New treatments | Headache NewsBlog

A new class of migraine drugs is on the horizon

By: Dr. Mauskop

03-07-2015

For years researchers have tried to find ways to block various chemicals (neurotransmitters) released during a migraine attack, including serotonin, CGRP, nitric oxide, substance P, glutamate, and other. Triptans (such as IMitrex or sumatriptan), the first “designer” drugs for migraine, which were developed over 20 years ago, bind to a very specific subtype of serotonin receptor and are very effective in stopping a migraine attack.

A very promising new type of migraine medications is being developed by at least four different companies – Alder, Amgen, Eli Lily, and Teva. These drugs are monoclonal antibodies against the CGRP molecule or the CGRP receptor. CGRP (calcitonin gene-related peptide) is widely distributed in the body and is involved in regulating blood vessel opening and in the function of the nervous system. All four companies developing these drugs recently presented the results of their phase II clinical trials and the data looks very promising. The antibody tightly binds to its target (CGRP molecule or receptor) with the effect lasting a month, or in case of the Alder drug, up to 6 months. The Alder drug is given every six months intravenously, while the other three, are given every month by an injection into the muscle.

All four drugs appear to be very effective in preventing migraine attacks when compared to a placebo injection. And fortunately, at least so far, they all look very safe. However, in phase II trials only a couple of hundred patients are treated and we need to await the results of the larger and more definitive phase III trials to confirm the safety and efficacy of this new group of medications. This means that the earliest we will see these drugs approved by the FDA is in about 3 years.

It is possible that these drugs will be effective not only for the prevention of migraines, but also for stopping an acute migraine attack.

An update on closing PFO (a heart defect) to treat migraines

By: Dr. Mauskop

24-06-2015

Migraine, New treatments

An opening between the left and the right side of the heart, called patent foramen ovale (PFO), is found in 25% of the general population. It has been found to be more common in people who suffer from migraines. A large PFOs can cause shortness of breath, heart failure, and strokes and they are usually closed surgically. Several companies developed a device to close this opening without open heart surgery, but rather by inserting an umbrella-like device through a vein in the groin.

The manufacturers of these devices have conducted clinical trials in the hope of preventing migraines by closing the PFO. The results so far have been mixed with some studies showing improvement in migraines and some showing no benefit. A study just presented at the annual meeting of the American Headache Society by Dr. Andrew Charles of UCLA and his colleagues reported on one such trial. This study was blinded, with 107 patients having a sham procedure (the catheter was inserted into the groin vein, but the PFO was not closed) and 123 having their PFO closed. Overall, there was a significant reduction in headache days in the closure group (-3.4 days) compared with the sham group (-2.0 days), however there was no difference in the primary efficacy endpoint of the number of patients with 50% or more reduction in migraine attacks.

A subset of patients did particularly well compared to the sham group – patients who had migraine aura with the majority of their migraine attacks. A significant reduction in migraine days was present in half of patients with aura compared with a quarter in the control group. About 11% (8 out of 74 patients) of those who had migraine with aura had complete elimination of migraine attacks, while this happened to only 1.5% (1 out of 68 patients) in the sham group with auras.

This study suggests that patients who have auras with the majority of their migraine attacks and whose migraines are difficult to control should undergo an echocardiogram to test for the possible presence of a PFO. If PFO is present, it may be reasonable to consider seeing an interventional cardiologist to close the PFO. This is a relatively safe procedure if done by an experienced doctor and that is a very important if. Pick a doctor who has done a hundred or more of these procedures.

Topical cream for migraine

By: Dr. Mauskop

05-05-2015

Alternative Therapies, Migraine, New treatments

A topical cream seems to be effective in treating migraine headaches. Achelios Therapeutics announced results from a Phase IIa placebo-controlled clinical trial in moderate and severe migraine sufferers treated with Topofen, the company’s proprietary topical anti-migraine therapy. This is a well-known non-steroidal anti-inflammatory drug (NSAID) ketoprofen, which is applied to the face and seems to provide relief for patients suffering from acute migraine.

