Migraine | Headache NewsBlog

100 Migraine drugs, A to Z: Alpha-lipoic acid

By: Dr. Mauskop

09-05-2018

Alpha-lipoic acid is one of the natural supplements included in this list of 100 migraine drugs. According to a study by Magis and colleagues, a daily dose of 600 mg of alpha- lipoic acid (known as thioctic acid in some countries) was significantly better than placebo in reducing the frequency of migraine attacks, headache days and pain severity. No side effects were reported in this 44-patient study. However, some of my patients have complained of upset stomach, which is not surprising since it is an acid. This was a small study and it does not conclusively prove that alpha-lipoic acid relieves migraines.

The use of this supplement is most proven in the treatment of peripheral neuropathies, which suggests that it may work for other neurological conditions such as migraine. Alpha-lipoic is being investigated as a treatment for multiple sclerosis, Alzheimer’s, diabetes, strokes and other conditions.

100 Migraine drugs, A to Z: Abobotulinumtoxin A

By: Dr. Mauskop

24-04-2018

Botox, Headache medications, Migraine

AbobotulinumtoxinA (Dysport) is a product that is very similar to OnabotulinumtoxinA (Botox), but only Botox is approved by the FDA for the treatment of chronic migraines. Botox is the oldest of the four neurotoxins that are being used for various medical and cosmetic indications.

While AbobotulinumtoxinA (Dysport) is very similar to Botox and small clinical trials suggest that it is also effective for the treatment of migraine headaches, it is not exactly the same and should not be substituted for Botox. They differ because these are not synthetic molecules, but rather complex proteins that are produced by a slightly different strain of the Clostridium botulinum bacteria. They are also processed in a different manner. Allergan, manufacturer of onabotulinumtoxinA, or Botox holds the patent for the use of a neurotoxin to treat migraines, so other companies cannot promote their products for this indication. Other toxins are approved for cosmetic and certain other medical indications.

Other toxins are a little cheaper than Botox, but I almost exclusively inject Botox because I’ve been using it for over 25 years with excellent results and very few side effects, because it has been extensively tested in thousands of migraine patients, and because it is the toxin that is usually covered by insurance companies.

Biohaven Follows Allergan in Announcing Positive Results for Rimegepant – an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine

By: Dr. Mauskop

26-03-2018

Headache medications, Migraine

Last month Allergan reported that their oral CGRP receptor antagonist, ubrogepant was safe and effective in the acute treatment of migraine attacks (see my post). Today, results of a phase 3 trial of a similar drug, rimegepant were reported. Biohaven is the company developing rimegepant, which it licensed from Bristol-Myers Squibb. Rimegepant was shown to be about as effective as ubrogepant with very few side effects, confirming that one of more of these “gepants” will make it to the market. These drugs are expected to be approved some time in 2020.

One piece of information that was not initially released by Allergan is that 5 patients on ubrogepant developed liver function abnormalities on blood tests, compared to only 1 on placebo. None of the patients taking rimogepant had liver function abnormalities. This could spell trouble for the Allergan drug, as it did for the original Merck drug, telcagepant.

Both Allergan and Biohaven have additional oral CGRP antagonists in development for the preventive treatment of migraines.

Allergan Announces Positive Results for Ubrogepant – an Oral CGRP Receptor Antagonist for the Acute Treatment of Migraine

By: Dr. Mauskop

21-03-2018

Chronic migraine, Headache medications, Migraine, New treatments

The first of the four CGRP monoclonal antibodies developed for the prevention of migraines is expected to be approved by the FDA in the next 2-3 months. The other three should be approved within a year. All four will be given by an injection (three subcutaneously and one, intravenously).

Most people prefer tablets to injections and two companies are developing three drugs with the same mechanism of action as the monoclonal antibodies (blocking CGRP), but in a tablet form. The original CGRP drug in a tablet form was developed by Merck and it was very effective for the prevention and acute treatment of migraines, but a few patients developed liver side effects. The side effects were not serious, just abnormal blood tests, which returned to normal once the drug was stopped, but nevertheless Merck stopped the development of telcagepant in 2009. This led pharma companies to shift to the development of monoclonal antibodies, which bypass the liver, but can be given only by injection.

Allergan and Biohaven are two companies that are developing oral CGRP drugs in the hope that they can achieve good efficacy without the side effects. Allergan just released the results of the first phase 3 study of ubrogepant. The study included 1327 U.S. adult patients who were given placebo, ubrogepant 50 mg or 100 mg. They treated a single migraine attack of moderate to severe headache intensity. Both doses were significantly better than placebo in achieving pain freedom at 2 hours after the initial dose. Sensitivity to light, noise, and nausea also significantly improved with the drug, but not placebo. The side effect profile of ubrogepant was similar to placebo without serious liver problems.

Results of the second phase 3 trial are expected in the first half of 2018. Allergan plans to file these results with the FDA in 2019, after which the FDA has a year to review the data and will hopefully approve the drug.

