injections | Headache NewsBlog

A novel migraine drug shows promise

By: Dr. Mauskop

08-09-2024

Alternative Therapies, Chronic migraine, Headache medications, Headaches, injections, Migraine, New treatments

Two sets of “designer drugs” have been developed based on our understanding of the neurobiology of migraines. The first, sumatriptan (Imitrex), introduced in 1992, was the pioneer in a class of seven triptan drugs, all targeting serotonin mechanisms. Erenumab (Aimovig), which targets the CGRP (calcitonin gene-related peptide) mechanism, was approved by the FDA in 2018. This class now includes four injectable, three oral, and one nasal drug. Additionally, many older drugs, although not specifically developed for migraine treatment, have proven effective for some patients. Despite these numerous options, a significant minority of patients do not respond to any of these treatments.

This is why the development of drugs targeting different parts of the migraine cascade is so promising. Danish neurologists, led by Dr. Mesoud Ashina, have published results from a phase 2 double-blind study of a new drug that blocks PACAP (pituitary adenylate cyclase-activating peptide).

In this study, patients were divided into two groups, receiving an infusion of a placebo or two different doses of the active drug, currently known as Lu AG09222, developed by the Danish company Lundbeck. In the final analysis, the reduction in migraine days was compared between 94 patients who received a placebo and 97 patients who received the higher dose of the active drug. The higher dose significantly reduced the number of migraine days in the month following the infusion (6.2 vs. 4.2 days reduction). The side effects reported were mild and infrequent.

Phase 2 studies are relatively small and short in duration. The FDA typically requires two large parallel studies involving a total of 1,000 or more patients before considering approval. Therefore, even if Lu AG09222 is found to be safe and effective, it may not receive approval for another 2-3 years.

If you are healthcare provider, attend the annual meeting of the Headache Cooperative of the Northeast

By: Dr. Mauskop

10-02-2024

Alternative Therapies, Blocks, Botox, Brain disorders, Chronic migraine, Head trauma, Headache medications, Headaches, injections, Migraine, neurostimulation, Psychology of headaches

I am once again honored to participate in the annual meeting of the Headache Cooperative of the Northeast to be held March 7-9 at the Stamford Marriott Hotel and Spa in Stamford, CT.

You will get a chance to learn about the latest scientific breakthroughs from Rami Burstein, president of the International Headache Society. You will also hear from other prominent figures in the field, renowned for their pioneering work and extensive contributions over several decades – Drs. Steven Baskin, Elizabeth Loder, Thomas Ward, Morris Levin, Richard Lipton, Steven Silberstein, Allan Purdy, Alan Rapaport, Paul Rizzoli, Sait Ashina, and others.

Attend the Diamond Research & Educational Foundation’s course

By: Dr. Mauskop

06-01-2024

Alternative Therapies, Blocks, Botox, Brain disorders, Chronic migraine, Cluster headaches, Head trauma, Headache medications, Headaches, Headaches in children, injections, Migraine, Migraine in pregnancy, New treatments, Science of Migraine

The annual course, “The Shifting Migraine Paradigm 2024” will be held February 15-17, 2024 at the Plaza San Antonio Hotel & Spa. This three-day conference offers an excellent update on the treatment of migraine and other headaches.

It is always an honor to be invited to speak at this event. The topic of my presentation is Supplements and Medical Foods.

New Daily Persistent Headache is very treatable

By: Dr. Mauskop

09-10-2023

Alternative Therapies, Botox, Brain disorders, Chronic migraine, Headache medications, Headaches, injections, Migraine, New treatments, Psychology of headaches, Science of Migraine

New daily persistent headache (NDPH) is condition that is defined solely by the fact that the headache begins suddenly one day and does not go away. There are no scientific studies to suggest possible underlying mechanisms or treatments. Some patients develop it after a viral infection while others, after a period of stress and many with no apparent trigger.

In my latest book, I mentioned how a seemingly benign idea of classifying medical conditions can cause harm. In case of NDPH, many anecdotal reports in medical journals indicate that this condition is not responsive to treatment. However, there are no controlled double-blind studies, only anecdotal reports. Many patients with this condition will look up this literature and conclude that there is no hope of getting better. I have seen many such devastated people. But this bleak picture is clearly wrong.