The results of the clinical trial were presented at the American Academy of Neurology annual meeting in Washington, D.C. Surprisingly, this study showed that it may be possible to relieve severe migraine with a topical application to facial nerve endings. Topical application avoids potentially serious side effects of NSAIDs, such as stomach bleeding and ulcers. The randomized, crossover, double-blind, placebo-controlled study involved only 48 adults with a history of episodic migraine with and without aura. Of the severe migraine patients, 77 percent experienced relief of pain and migraine-associated symptoms and 45 percent had sustained pain relief from two to 24 hours compared to 15 percent on placebo. Also, 50 percent of patients who treated their severe pain with Topofen were pain free at 24 hours compared to 25 percent of placebo-treated patients. Some patients experienced application-site irritation, which was mild or moderate in severity. That was the only reported side effect, which resolved quickly.

Such a small study does not prove that this treatment is in fact effective. A typical drug trial required for an FDA approval usually involves hundreds of patients. However, you do not need to wait for this cream to appear on the market because there are creams containing an NSAID already available by prescription (Voltaren Gel) and over-the-counter (Aspercreme). It is possible that the cream tested in the study may be better because it is a different NSAID, but Voltaren Gel is already approved and you can ask your doctor for a prescription. It is possible that insurance companies will not pay for it since it is not approved for migraines. A tube of Voltaren Gel will cost you about $55 (go to GoodRx.com to get the lowest price).

Treating chronic migraines with Botox is cost-effective

By: Dr. Mauskop

22-12-2014

Botox, New treatments

Cost is the only major issue with Botox injections, which is the only FDA-approved treatment for chronic migraines and which is now covered by almost all insurance companies. It is very safe and highly effective, relieving headaches in 70% of migraine sufferers. A study just published in the journal Headache suggests that Botox may be not only clinically effective, but also cost-effective.

Researchers from the Renown Neurosciences Institute in Reno, Nevada analyzed data from 230 chronic migraine sufferers who did not respond to two or more prophylactic drugs and were given Botox injections. Botox was given twice, three months apart. Compared with the 6 months before Botox, there were 55% fewer emergency room visits, 59% fewer urgent care visits, and 57% fewer admissions to the hospital. In those 6 months the savings amounted to half of the cost of Botox treatments. Considering that improvement tends to get more pronounced with each subsequent Botox treatment, it is very likely that the costs savings would grow with additional treatments.

Obviously, besides saving money, Botox provides a significant improvement in the quality of people’s lives, which is much harder to measure. At our Center we give Botox to more than a quarter of our patients and see a dramatic improvement in the majority. Botox is not only much more effective for chronic migraines, but it is also much safer than any oral medication.

More on migraine surgery

By: Dr. Mauskop

14-11-2014

Chronic migraine, New treatments

A new report by Drs. Gfrerer, Maman and their colleagues at the Massachusetts General Hospital in Boston entitled Non-Endoscopic Deactivation of Nerve Triggers in Migraine Headache Patients: Surgical Technique and Outcomes was recently published in the journal Plastic & Reconstructive Surgery. Surgery for refractory migraine headaches was developed by Dr. Bahman Guyuron and others and was reported to benefit between 68 and 95% patients. This surgery involves cutting or freeing up nerves in the scalp that appear to be responsible for triggering migraines. Some surgeons use a laparascopic technique, which involves making only a few small incisions while others do this surgery through conventional incisions. The authors of this new study argue that endoscopic techniques may not be appropriate in many cases since some surgeons have little experience or limited access to the endoscope and in some patients this technique is not practical because the nerves could run in an unusual pattern, which would make them hard to find through a small incision.

This study involved 43 consecutive procedures in 35 patients. All patients completed questionnaires before and 12 months after surgery. The overall positive response rate was 91%. Total elimination of migraine headaches was reported in 51%, greater than 80% resolution of symptoms in 21%, and 28% had resolution between 50-80%. No improvement was reported after 9% of procedures. There were no major adverse events.

The authors concluded that non-endoscopic surgery was safe and effective treatment in select migraine headache patients.

Most headache experts agree that until proven effective in large controlled studies, surgery should be done only as a part of such a large controlled trial. Just like with previous studies of surgery for migraines, this was a small and not a rigorously controlled trial. Placebo response to surgical procedures is usually very high, however it is rarely 90% and the effect rarely lasts 12 months, as it did in this study. Considering these facts, as well as that this study was done at a reputable institution and that this group consisted of refractory patients (those who did not respond to conventional therapy, including Botox), surgery may in fact offer some real benefits to a small group of patients. We need larger and better controlled trials to figure out if that is indeed the case and what type of patients are the best candidates for surgery.

