Zavegepant nasal spray (Zavzpret) was just approved by the FDA for the acute treatment of migraines. It belongs to the family of gepants. These drugs abort migraine attacks by blocking the CGRP receptor. CGRP (calcitonin gene-related peptide) is released during a migraine attack. Blocking this molecule or the receptor it attaches to relieves migraines in about 50% of people.
There are four CGRP monoclonal antibodies, or mAbs, that are injected once every one or three months to prevent migraine attacks. Gepants are taken by mouth. Two of them – ubrogepant (Ubrelvy) and rimegepant (Nurtec) – are approved for the acute treatment of migraine attacks. Rimegepant, along with atogepant (Qulipta), is also approved for the prevention of migraines.
Nasal sprays to treat migraines have the advantage of faster onset of action. They are particularly useful for people who have nausea or vomiting and have difficulty absorbing or holding down oral medications. Other migraine drugs in a nasal spray include sumatriptan, zolmitriptan, dihydroergotamine, and ketorolac. For patients for whom these older drugs are ineffective, cause side effects, or are contraindicated, zavegepant could be a very good option.
If there are no contraindications for the use of a triptan (e.g. heart or other vascular diseases), I would use sumatriptan first because of the cost. It is also likely that insurance companies will require that the patient fails sumatriptan before they agree to pay for a new and more expensive drug. This is what they usually require before paying for oral gepants.
Here is a list of what I consider to be the top 10 acute medications to treat migraine from the second edition of my book, The End of Migraines: 150 Ways to Stop Your Pain. I might add zavegepant to the next edition of this book.
- Sumatriptan
- Rizatriptan
- Eletriptan
- Naratriptan
- Zolmitriptan
- Rimegepant
- Ubrogepant
- Aspirin/caffeine/acetaminophen
- Naproxen
- Ibuprofen
I am honored to speak at this year’s Migraine World Summit on Sunday, March 12. My topic is Safety Update: DHE, Triptans, Magnesium, Butterbur, and more.
The Migraine World Summit gives you a chance to improve your understanding of migraine headaches. 2023 dates: March 8-16. Register for free access at MigraineWorldSummit.com Call: 8885256449, Email: info@migraineworldsummit.com Facebook: www.facebook.com/MigraineWorldSummit/ Instagram: @migrainesummit
Read More
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.
Read MoreOn 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.
Read MoreIn a recent blog post, I wrote about the benefit of different types of exercises for the relief of migraines and other types of headaches. It mentioned that strength training may be more beneficial than aerobic (cardio) exercise. A study just published in Nature Communications suggests that the time of day when you exercise also matters. Not specifically for headaches but for “all-cause and cardiovascular disease mortality”.
This was a very rigorous study of 92,139 UK participants over an average of 7 years of follow-up which added up to 638,825 person-years. The timing of exercise was recorded by an activity tracker (accelerometer). Moderate-to-vigorous intensity physical activity at any time of day was associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. However, the morning group (5:00 – 11:00), midday-afternoon (11:00 – 17:00), and mixed timing groups, but not the evening group (17:00-24:00), had lower risks of all-cause and cardiovascular disease mortality.
This study suggests that exercising before 5 PM has more health benefits than exercising after 5. It is likely that this may also apply to the relief of migraines and other headaches.
Read MoreIn a post last August, I mentioned that zinc could possibly extend the duration of the effect of Botox. A new report by Chinese neurologists in Headache describes their findings of an inverse association between dietary zinc intake and the occurrence of migraine in American adults.
The researchers used the data from a five-year study conducted by the CDC to assess the health and nutritional status of Americans. Data were collected using a computer-assisted dietary interview system which proved to be very reliable. Over 11,000 adults were included in the analysis of zinc intake. These subjects were divided into quintiles, according to their zinc intake. The data were adjusted for various confounding factors. These included age, sex, race, ethnicity, smoking status, body mass index, and others.
People in the lowest quintile were at least 30% more likely to suffer from migraine compared to people in the other four quintiles. Associaion does not mean causation and this study does not prove that taking zinc will prevents migraines. However, a few small studies did show the benefit of taking a zinc supplement in migraine patients.
Checking your blood for zinc levels before taking a supplement would be ideal. However, there is very little downside to taking 10-25 mg of zinc daily even if you don’t know your zinc level.
Zinc is very important for the normal functioning of the immune system, it possibly prevents macular degeneration, and has many other benefits. Taking too much zinc can cause serious side effects. The effects of zinc toxicity are mostly due to the lowering of copper levels.
Read More
GABA, or gamma-aminobutyric acid, is a popular supplement for the relief of anxiety and insomnia. Until recently, I was not recommending it to my patients. There are no scientific studies showing that it works. So why did I start recommending it? A report by a single patient, or as we say in scientific literature, an N of 1.
This 65-year-old woman had been suffering from anxiety from a young age. When her summer camp friends would write down everyone’s most common sayings, hers was, “I am so nervous”. This sense of anxiety persisted throughout her life. She is a successful career woman with a loving family. After a death in her family, she started seeing a psychologist who suggested taking GABA for insomnia. Within days, she was overcome by a sense of calmness she never experienced in her life. It’s been several months now and she remains calmer than ever before.
Certainly, this could be a placebo effect. In addition to the lack of controlled clinical trials, it is not even clear if GABA gets into the brain by crossing the so-called blood-brain barrier (BBB). It is possible, however, that it does not have to cross BBB. There is evidence that GABA may work through the enteric nervous system (ENS) – nerve endings lining the intestines. Both GABA and its receptors are widely distributed in the gut. Certain probiotics such as Lactobacillus and Bifidobacterium were found to increase GABA concentrations in the ENS. Probiotics have been shown to improve mood. This effect may be occurring through the vagus nerve. Vagus nerve is a large nerve that connects the intestines and all internal organs with the brain. It was somewhat of a surprise that vagus nerve stimulation at the neck level was proven (and FDA-approved) to relieve refractory depression and epilepsy.
GABA has been a popular supplement for many years. This obviously does not prove that it really works. However, it is very safe and relatively inexpensive. I would consider trying it before taking a prescription drug for anxiety or insomnia. Those can have significant side effects and in a 65-year-old may increase the risk of Alzheimer’s disease. And I always recommend regular exercise and meditation before any supplements.
Read MoreThank you, Lisa Robin Benson for a kind review of my book. This is a video review on the Migraine.com website.
Many of my colleagues have written very positively about my book. It is even more gratyfing to hear that patients and patient advocates also find it useful.
Read MoreInsomnia is a very common problem. Sleep aids, over-the-counter and prescription have been proven to be harmful if taken long-term. They even raise the risk of Alzheimer’s.
A small dose of melatonin (300 mcg, or 0.3 mg) can help better than the usual 3 mg dose sold in most stores. You can also try valerian root and definitely adhere to sleep hygiene. This includes no reading or watching TV in bed, no screens for at least an hour before bedtime, no eating or exercising within two hours of going to bed, and sleeping in a cold room (65 to 68 degrees). Going to bed at the same time also helps.
If you still can’t fall asleep, try visualization. Actually, you don’t just use your visual memory but engage all the senses. This post was prompted by a WSJ article on this topic, A Happy Memory Can Help You Fall Asleep, if You Know How to Use It.
I usually imagine myself on a beach in a hammock under a tree, feeling a warm breeze on my body, seeing a beautiful view of the beach and the ocean, smelling fragrant flowers, and hearing the sound of waves lapping at the shore.
Once you find your happy place and can vividly recreate it, always use the same setting without variation. This way you will fall asleep within minutes.
Read More
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.
Read MoreMigraine 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.
Read More
Recent Comments