I have seen many patients with NDPH who responded to various treatments. In my 30 years of using Botox, I have found it to be one of the safest and most effective treatments for NDPH as well as migraine and other types of headaches.

At the recent meeting of the International Headache Society held in Seoul, two presentations described good responses of NDPH to Botox injections.

The first report was by S. Cheema and colleagues of Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK. They compared patients with NDPH (58) and those with chronic migraine (CM) with daily attacks (153) and chronic migraines without daily attacks (85). There was a 30% reduction in mean moderate and severe headache days in 33% of patients with NDPH, 43% with daily CM and 55% with non-daily CM.

The second report was by Shuu-Jiun Wang and colleagues of the Neurological Institute, Taipei Veterans General Hospital. They looked at the response of patients with NDPH who had predominately migraine features and those who had predominantly features of tension-type headaches. Of 228 patients diagnosed with NDPH, 199 patients (87%) had migrainous features and 29 patients (13%) had tension-type features. Their conclusion: “Through a mean follow-up duration of 2.5 years, around 40% patients with NDPH showed a favorable outcome at our headache center. Our results suggest NDPH might not be as grave as previously reported.”

Yes, these were also anecdotal reports rather than controlled trials, but they clearly show what I have also observed in my practice – NDPH is a very treatable condition. Hopefully, the next, fourth edition of the International Classification of Headache Disorders will no longer list NDPH as a diagnosis since it has no scientific basis.

Predicting response to migraine treatment

By: Dr. Mauskop

05-03-2023

Chronic migraine, Headache medications, injections, 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.

Migraine patients stick with Botox longer than with injections of CGRP mAbs

By: Dr. Mauskop

30-07-2022

Botox, Headache medications, injections, Migraine

Patients with chronic migraine who were started on Botox were significantly more likely to continue to be treated with Botox after one year than patients who were started on a CGRP monoclonal antibody (mAb). mAbs are given monthly by injection. This category includes erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality).

The results of this large retrospective study that included 1,974 patients were presented at the last meeting of the American Headache Society held in June of this year. The lead authors were Dr. Todd Schwedt of the Mayo Clinic and Dr. Andrew Blumenfeld.

The study was sponsored by the manufacturer of Botox which makes it inherently biased. However, the difference between the two groups was striking. Of patients who were started on Botox, 66% continued the treatment at the end of the year. Less than a third of patients who were started on a mAb were still getting it at the end of the year.

The researchers looked at differences in outcomes in patients enrolled before and during COVID. The results were similar before and during the pandemic. This is surprising because, during the pandemic, many patients were reluctant to come to the office for Botox injections. Many preferred to self-inject mAbs at home. Despite this obstacle, Botox patients were twice as likely to continue treatment at the end of the year.

Besides efficacy, the major reason I recommend Botox ahead of mAbs and other drugs is its proven long-term safety. Botox was first approved by the FDA in 1989. Botox is my preferred treatment for chronic migraines even in pregnant women.

Both mAbs and Botox are fairly expensive. The same group of researchers presented a second study that evaluated all-cause and migraine-related costs in these two groups of patients. They found no difference in total healthcare costs and migraine-related costs, including emergency department expenses.

CGRP monoclonal antibodies in pregnancy

By: Dr. Mauskop

09-05-2022

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

Not surprisingly, none of the new migraine drugs have been tested in pregnant women. No new drug for any indication is ever tested for its safety in human pregnancy. They are always tested in pregnant animals, which helps weed out most drugs that are clearly dangerous. It takes decades to learn if a drug is safe. This happens through an accumulation of anecdotal reports and pregnancy registries that are usually run by drug manufacturers.

Erenumab (Aimovig) was the first CGRP monoclonal antibody to be approved for the preventive treatment of migraines four years ago. It was tested in pregnant monkeys who were given 50 times higher doses (by weight) than the FDA-approved dose for humans. Even though some of the medicine crossed the placenta into baby monkeys, they had no developmental problems.

In the current issue of Headache, University of Texas doctors published a report of a woman who continued to inject herself with erenumab throughout the duration of her pregnancy. She tried to stop the drug before planning to get pregnant but her severe migraines recurred. Her baby was born healthy and had normal development by the last evaluation at 6 months of age.