Stem cells for headaches

By: Dr. Mauskop

16-10-2014

Alternative Therapies, New treatments, Science of Migraine

The first time I heard of the potential benefit of stem cells for migraine headaches was last year from one of my patients. This 55-year-old woman had been having some improvement from intravenous magnesium and nerve blocks, while Botox was ineffective. However, she reported a dramatic improvement in her headaches after receiving an intravenous infusion of stem cells in Panama. The stem cells were obtained from a donated umbilical cord.

Stem cell research has been controversial because most of the early research used stem cells obtained from an aborted fetus. Since then, stem cells have been obtained from the bone marrow, umbilical cord, placenta, and artificial fertilization. Another rich source of stem cells is body’s fat tissue. Most of the stem cell procedures are not yet approved in the US. The main concern is that when you obtain stem cells from another person’s umbilical cord or placenta, there is a risk of transmitting an infection. There are relatively few stem cells in the bone marrow, placenta or the umbilical cord, which means that after isolating them, they need to be grown in a petri dish. This process involves adding various chemicals, which may not be safe, according to the FDA.

A group of doctors in Australia recently reported relief of migraines using stem cells from patients’ own fat. These doctors did not grow these cells, but infused them intravenously right after separating them from fat. The infused cells were not only stem cells, but so called stromal vascular fraction, which also includes cells that surround blood vessels. These four patients were given stem cell treatment for osteoarthritis and not migraines, but they noticed that their migraines and tension-type headaches improved.

Four women with long histories of chronic migraine or chronic tension-type headaches were given an infusion of cells isolated from fat, which was obtained by liposuction. Two of the four patients, aged 40 and 36 years, stopped having migraines after 1 month, for a period of 12 to 18 months. The third patient, aged 43 years, had a significant decrease in the frequency and severity of migraines with only seven migraines over 18 months. The fourth patient, aged 44 years, obtained a temporary decrease for a period of a month and was retreated 18 months later and was still free of migraines at the time the report was submitted one month later.

This case series is the first published evidence of the possible efficacy of stromal vascular fraction in the treatment of migraine and tension-type headaches.

It is not very surprising that stem cells can improve migraine headaches because stem cells are tested as a treatment for a variety of inflammatory diseases, such as multiple sclerosis, arthritis, and colitis. Inflammation is proven to be present during a migraine attack and this inflammation may attract stem cells. Many experts believe that stem cells may work for MS or other neurological disorders not by becoming brain cells, but by stimulating body’s own repair mechanisms.

Eye drops to treat an acute migraine

By: Dr. Mauskop

07-10-2014

Headache medications, New treatments

Beta blockers (Inderal or propranolol and similar drugs) are used for the preventive treatment of migraine headaches. Over the years, a few patients have told me that they take a beta blocker only when they have an attack of migraine with very good results. A report published in Missouri Medicine describes seven patients whose acute migraine headache went away with eye drops containing a beta blocker. These eye drops are used for the treatment of glaucoma. The authors argue that having medicine go into the eye allows it to get absorbed quickly into the blood stream. This is certainly true, but my first thought was that there is too little medicine in eye drops to produce an effect outside the eye. However, beta blocker eye drops can worsen asthma, lower the blood pressure and slow the heart rate, suggesting that the amount of medicine in eye drops is sufficient to cause effects beyond the eye. Oral beta blockers used daily for the preventive treatment of migraines are also contraindicated in those medical conditions. Considering that eye drops are probably safer than many oral medications used to treat an acute migraine attack and that they most likely work faster, this treatment is worth trying.

Peripheral nerve blocks for an acute migraine

By: Dr. Mauskop

15-09-2014

Alternative Therapies, neurostimulation, New treatments

Peripheral nerve blocks can be very effective in stopping a severe migraine attack. We utilize them when a patient does not respond to oral or injected medications or when medications are contraindicated because of a coexisting disease or pregnancy.

