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Chronic migraine

Updated on 3/5/23

Even the best migraine medications work for only about half of the people who try them. In the next decade or so, advances in pharmacogenomics, neuroscience, and artificial intelligence will allow us to predict who is going to respond to which drug. This will eliminate the trial-and-error approach we have to use now.

German researchers led by Dr. Uwe Reuter just published a study that attempts to predict who is going to respond to injections of CGRP monoclonal antibodies (mAbs) that are used for the prevention of migraines. These drugs include erenumab (Aimovig), galcanezumab (Emgality), and fremanezumab (Ajovy). The fourth drug in this family that is given intravenously, eptinezumab (Vyepti) was not available in Germany at the time of the study.

They compared super-responders (patients with 75% or greater reduction of monthly headache days) with non-responders (patients with 25% or lower reduction of monthly headache days after trying all three mAbs). Of 260 patients with chronic and episodic migraine they evaluated, 11% were super-responders, and 10% were non-responders.

Non-responders were more likely to have chronic migraines. Super-responders were significantly more likely to report good improvement of their acute migraine headache with a triptan. Non-responders were more likely to have depression and overuse acute medications.

It was interesting that only 10% of patients were non-responders. The authors explained this by the fact that they had to fail all three mAbs to be considered non-responders. An earlier German study showed that one-third of patients who did not respond to erenumab did respond to galcanezumab or fremanezumab.

The low number of super-responders to mAbs could be due to the fact that the German government pays for this treatment only if there is treatment failure or intolerable adverse events with all first-line preventives (beta-blockers, topiramate, flunarizine, amitriptyline and for chronic migraine, also OnabotulinumtoxinA, or contraindications to those. In the large clinical trials that led to the approval of mAbs, there was no such requirement and the results were much better.

Another study recently published by Sait Ashina and others in Rami Burstein’s group at Harvard showed that people who have increased skin sensitivity between migraine attacks (allodynia) are more likely to respond to galcanezumab.

These studies describe only trends and at this time have limited practical application. Patients who are depressed, overuse acute drugs, suffer from chronic migraines, or have interictal allodynia may still respond to mAbs. This information, however, may lead to more accurate prediction models when it is combined with genetic, imaging and other new data.

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On March 10, I will be speaking on the Treatment of a Refractory Headache Patient at the annual meeting of HCNE in Greenwich, CT. One of the seven broad strategies I will be speaking about is trying multiple drugs within each therapeutic category. For example, if you did not respond to one beta-blocker, a different one might work better or have fewer side effects. Here is a part of a recent email from a former patient that supports this idea.

“For over fifty years, I have had migraines. Ever since Imitrex came out and I started to take it, I would get a migraine every day! We thought it might be rebound headaches from the Imitrex, but it was not. I tried every kind of medicine, and I mean EVERY. Nothing worked, and I just figured this was the way it would be until I died.
This summer, my hand was hurting and the doctor prescribed Celebrex. It did not help my hand, but my migraines WENT AWAY!!! Yes, after 50 some-odd years, no migraines. I thought it was a fluke, but no… my migraines are gone.
I take a Celebrex every morning after breakfast. If I even start to feel a headache, I take 2 Advil, and the headache is gone for the day. Every once in a while, I do get a migraine and I will take sumatriptan, but it is rare.”

Celebrex, or celecoxib, belongs to the NSAID family. It is somewhat different from other NSAIDs in that it is a selective COX-2 inhibitor. This means that it has fewer gastrointestinal side effects (ulcers, heartburn, etc.). Many people find that one NSAID works for an acute migraine much better than another – naproxen is better than ibuprofen, or diclofenac is better than naproxen, etc. This also holds true for the use of NSAIDs in the prevention of migraines. Meloxicam, indomethacin, aspirin, mefenamic acid, and others have been reported to be uniquely effective for some of my patients.

You can read about almost every drug in every category in the second edition of my latest book, The End of Migraines: 150 Ways to Stop Your Pain.

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Another excellent educational course for healthcare professionals will be held on March 10th and 11th in Greenwich, CT. The Headache Cooperative of New England has held these symposia for over 20 years. 

The topic of my presentation is The approach to the Refractory Headache Patient. In addition to the East Coast headache specialists, several notable headache experts from the West Coast will be presenting as well – Dr. Morris Levine, the director of the UCSF headache center and Dr. Robert Cowan of Stanford.

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Migraine surgery is controversial. I would not consider it until most of the less invasive options have been tried. In my latest book, I give migraine surgery a score of 3, on a 1 to 10 scale. This rating may not be fair because clinical trials suggest that it can be very effective for some patients.

So, when is a referral to a surgeon warranted? Dr. Lisa Gfrerer is highly qualified to address this topic. She will speak on January 25th at a dinner of the NY Headache Club, an informal gathering of headache specialists who practice in the greater NYC area. If you are a headache specialist and would like to attend, send me a message. The meeting is not open to the lay public.

