less common in people with diabetes

By: Dr. Mauskop

18-09-2021

Uncategorized

Two large studies have established that if you have diabetes you are less likely to suffer from migraines.

The first study was done on the entire population of Norway. The authors concluded that both type 1 and type 2 diabetes are significantly associated with a decreased risk of migraine.

The second study involved 74,247 French women. The researchers discovered that there was a lower risk of developing type 2 diabetes in women with active migraine. They also found that migraine was less common even prior to the development of diabetes.

Being overweight increases the frequency of migraines. Losing weight by any method, including bariatric surgery, improves migraines. There have been no studies of diabetes drugs in the treatment of migraines.

However, I do prescribe a diabetes drug metformin to migraine patients who are overweight or develop migraines when they are hungry. Metformin helps lose weight by maintaining a steady level of blood sugar. It does this by regulating the release of glucose from the liver. It also has anti-inflammatory properties.

Another diabetes drug, semaglutide in injections (Wegovy and Ozempic) and tablets (Rybelsus) is even more effective for weight reduction than metformin. Semaglutide, unlike metformin, is approved by the FDA for weight loss even in the absence of diabetes.

It is possible that the treatment of diabetes reduces the risk of developing migraines. The French study, however, suggests that other factors could play a role as well.

Julie Mauskop on David Zwirner’s Platform

By: Dr. Mauskop

11-09-2021

Alternative Therapies

Patients coming to the New York Headache Center have enjoyed seeing my daughter Julie’s artwork since she was 11. This was not just a childhood interest – Julie graduated from the Rhode Island School of Design with a degree in painting. She has continued to work hard as a painter and her perseverance and talent have led to wider recognition.

Julie is represented by a New York City gallery, SHRINE. A few days ago, her work was selected for Platform, a new online initiative by David Zwirner.

You can see more of Julie’s work on her Instagram page.

A new, better DHE nasal spray is approved for acute migraines

By: Dr. Mauskop

06-09-2021

Chronic migraine, Headache medications, Headaches, Migraine, New treatments

Trudhesa is a new formulation of dihydroergotamine (DHE) nasal spray just approved by the FDA. It appears to be more effective than the original DHE nasal spray (Migranal) that was introduced in 1997.

Ergotamine, the first migraine-specific drug was developed in 1926. It is still available in tablet form but is not widely used because it causes nausea, constriction of blood vessels, and other side effects. DHE, approved in 1946, was the first synthetic migraine drug. It was derived from ergotamine in an attempt to reduce side effects. DHE is not effective when taken by mouth and was originally approved for intravenous use. It is still being used now – 75 years later – intravenously, intramuscularly, and subcutaneously. DHE injection is a very effective medicine, often used when no other migraine drug provides relief. It does cause nausea and vomiting in a significant number of patients. This is why it is often given along with an anti-nausea drug such as ondansetron (Zofran), prochlorperazine (Compazine), or metoclopramide (Reglan).

The original DHE nasal spray has been a relative disappointment. It is not very effective, although there are some patients for whom it works well. Despite being on the market for over 20 years, it is still very expensive – $100 a dose. The manufacturer of Trudhesa, which is a better product than Migranal, is promising to make their product more affordable. Nasal delivery of DHE causes less nausea than an injection.

Trudhesa is more effective despite delivering a smaller dose of DHE than Migranal. This is because Trudhesa is delivered as a fine mist into the upper reaches of the nasal cavity. It will become available in about two months. I will prescribe it to patients for whom oral medications are ineffective.

Placebo really works, even if you know it’s placebo

By: Dr. Mauskop

30-08-2021

Alternative Therapies, Headache medications, Headaches, Migraine, Pain, Pain Research, Psychology of headaches

The placebo effect is a bane of clinical trials. A drug is considered ineffective if it is only as good as a placebo. And placebo can be quite good. Intriguingly, the placebo effect in clinical trials has been getting stronger over the past few decades. Lately, placebo has been receiving a lot of attention from researchers.

A rigorous study just published in the journal Pain looked at the effect of a placebo when patients were clearly told that they are taking a placebo. These patients were compared to those who were given a placebo in a double-blind study of peppermint oil capsules for irritable bowel syndrome (IBS). These two different types of placebo were compared to a control group of patients who were not given any pills.

Participants treated with an open-label placebo and a double-blind placebo reported similar and clinically meaningful improvements in IBS symptoms. These improvements were significantly greater than in those who were not given any pills. The results were statistically significant for the primary outcome measure (IBS Symptom Severity Scale) as well as for mean global improvement scores.

Twice as many patients in the double-blind placebo group had side effects (mostly gastrointestinal, such as heartburn) than those in the open-label placebo. It is probably because the first group was told about the possible side effects of peppermint oil.

The authors concluded that an open-label placebo “could play a role in the management of patients with refractory IBS”.