This case report is the first very small but important step in the process of evaluating the safety of erenumab in pregnancy.

In humans, the transfer of antibodies, which are large molecules, across the placenta is very limited before the 16th week of pregnancy and increases after the 22nd week. We still recommend stopping the drug about five months before a pregnancy is planned. If a woman, however, does get pregnant, intentionally or not, the risk of complications is low if erenumab is stopped within the first three months of pregnancy. This also applies to all other monoclonal antibodies in general and specifically other migraine drugs – galcanezumab (Emgality), fremanezumab (Ajovy ), and eptinezumab (Vyepti).

Dr. Allan Purdy’s review of my new book

By: Dr. Mauskop

02-06-2021

Alternative Therapies, Blocks, Botox, Chronic migraine, Headache medications, Headaches, injections, Migraine, post-traumatic headache, Psychology of headaches, Science of Migraine

A 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.

Dramatic weight loss with a diabetes drug; may help migraines and other neurological problems

By: Dr. Mauskop

01-04-2021

Alternative Therapies, Chronic migraine, Headaches, injections, Migraine, Science of Migraine

Weight loss in overweight migraine sufferers – including that produced by bariatric surgery – leads to a reduction in the frequency of migraine attacks. In a previous post and in my new book I mentioned the use of metformin, a diabetes drug that helps weight loss, in migraine patients.

A study published in the February 10 issue of The New England Journal of Medicine definitively confirmed that weekly injections of another diabetes drug, semaglutide (Ozempic) can lead to an average of 15% weight loss in obese individuals. Seventy percent of participants lost at least 10% of weight. This was a double-blind, placebo-controlled trial that included 1,961 participants. Individuals in both the placebo and the active group were counseled every four weeks to encourage maintenance of a reduced calory diet and increased physical activity. Semaglutide is very similar to dulaglutide (Trulicity).

Other drugs that are used for weight loss produce an average of 4% to 6% weight loss and tend to have more side effects. Nausea and diarrhea were the most common adverse events with semaglutide. They were typically transient and mild-to-moderate in severity and subsided with time. Only 4.5% of participants on semaglutide stopped taking the drug due to side effects.

Obesity is a risk factor not only for diabetes and increased frequency of migraines but also strokes, idiopathic intracranial hypertension (pseudotumor cerebri), obstructive sleep apnea, hypertension, and others.

This trial should lead to the FDA approval of semaglutide for weight loss in obese individuals without diabetes. Hopefully, the FDA approval will compel insurance companies to pay for it. The out-of-pocket cost of 4 pen-like syringes is $735.

Histamine and migraine

By: Dr. Mauskop

17-08-2020

Alternative Therapies, Headache medications, Headaches, injections, Migraine

Histamine is best known as a part of the defense against allergies. But it is also an important neurotransmitter – a brain chemical involved in arousal, anxiety, the stress-related release of hormones, activation of the sympathetic nervous system, pain relief, and other functions.

Increased sensitivity to histamine may lead to an excessive allergic reaction which is relieved by anti-histamine drugs. It can also increase pain. One strategy thought to reduce this over-reaction is desensitization – injecting small amounts of histamine which can lead to a reduced reaction.

This approach seems to help some migraine and cluster patients. It was first reported in 1941 by a Mayo clinic doctor, Bayard Horton in an article entitled The use of histamine in the treatment of specific types of headaches. Another article, Intravenous histamine in the treatment of migraine was published in 1946 by W.A. Thomas and S. Butler.

A group of Mexican doctors compared subcutaneous (under the skin) injections of small doses of histamine to injections of placebo in 60 patients. They found histamine to be more effective. The same group of doctors conducted three more double-blind trials of histamine injections. A double-blind study of 90 migraine patients compared twice-weekly injections of histamine with 100 mg of oral topiramate, which is an FDA-approved treatment for migraines. These treatments were equally effective. They then compared twice-weekly injections of histamine to 500 mg of valproate, which is also an FDA-approved migraine drug in 92 migraine patients. Histamine was superior to valproate. They compared histamine to the injection of a relatively small dose of Botox (50 units, while the standard dose is155 units) in 100 patients and found them to be equally effective.