Here is Dr. Lisa Gfrerer’s short bio.

Dr. Gfrerer is an Assistant Professor in Plastic and Reconstructive Surgery at Weill Cornell Medicine (WCM). She received her MD degree at the Medical School of Vienna prior to completing a PhD in Genetics at the Harvard Stem Cell Institute. She graduated from the Harvard Integrated Plastic Surgery Residency Program and completed the Advanced Peripheral Nerve and Microsurgery at the  Massachusetts General Hospital (MGH). Clinically, her focus is peripheral nerve surgery including headache surgery, treatment of nerve pain and compression, breast reinnervation, as well as advanced nerve reconstruction for restoration of motor and sensory function after an iatrogenic and accidental injury. She has built a multi-institutional and multidisciplinary research program for headache surgery, breast/chest reinnervation, as well as functional nerve disorders and nerve pain. As an affiliate of the Massachusetts Institute of Technology (MIT) she has further focused on innovation and device development to enhance peripheral nerve regeneration.

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Opportunities & Challenges in the Management of Headache is one of the two annual courses organized by the Diamond Headache Clinic Research & Educational Foundation. This year, it will be held in San Diego from February 16th through February 19th.

The other annual event, Headache Update 2023 will be held in Orlando, Fl from July 13th through July 16th. Both courses have been always well attended and have been receiving very high marks from the attendees.

It’s been my privilege to participate in these annual courses over the past 25 years. This year I will be speaking on February 17th on Nutritional Approaches and Alternative Therapies in Migraine.

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According to a new report by Spanish researchers published in The Journal of Headaches and Pain, effective preventive treatment of migraines can improve cognitive impairment in patients with frequent attacks.

Patients with migraines often complain that their memory is not as good as it used to be, that they have difficulty concentrating, or can’t think clearly.

There are many possible causes of such symptoms. Stress is probably the most common reason people have trouble with memory and concentration. There is just too much on their mind. Certain drugs, most notably topiramate (Topamax), can cause pronounced cognitive impairment.  Nutritional deficiencies, particularly of vitamin B12 and other B vitamins, magnesium and vitamin D can cause brain fog and other cognitive problems. Alzheimer’s disease, which is what people fear most, thankfully is rare at the age when most people suffer from migraines.

I also see patients who do not have any of the above reasons. There are several possible explanations for why migraines alone can cause cognitive problems. We know that if a patient has only a few attacks a month, the brain remains hyperexcitable even between attacks. Some patients have a prodrome – one or two days of brain dysfunction prior to an attack. Others have post-drome – a feeling of exhaustion as if being hungover for a day or two after the attack. There is also a likely contributing effect of anticipatory anxiety – living in fear of the next attack.

Christina Gonzalez-Mingot and her colleagues in Lleida, Spain, compared 50 control subjects and 46 patients with chronic migraine. These patients were evaluated using a battery of tests prior to the use of preventive treatment based on botulinum toxin (Botox) or oral drugs and after 3 months of this treatment.

Compared with controls, patients with chronic migraine had lower scores on three standard tests of cognitive performance and had lower quality of life. Three months after the use of preventive treatment, improvement was observed in all but one cognitive parameters and in the quality of life.

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Psychedelics are being actively studied for depression and post-traumatic stress disorder (PTSD). These trials usually involve hallucinogenic doses. Microdosing psychedelic substances such as psilocybin, lysergic acid diethylamide (LSD), and methylenedioxymethamphetamine (MDMA) has become a popular treatment for depression. Microdosing means that the amount of a psychedelic is too low to cause hallucinations or other overt sensory experiences.

There is an accumulation of evidence that psychedelics can provide pain relief. A case series just published in the journal Pain describes three patients with chronic pain who obtained significant relief from microdosing psilocybin-containing mushrooms.

The first patient was a 37-year-old man with severe pain due to traumatic quadriplegia. He had almost complete relief of pain and was able to stop taking tramadol, an opioid analgesic, diazepam (Valium), and marijuana. The relief was ongoing for six months when he was last seen by the doctors.

The second patient was a 69-year-old woman with complex regional pain syndrome (also known as reflex sympathetic dystrophy) secondary to left leg trauma. She had tried nerve blocks, other invasive procedures, stem cell injections, acupuncture, opioid analgesics, and many other medications, all with no relief. At the time of the published report, microdosing was providing continued significant relief for over a year.

The third patient was a 40-year-old woman with pain in her leg due to degenerative disk disease in her spine. Her pain did not improve with epidural injections, back surgery, muscle relaxants, opioid drugs, and physical therapy. Psychedelic mushrooms had a profound effect on her pain.

Psychedelic mushrooms have been reported by many patients to be effective in the treatment of cluster headaches (see ClusterBusters.org). A small double-blind study by Yale researchers showed a beneficial effect of synthetic psilocybin in treating migraine headaches.