Just like migraines, IBS involves central sensitization and hypersensitivity of the nervous system. And just like with migraines, placebo response in clinical trials of IBS tend to be high. This is not to suggest that these conditions are psychological. Especially with migraines, the biological basis is well documented. Psychological factors, however, cannot be ignored. About 40% of patients with chronic pain, including migraines, have a history of emotional, physical, or sexual abuse. Post-traumatic stress disorder of other types also causes hypersensitivity of the central nervous system. Psychological factors can even be the cause of such potentially deadly conditions as broken heart syndrome (Takotsubo cardiomyopathy). It is likely that the placebo effect is stronger in conditions where psychological factors are more pronounced.

It is considered unethical to prescribe a placebo to patients without telling them that they are getting a placebo. This latest study suggests that some patients may improve even if they know that they are taking a placebo.

I do prescribe herbal supplements such as feverfew and boswellia and on a rare occasion, a homeopathic remedy, all of which lack rigorous proof of their efficacy. For that matter, many drugs we prescribe for migraines lack such definitive proof. I would suggest that we should first prescribe less harmful unproven remedies rather than unproven prescription drugs.

Another review of The End of Migraines: 150 Ways to Stop Your Pain

By: Dr. Mauskop

22-08-2021

Chronic migraine, Migraine, Science of Migraine

It is gratifying to know that my colleagues consider my new book, The End of Migraines: 150 Ways to Stop Your Pain, to be useful for patients with migraines as well as doctors who treat them.

Dr. Uwe Reuter of Charité Universitätsmedizin Berlin, Germany has published a review in the latest issue of the journal of the International Headache Society, Cephalalgia. He concludes his review, “I am happy to encourage everybody who is interested in migraine to read this e-book.”

Dr. Allan Purdy published a review of my book in May in the journal of the American Headache Society, Headache. His review was much longer and so was the conclusion:
“I would recommend this book to anyone who has migraine or cares for people with migraine and wants a broad and sometimes detailed overview of the treatments. Available in the e-book format, it represents a lot of work for one person, but his passion, occasional humor, and historical perspectives are evident in this work. You don’t have to agree or accept everything the author says to enjoy and benefit from this “book,” and I know he would want people to be critical and skeptical where warranted. However, you will find more than you would usually need to know from this banquet of 150 ways to help your migraines! Enjoy, I did very much. Read it through once and save as reference.”

If you do read this book, please write a short review on Amazon.com.

More of the omega-3 and less of omega-6 fatty acids helps migraines

By: Dr. Mauskop

08-08-2021

Alternative Therapies, 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.

Magnesium can reduce the risk of aneurysm formation and rupture

By: Dr. Mauskop

02-08-2021

Alternative Therapies, Brain disorders

Many patients with headaches are concerned about having a brain aneurysm. It is rare for an aneurysm to cause ongoing headaches. An aneurysm usually causes one very severe headache when it ruptures and causes a brain hemorrhage. Half of the patients with a ruptured aneurysm die and many of those who survive have persistent neurological problems. This is why detecting and treating an aneurysm before it ruptures is the goal. Because aneurysms have a genetic component we do angiograms in close relatives of someone with a ruptured or unruptured brain aneurysm. About 2% of the population has brain aneurysms. It would be prohibitively expensive to subject everyone to a screening angiogram.

Aneurysms are the result of an outpouching of a weak spot in an artery. This process is very gradual and aneurysms tend to get bigger with age. People with small aneurysms and high blood pressure are advised to control their blood pressure in the hope that this will prevent or slow down the growth of the aneurysm. Small aneurysms rarely rupture. If an aneurysm is larger than 5 millimeters in diameter, however, the risk of rupture becomes significant and surgery or non-surgical obliteration is recommended.

Until now, there have been no interventions proven to reduce the risk of aneurysm formation and rupture.

In the current issue of Neurology, a group of Swedish researchers published a rigorous study entitled, Association of Serum Magnesium Levels With Risk of Intracranial Aneurysm.

They provided evidence showing that higher serum magnesium concentrations reduce the risk of intracranial aneurysm and aneurysmal rupture. This was only partly due to the blood pressure-lowering effect of magnesium. They speculated that the additional effects were due to the improved function of the blood vessel lining (endothelium) and a reduction in oxidative stress – proven actions of magnesium.

They concluded: “These findings add to the growing body of evidence highlighting a beneficial role of higher magnesium for preventing cerebrovascular and cardiovascular diseases.” These diseases include strokes, heart attacks, cardiac arrhythmias, and certainly, migraines. Besides these diseases, magnesium is very helpful in a host of other conditions such as asthma, diabetes, osteoporosis, obesity, and many others.

In 2012, I wrote an article, Why all migraine patients should be treated with magnesium. Considering that one-third of the population is deficient in magnesium, it would not be inappropriate to say that everybody should be taking a magnesium supplement.

Naratriptan is the most effective triptan?

By: Dr. Mauskop

26-07-2021

Chronic migraine, Headache medications, Migraine

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.