Dr. Jessica Ailani and her colleagues at the Georgetown University in Washington, D.C. presented their experience with nerve blocks at the last annual meeting of the American Headache Society in Los Angeles. The study included 164 patients. Most patients received occipital and trigeminal nerve blocks using lidocaine or a similar local anesthetic.

Most patients were satisfied with the results, which lasted from several days up to 2 weeks. Only a small number of participants experienced side effects such as soreness at the site of injections, nausea and vomiting, and head and neck pain.

Dr. Ailani noted that more than 71% of patients rated their pain as 4 to 8 out of 10 before treatment with a nerve block. After a nerve block, nearly half (47.2%) said the pain had reduced to 1 out of 10.

“This is a very well-tolerated procedure and patients are very satisfied with the procedure,” said Dr. Ailani.

Nerve blocks can help keeps headache sufferers out of the emergency room and provide an alternative to systemic drugs, that is drugs that are injected or ingested. Systemic drugs affect the entire body while nerve blocks exert only local effects (unless one is allergic to local anesthetics).

Dr. Robert Kaniecki, a headache specialist in Pittsburgh uses nerve blocks for the prevention of chronic migraine headaches. He administers them into the same areas where Botox is injected. He finds that for some of his patients nerve blocks given every 12 weeks can be as effective as Botox. It is possible that such patients have milder migraines since the effect of nerve blocks lasts a very short time (lidocaine leaves the body after 4 hours or so) compared with the effect of Botox which lasts 3 months. Unlike Botox injections, nerve blocks have not been subjected to a rigorous scientific study comparing them to placebo (saline) injections.

Predicting response to Botox in chronic migraine.

By: Dr. Mauskop

08-07-2014

Botox, Chronic migraine, New treatments

Botox is a very effective treatment for chronic migraines and possibly other types of headaches and pain. However, Botox is an expensive and somewhat unpleasant treatment. Even though Botox helps a high percentage of patients (about 70%) it would be useful if we could predict who is going to respond and who is not.

One of the predictors seems to be the directionality of pain. That is, if patients with migraine who have constricting (imploding) pain or pain localized to the eye seem to respond better than those who have pain that seems to be pushing from inside out (exploding). This is not a very reliable predictor because some people have difficulty categorizing their pain in that way and because even if they do describe it clearly one way or another, this predictor is far from 100% accurate.

In a study just published in the journal Headache a group of Spanish neurologists claim that they have found a predictor with 95% accuracy. They measured blood levels of calcitonin gene-related peptide (CGRP) and found that those with levels of CGRP above a certain number were 28 times more likely to respond to Botox than those with levels below that level.

CGRP has been shown to be very involved in the process of migraine and several drugs and antibodies which block the CGRP receptor appear to be very promising (see my recent blog post on such antibodies). So, it is not very surprising that this correlation between the response to Botox and blood level of CGRP was found. However, this finding needs to be confirmed in a larger group of patients (this study involved 81 patients) and this test needs to become available commercially since now it can be done only in research laboratories.

Another delay for a long awaited drug

By: Dr. Mauskop

01-07-2014

New treatments

The introduction of Levadex has been delayed again, this time for a year. It seems like deja vu all over again – I wrote the same thing on this blog in April of last year. Levadex, which the manufacturer (Allergan) just renamed as Semprana, is an inhaler containing DHE. DHE, or dihydroergotamine is one of the most effective injectable drugs for migraine. It should be even better in an inhaled form because it works faster and causes much less nausea than the injection. The FDA is again delaying the launch because of manufacturing problems. Apparently, the particle size of the drug when it comes out of the inhaler is not uniform enough. Many patients are unhappy, but I am sure that the Allergan is very unhappy too since they spent almost a billion dollars to acquire this drug from a small company that developed it.

LSD, ‘shrooms, psilocybin for cluster headaches

By: Dr. Mauskop

27-05-2014

Alternative Therapies, Cluster headaches, New treatments

Cluster headache patients have been coming to our office in increasing numbers in the past few weeks. We seem to be in a cluster season – many patients with cluster headaches come within the same month or two and then, for several months we see very few cluster patients. Many cluster headache sufferers ask about the efficacy of LSD, hallucinogenic mushrooms and seeds.

