I am honored to participate in a symposium on headache management,
“THE CHALLENGE OF MIGRAINE AND CLUSTER HEADACHES”. The title of my presentation is The challenge of migraine: new perspectives in refractory cases
This interactive neurological conference will be held in-person on Thursday, November 4, 2021 at the Zurich Marriott Hotel, Zurich, Switzerland
Read MoreTo gain FDA approval a drug has to be shown to be better than a placebo. The placebo effect is a well-established psychological contributor to the efficacy of most treatments.
They evaluated chronic migraine patients who were treated with erenumab (Aimovig). Erenumab is a monoclonal antibody that targets CGRP, a neurotransmitter involved in the development of migraine attacks.
Monthly erenumab injections were given for one year to 75 patients with chronic migraine who had already failed at least three other oral preventive drugs. A full psychological evaluation assessed personality disturbances, mood and anxiety disorders, as well as childhood traumas, and ongoing stressors.
After 12 months of treatment, 53 patients had at least a 50% drop in the number of headache days per month. The other 22 did not. When compared to responders, non-responders were more likely to have personality disorders with anxious-fearful, avoidant, dependent, and obsessive-compulsive features. Non-responders were also more likely to suffer anxiety disorders and had a higher number of current major stressors.
A very practical application of these findings is that doctors need to address anxiety when treating migraine and chronic pain patients. I’ve seen a number of patients whose migraines improved with an SSRI antidepressant such as fluoxetine (Prozac) or escitalopram (Lexapro). SSRIs do not possess pain-reliving properties. However, they are good at relieving anxiety and so can indirectly improve migraines. Most of the time, I prescribe SNRIs such as duloxetine (Cymbalta) or a tricyclic antidepressant such as nortriptyline (Pamelor) because they relieve anxiety and can have a direct pain-relieving effect.
The old dogma in psychology was that you cannot change your personality. We now know that such change is possible. Different types of cognitive-behavioral therapy (CBT) can be very helpful. Swedish researchers showed that even a brief internet-based CBT can produce long-term changes in personality traits.
Read MoreAtogepant (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.
Read MoreMany 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.
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.
Read MoreTrudhesa 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.
Read MoreIt 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.
Read MoreIn 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.
Read MoreMany 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.
Read MoreIt’s been a few years since I wrote about meditation. There is little doubt that it helps migraine sufferers. Unlike drugs, meditation is harder to test in clinical trials. However, we do have many imaging studies showing the effect of meditation on the brain and specifically on pain.
Mindfulness-based stress reduction (MBSR) is based on the practice of meditation. It is more structured and usually consists of a fixed number of sessions. This makes it easier to study in research trials.
The results of such a clinical trial were recently published in JAMA Internal Medicine. The researchers compared MBSR with headache education. The study included 89 adults who experienced between 4 and 20 migraine days per month. The participants and the researchers analyzing the data were blinded as to which group patients were assigned to.
MBSR or headache education was delivered in groups that met for 2 hours each week for 8 weeks. Most participants were female and the mean number of migraine days per month was 7. They had severe migraine-related disability. The follow-up period was 36 weeks.
While MBSR did not improve migraine frequency more than headache education, it did improve disability, quality of life, self-efficacy, pain catastrophizing, and depression for up to 36 weeks.
MBSR courses are widely available online. However, you can also learn to meditate by reading a book. My favorite one is Mindfulness in Plain English by B. Gunaratana. In-person classes are also becoming again (after COVID) widely available. Tara Brach is a psychologist and a Buddhist who has a very good free meditation podcast. Many people like using apps. Headspace, Calm, and Ten Percent Happier are some of the more popular ones.
Read MoreThe international classification of headache disorders lists many different types of migraines – migraine with aura, hemiplegic, retinal, chronic, and others. Chronic migraine is present if a person has a headache on 15 or more days each month. If the headache is present on fewer than 15 days, the condition is called episodic migraine.
The division into chronic and episodic migraine is not based on any scientific evidence. Research by Dr. Richard Lipton and his colleagues showed that patients often cycle from chronic into episodic migraines and back. This happens even without any treatment.
They concluded: “Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients.”
One damaging aspect of having a category of chronic migraine as it applies to clinical practice is the fact that Botox is approved only for chronic migraines. I know from 25 years of experience injecting Botox that it works very well for some patients who have as few as four migraines a month. Unfortunately, insurance companies do not pay for Botox unless you have chronic migraine. This deprives many patients of this very effective and safe treatment.
The second very costly effect is on the research of new preventive drugs. The FDA requires a separate set of studies for chronic and episodic migraines. These additional trials of the four approved injectable CGRP monoclonal antibodies added many millions of dollars to the development costs. The trials showed good relief for both episodic and chronic migraine sufferers.
Hopefully, the next, fourth classification of headache disorders will eliminate the category of chronic migraines.
Read MoreA publication of the American Headache Society, Headache, The Journal of Head and Face Pain, has just published Dr. Allan Purdy’s most generous review of my new book, The End of Migraines: 150 Ways to Stop Your Pain.
I am very grateful to Dr. Purdy and to my many colleagues who wrote endorsements for this book.
Self-publishing allows me to set a low price of $3.95 for the ebook version. It also makes it easy for me to regularly update it. Self-publishing, however, means that, unlike my previous three books, this one does not have the promotional help of a big publisher. If you read the book, please write a review on Amazon and spread the word to other migraine sufferers.
Read MoreBiohaven, the manufacturer of rimegepant (Nurtec ODT) just received FDA approval to market this drug for the prevention of migraines. Rimegepant was approved in January of 2020 for the acute treatment of migraine headaches. It is the first drug to be approved for both acute and preventive therapy of migraines.
Rimegepant is one of six drugs that block the action of calcitonin gene-related peptide (CGRP). CGRP has many important functions in the body but the release of excessive amounts of it in the brain can trigger a migraine. Four of the CGRP migraine drugs are given by injection and they are used only for the prevention of migraine attacks. Rimegepant and ubrogepant (Ubrelvy) are taken by mouth as needed, whenever a migraine strikes. These are truly novel drugs that have dramatically improved the lives of many migraine sufferers.
Rimegepant stays in the body longer – it has a half-life of 10-12 hours, while ubrogepant’s half-life is 7-8 hours. Another difference is that rimegepant dissolves in your mouth (ODT after Nurtec stands for orally disintegrating tablet), while ubrogepant is a solid tablet that is swallowed.
In clinical trials, rimegepant was noticed to provide relief of migraine that persisted for up to 48 hours. Because of this sustained effect, the researchers decided to test this drug for the prevention of migraine attacks by giving it every other day. And rimegepant passed this test. The official FDA-approved label says that for the prevention of migraines, one tablet of rimegepant should be taken every other day. For the acute treatment of migraines, the directions say to take 1 tablet a day, as needed.
The insurers typically pay for 8 tablets a month, although a few of my patients have been able to get 16. Now, with its approval for the prevention, patients will be able to get 16 tablets a month. It is possible that some patients may be able to get an additional 8 tablets for acute therapy. For most, however, 16 tablets a month should be sufficient.
The safety profile of rimegepant (as well as ubrogepant) is truly remarkable. The new rimegepant label states that “The most common side effects of NURTEC ODT were nausea (2.7%) and stomach pain/ indigestion (2.4%).” It also states that these are not the only possible side effects but their frequency is very low. Just like with any drugs, an allergic reaction is also possible.
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