Chronic pain causes cognitive decline

By: Dr. Mauskop

17-07-2021

Brain disorders, Chronic migraine, Pain, Pain Research

Many patients with chronic migraines complain of memory, word-finding, and other cognitive difficulties. I tell them that once we find an effective treatment for their migraines, their cognitive abilities should improve. I explain that the barrage of pain messages disrupts the normal flow of information in the brain.

“Association between chronic pain and long-term cognitive decline in a population-based cohort of elderly participants” is the title of a study published in a recent issue of the journal Pain. The French researchers followed elderly chronic pain patients for up to 15 years.

They concluded that “Chronic pain is associated with a higher cognitive decline, particularly in processing speed. This result reinforces the importance of actively treating chronic pain with pharmacological and nonpharmacological strategies to prevent its consequences, including cognitive consequences.”

This also applies to chronic migraines. Fortunately, we have many new and not so new highly effective pharmacological and non-drug therapies that can provide relief to well over 90% of chronic migraine suffers. Check out my new book, The End of Migraines: 150 Ways to Stop Your Pain.

Occipital nerve stimulation relieves chronic cluster headaches

By: Dr. Mauskop

10-07-2021

Alternative Therapies, Cluster headaches, neurostimulation

The pain of cluster headaches is considered to be the worst of all headaches. Hence the moniker, suicide headaches. Thankfully, it is a rare condition. Episodic cluster headaches affect a little over 0.1% of the population or approximately 400,000 Americans. Of these, about 15% suffer from chronic cluster headaches. The division of cluster headaches into chronic and episodic is arbitrary, just like it is with migraines. Cluster headache attacks occurring for one year or longer without remission, or with remission periods lasting less than 3 months are considered to be chronic. Patients often go from episodic into chronic and back into episodic.

The term cluster comes from the fact that headaches occur daily or several times a day for a few weeks or months and then stop for a year or so. The attacks are always one-sided and the pain is localized around the eye. It can be associated with tearing, droopy eyelid, and nasal congestion on the side of pain. Some patients also have redness of the eye, sweating of the face, and tenderness in the back of the head.

These headaches are often misdiagnosed as migraine or sinus headaches. It can take several years before a patient receives the correct diagnosis and appropriate treatment.

The only FDA-approved preventive treatment is monthly injections of galcanezumab (Emgality). It came Verapamil, a calcium channel blocker used for hypertension, is another very effective drug. The dose of verapamil for cluster headaches is much higher than for hypertension – up to 960 mg a day. The only FDA-approved treatment for the treatment of individual attacks is sumatriptan (Imitrex) injections. Inhalation of pure oxygen through a mask at high flow (10-12 liters per minute) helps abort attacks in about 60% of patients. A course of steroids, such as prednisone, can sometimes stop the cluster period. These treatments are less effective for chronic cluster headaches.

Another treatment that can stop cluster attacks is an occipital nerve block. It is usually done with a steroid drug and a local anesthetic. The efficacy of this treatment led researchers to try electrical stimulation of the occipital nerve (ONS). It has been also tried in chronic migraines with mixed results.

Conducting trials of electrical stimulation presents big challenges. It requires surgical implantation of the stimulating wire next to the occipital nerve and the battery-operated device under the skin. It is impossible to disguise the sensation patients get from the electric current. They need to feel the stimulation in order for it to be effective.

A study just published in the journal Lancet compared strong and weak stimulation. The authors, led by Leopoldine Wilbrink, deserve great credit for conducting this difficult study. Despite the rarity of chronic cluster headaches, they were able to enroll 150 patients over a period of seven years. After a 12-week baseline observation, the patients were treated for 24 weeks.

The results showed that both weak and strong stimulation were equally effective. About half of the patients in each group had a 50% decrease in attack frequency. The most common side effects were local pain, impaired wound healing, neck stiffness, and hardware damage.

Another study by French researchers, Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache, was published last year in Neurosurgery. The mean duration of treatment observation was 44 months. Attack frequency was reduced by more than 50% in 69% of patients. Mean weekly attack frequency decreased from 22.5 at baseline to 10 after ONS. Functional impact, anxiety, and quality of life significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and quality of life dramatically improved from 38/100 to 73/100. 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or lead fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%).

ONS is a relatively safe treatment option for patients with chronic cluster headaches who do not respond to standard therapies. It is certainly safer than deep brain stimulation that has been reported to help some patients. Before resorting to ONS, I would also first try Botox injections, which I find to be effective in about a third of patients.

Besides ONS, vagus nerve stimulation (VNS) deserves further study. Two of my patients with severe chronic cluster headaches responded well to implanted VNS. This report led researchers to develop a non-invasive device to stimulate the vagus nerve. It was shown to be effective for episodic but not chronic cluster headaches. In my experience, however, it is only modestly effective even in episodic cluster headaches and is prohibitively expensive. The implanted VNS provides continuous stimulation. The non-invasive VNS is applied for only two minutes at a time. Future studies could compare the efficacy of ONS and implantable VNS.