The use of hallucinogens for cluster headaches was first reported by a Scottish man in 1998. He started using LSD for recreation and for the first time in many years had a year without cluster headaches. The first report in scientific literature appeared in 2006 in the journal Neurology. Dr. Sewell and his colleagues surveyed 53 cluster headache sufferers, of whom 21 had chronic cluster headaches. Half of those who tried LSD reported complete relief.

Researchers are trying to study a version of LSD (brominated LSD) that does not cause hallucinations. This form of LSD was reported in the journal Cephalalgia to stop cluster attacks in all five patients it was given to. It is not clear if any additional studies are underway, but one American doctor, John Halpern is trying to bring this product to the market in the US.

Trying to obtain LSD or hallucinogenic mushrooms carries legal risks, including incarceration. According to Dr. McGeeney, who is an Assistant Professor at Boston University School of Medicine, it is legal to buy, cultivate, and sell seeds of certain hallucinogenic plants, such as Rivea Corymbosa, Hawaiian baby woodrose, and certain strains of morning glory seeds. However, it is not legal to ingest them.

The bottom line is that I urge my patients not to try hallucinogens because their safety has not been established. This is especially true for illicit products, which may contain additional toxic substances.

Fortunately, we do not need to resort to these agent because we have such a variety of safer and legal products. These include preventive medications, such as verapamil in high doses, topiramate, lithium, and for chronic cluster headaches, Botox injections. None of these drugs are approved by the FDA and are not likely to be approved because this is a relatively rare condition, which makes performing large studies very difficult. The only FDA-approved drug for cluster headaches is an abortive drug, injectable sumatriptan (Imitrex).

New migraine drugs in the pipeline

By: Dr. Mauskop

26-05-2014

New treatments

Two new migraine drugs are about to be released on the market. They were mentioned in this blog in their earlier stages of development. Another two drugs are more interesting, but are several years away from becoming available (if at all).

Zecuity is a patch that delivers sumatriptan (active ingredient in Imitrex) through the skin. The patch contains a small battery and the electric current it generates helps the medicine penetrate through the skin. The patch is particularly useful when migraine is accompanied by nausea and vomiting. The main side effect of the patch, compared to the tablet, is that it causes irritation of the skin in one third of patients. This product was already approved by the FDA and will be soon available in pharmacies from its manufacturer, Teva Pharmaceuticals.

Levadex is a drug inhaled into the lungs using a device similar to those used for asthma drugs. It contains dihydroergotamine – a very old and very effective injectable drug. Dihydroergotamine does not work well in a nasal spray (Migranal) or when taken by mouth. Levadex causes less side effects, such as nausea, than the injection of this drug. The main target population for this drug is also migraine sufferers who experience nausea and vomiting and for whom tablets do not work. Because it works very fast it may be also very effective for those whose headache starts and escalates to a severe intensity very quickly, which includes not only migraine, but also cluster headache sufferers. Levadex is manufactured by Allergan, the company that also makes Botox. It should be available in the next few months.

Lasmitidan is a new drug being developed by CoLucid. It is in phase III trials, which is the final phase, which if successful, can lead to the FDA approval. Lasmitidan is a new type of drug – it targets a specific serotonin receptor subtype – 1F, while triptans (sumatriptan, rizatriptan, and other) target 1B and 1D serotonin receptors. It may have the advantage of not constricting arteries at all and may be allowed in patients with coronary artery disease. Triptans are contraidicated in such patients.

Merck is developing a drug, which does not have a name yet, only a number – MK-1602. It is a CGRP receptor antagonist – a blocker of a neurotransmitter in the brain that is involved in migraine origination. It is in phase II trials. MK-1602 also has the advantage of not constricting arteries. At least two other companies are developing CGRP antibodies (different from CGRP antagonists) and they were mentioned in a recent post here.

A new class of migraine drugs is on the horizon

An update on closing PFO (a heart defect) to treat migraines

Topical cream for migraine

Treating chronic migraines with Botox is cost-effective

More on migraine surgery

Stem cells for headaches

Eye drops to treat an acute migraine

Peripheral nerve blocks for an acute migraine

Predicting response to Botox in chronic migraine.

Another delay for a long awaited drug

LSD, ‘shrooms, psilocybin for cluster headaches

New migraine drugs in the pipeline

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