These results would be more convincing if another group confirmed these findings. When I asked the opinion of an allergy specialist in NYC, Dr. Michael Chandler he told me that the idea of histamine desensitization has been discredited and that it is not being used to treat allergies.

100 Migraine Drugs A to Z: propofol

By: Dr. Mauskop

04-06-2020

Chronic migraine, Headache medications, injections, Migraine

Propofol (Diprivan) was originally developed for general anesthesia during surgery. Smaller amounts were found to work well for “conscious sedation” to induce a semiconscious state for minor procedures such as colonoscopies.

In small doses, propofol appears to be effective for the treatment of migraines. A 2019 review of nine studies and case reports showed that “Propofol may be an effective rescue therapy for patients presenting to the ED for acute migraine, but its place in therapy based on the limited available evidence is unknown.”

Propofol was also tested for the emergency room treatment of 66 children with migraines. It was found to be as effective as the standard therapy but those give propofol had a lower rate of headache recurrence within 24 hours.

Propofol is a drug of abuse that was in part responsible for the death of Michael Jackson (it was one of several drugs found in his body). Because it is given only intravenously and is not easy to get, most of the cases of addiction reported occurred in healthcare professionals.

Propofol is administered only intravenously and at anesthetic doses it can have serious side effects such as a drop in blood pressure. However, it appears very safe for conscious sedation and is probably even safer at small doses used for migraines.

It should be considered when a patient does not respond to other intravenous therapies such as ketorolac, metoclopramide, and dihydroergotamine.

100 Migraine Drugs, A to Z: metoclopramide

By: Dr. Mauskop

19-04-2020

Headache medications, injections, Migraine

Metoclopramide (Reglan) is an anti-nausea drug that has been in use since 1979. Controlled studies have shown that metoclopramide stops not only nausea and vomiting that often accompany migraine attacks, but also relieves the pain.

The American Headache Society (AHS) and the European Federation of Neurological Societies (EFNS) guidelines on the management of adults with acute migraine recommend intravenous metoclopramide as an effective and recommended treatment in the management of acute migraine. While intravenous (IV) administration is preferred, intramuscular (IM), subcutaneous (SC) and oral routes are also effective.

These guidelines were based on many high-quality blinded studies such as one comparing 10 mg of IV metoclopramide with 600 mg of ibuprofen in which metoclopramide was clearly superior. A meta-analysis of 13 studies of intravenous metoclopramide involving 655 patients showed that “Metoclopramide is an effective treatment for migraine headache..” and that “Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments”. Another emergency room study that was done after this meta-analysis was published, compared IV metoclopramide with IV ketorolac (an NSAID pain drug) and IV valproate, (an epilepsy drug approved in a pill form for the prevention of migraines) in 330 patients. Metoclopramide was the most effective of the three.

We give IV metoclopramide in the office and prescribe it in a tablet form. However, this drug is not free of side effects. Drowsiness is one of the common side effects, but a much more unpleasant side effect is severe restlessness or akathisia. Some patients describe it as wanting to crawl out of their skin, being very restless and very uncomfortable. This side effect can be relieved by diphenhydramine (Benadryl) given IV or as a tablet. According to one study, the incidence of this side effect is 6% if the IV infusion is given over 15 minutes and 25% if given as a “push” in under a minute. We usually give it as a “push” and find that significantly fewer than 20% of patients develop this side effect.

A much more serious side effect of metoclopramide is tardive dyskinesia or involuntary movements of the mouth, face or another part of the body. The FDA warning states in part:
“The development of this condition is directly related to the length of time a patient is taking metoclopramide and the number of doses taken. Those at greatest risk include the elderly, especially older women, and people who have been on the drug for a long time. Tardive dyskinesia is rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped”. A recent review estimates that tardive dyskinesia happens in less than 1% of patients.

This very rare but devastating side effect is not likely to occur in our patients who receive this drug very infrequently, only for emergencies. However, the thought of tardive dyskinesia is always lurking in the back of our minds so we tend to use IV ondansetron (Zofran) to treat nausea. Ondansetron does not help with pain and we have to combine it with IV ketorolac (Toradol) or another drug, but it is safer.