It remains to be proven that sub-hallucinogenic doses of psychedelic drugs provide relief of painful conditions. If proven effective, however, such drugs will offer a much safer option than any opioid and NSAID analgesics, epilepsy drugs, antidepressants, or any other prescription drug. They are very safe even at hallucinogenic doses.

I am often asked about the practical side of using psychedelic mushrooms – where to buy them, how much to take, and for how long. Since the state of NY, unlike some other states, has not legalized or decriminalized the use of psychedelic mushrooms, I cannot answer these questions. Even if it was legal for me to do, I would not have reliable answers until clinical trials give us good data.

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It was an honor to speak in Israel at the 6th Annual International Headache Symposium along with past presidents of the International Headache Society, Drs. Messoud Ashina and Alan Rapaport, the current IHS president, Cristina Tassorelli, the president-elect, Dr. Rami Burstein, and other leading headache experts. The symposium was organized by the President of the Israeli Headache Association, Dr. Oved Daniel, and by Dr. Arieh Kuritzky.

 

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No, Daxxify is not really a competitor in the treatment of chronic migraines or any other medical condition. Daxxify, a new botulinum toxin, was just approved by the FDA only for cosmetic use. Daxxify does stand out from five other botulinum toxin brands in that its effect lasts longer. The other toxins are Xeomin, Dysport, Jeuveau, and Myobloc. Myobloc is approved only for medical conditions, Jeuveau only for cosmetics, and Xeomin and Dysport are approved for both cosmetics and a few medical conditions.

Initially, Botox was approved by the FDA in 1989 to treat eye problems. Since then, it has been approved for many medical and cosmetic indications, including chronic migraine. None of the other toxins are approved for such a wide range of indications. It remains by far the most widely used type of botulinum toxin with tens of millions of people treated for medical and cosmetic reasons.

Yes, having a longer-acting botulinum toxin is an advantage. You will need to have less frequent treatments. However, if you have any side effects, they will also take longer to go away. We are talking mostly about cosmetic side effects, such as droopy eyelids. When treating headaches, with proper technique, side effects are uncommon. These may include weakness of the neck muscles or, if treating TMJ syndrome, difficulty chewing.

Since Botox is approved by the FDA for chronic migraines, Botox is the drug insurance companies cover. Allergan (a division of Abbvie), the manufacturer of Botox, has many more years left on their patent to treat chronic migraines. Botulinum toxin is a biological product (made by bacteria rather than synthesized from chemicals) and every version of it is slightly different. This is why when Allergan’s patent to treat migraines expires, the competitors will have to conduct large trials to prove that their product is also effective for migraines.

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Headache is a common symptom of any infectious illness, including COVID. A group of Spanish researchers analyzed six published studies of headaches in adult Spanish COVID patients.

According to their review, headache is an early symptom of COVID. It typically lasts two weeks. Patients in these studies were followed for up to a year. One out of five patients had developed a headache that persisted for at least a year. Women and older patients were more likely to be affected. This persistent headache most often resembled chronic migraine. The pain was throbbing with associated sensitivity to light and noise, and worsening with physical activity.  The authors did not observe a difference between patients with and without prior history of headache. Patients with more intense headaches were more likely to develop a chronic headaches.

The published studies reviewed by the authors did not address the treatment of headaches. Considering that the persistent headaches resembled migraines, we tend to treat them as we do chronic migraines. This means the use of antidepressants, epilepsy drugs, blood pressure medications, Botox, triptans, and CGRP drugs (both oral and injectable). It is likely that with early and aggressive treatment, many patients would not have headaches persist for such a long time. Doctors in Europe are less likely to prescribe medications and use Botox in headache patients than we are in the US.

COVID vaccination also carries a risk of developing persistent headaches. As mentioned in a previous post, people who received Pfizer or Oxford-AstraZeneca vaccine were twice as likely to develop a headache as those who received the placebo. The headache in these patients also tended to resemble migraine.

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Last week I spoke to Dr. Amelia Scott Barrett, a neurologist and headache specialist based in Denver. She shares my interest in combining medications with various non-drug therapies. In our first conversation, we discussed the role of magnesium in treating migraines.

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The 6th Annual International Headache Symposium in Israel will be held at Daniel Hotel, Herzliya (8 miles from Tel Aviv), on October 27, 2022. THe symposium is organized by the President of the Israeli Headache Association, Dr. Oved Daniel and by Dr. Arieh Kuritzky.

I am honored to have been invited to speak alongside the President of the International Headache Society Dr. Messoud Ashina, Dr. Rami Burstein of the Harvard Medical School, and other leading headache experts. The topic of my presentation will be “What to do when nothing works”. Other topics to be discussed include, Molecular signaling pathway in migraine: update, (Messoud Ashina), Connecting the line between dizziness, occipital headache, muscle tenderness and the cerebellum (Sait Ashina), Open-label studies: do they have any value? (Cristina Tassorelli), and others.

You can see the full program and registration information on this website.

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