Intravenous lidocaine for pain (and headaches)

By: Dr. Mauskop

28-02-2018

Blocks, Migraine, Pain

Lidocaine is an effective local anesthetic that is injected for dental procedures, minor surgeries, as well as nerve blocks, including nerve blocks for migraines, cluster, and other types of headaches. Since it is a numbing medicine, lidocaine has been also given intravenously in the hope of relieving widespread pain or pain that does not respond to local injections. Unfortunately, it is not as effective intravenously as it is for local injections and nerve blocks for either headaches or other pain conditions.

A controlled study of intravenous lidocaine for pain was just published by Korean researchers in the Regional Anesthesia and Pain Medicine – “Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A Randomized, Double-Blind, and Placebo-Controlled Study“.

The researchers decided to examine whether pain relief from intravenous lidocaine can be sustained through repeated lidocaine infusions. This was a randomized, double-blind, placebo-controlled study of infusions of lidocaine (3 mg/kg of lidocaine administered over 1 hour) vs infusions of normal saline, given once a week for 4 consecutive weeks in patients with postherpetic neuralgia or complex regional pain syndrome (formerly called RSD, or reflex sympathetic dystrophy). The results were assessed by the change in pain score from baseline to after the fourth infusion and then again, 4 weeks later.

Forty-two patients completed this study and the percentage reduction in pain scores after the final infusion was significantly greater in the lidocaine group compared with the saline group. However, this pain reduction was not detectable at the 4-week follow-up. None of the study participants experienced serious complications from the treatment.

So, while repeated lidocaine infusions did provide effective short-term pain relief, the effect did not persist.

I have had several of my patients with severe chronic migraines respond to intravenous lidocaine, but their experience was similar – they had to get weekly infusions to maintain good relief. Because intravenous lidocaine can cause irregular heart beat (arrhythmia), cardiac monitoring is required. This makes weekly intravenous lidocaine infusions even more expensive and impractical for most pain and headache sufferers.

Botox for TMJ; the effect on clenching and grinding of teeth

By: Dr. Mauskop

24-02-2018

Botox, Migraine, TMJ

TMJ syndrome is a disorder which often coexists with migraine and tension-type headaches and is characterized by pain in the jaw joint and surrounding muscles. It is very common, but the exact cause remains unclear. In many people TMJ is a sleep disorder, which can occur in the absence of overt stress, but stress definitely plays a role in most people. Headaches in patients with traumatic brain injury can be also worsened by bruxism (clenching and grinding of teeth), while treating bruxism contributes to the relief of headaches.

Dentists usually advise patients to sleep with a custom-made bite guard, but it only reduces grinding and may not stop clenching.

The standard injection protocol for migraines includes injections into the temples (temporalis muscles), which are involved in clenching, but my 25 years of using Botox suggests that many patients get much better results if lower jaw (masseter) muscles are also injected.

A study just published in Neurology tested the safety and efficacy of onabotulinumtoxin-A (Botox) injections into those muscles (masseter and temporalis) in patients with sleep bruxism.

This study included adults with sleep bruxism which was confirmed by an overnight sleep study. The study was randomized and placebo-controlled (half received Botox and the other half, placebo), with an open-label extension (when everyone receives Botox). Participants were injected with 200 units of Botox – 60 into each masseter and 40 into each temporalis muscle or placebo (by comparison, a total of 155 units is used to treat chronic migraine headaches). They were examined 4 to 8 weeks after the initial treatment. Global impression scale and perceived change in bruxism and in pain were assessed. .

Of the 22 participants who completed the study (19 women, mean age 47 years), 13 were given Botox and 9 received placebo. Global impression, pain and bruxism favored the Botox group. Two participants who received Botox reported a cosmetic change in their smile. No other side effects were reported. I find that many patients like the cosmetic effect of injections into the lower jaw muscles – they often acquire a more rounded face, instead of a square-jawed one. On the other hand, if temporalis muscles are injected too far towards the front of the temple, it can lead to an unattractive caved-in appearance.

In addition to Botox and an oral appliance, many patients with bruxism and headaches benefit from stress reduction techniques, such as meditation, biofeedback, progressive relaxation, yoga, and other. When medications are needed, we most often prescribe muscle relaxants and antidepressants.

gammaCore for migraine

By: Dr. Mauskop

12-02-2018

Alternative Therapies, Migraine, neurostimulation

An electric stimulation device, gammaCore has received clearance from the U.S. Food and Drug Administration (FDA) as an acute treatment of pain associated with migraine in adult patients. gammaCore is a hand-held device that stimulates the vagus nerve in the neck through the skin and was developed following and based on my 2005 publication describing the use of implantable vagus nerve stimulator for refractory chronic cluster and migraine headaches. This adds to the approval gammaCore received for the acute treatment of pain associated with episodic cluster headache in adult patients in April 2017. The clearance is limited to pain of migraine, rather than migraine attacks, meaning that the device relieves pain and may not relieve other migraine symptoms, such as nausea and sensitivity to light and noise.

The FDA clearance of gammaCore for the acute treatment of pain associated with migraine was supported by the results of the multicenter, randomized, double-blind, sham-controlled trial that demonstrated that “treatment with gammaCore for the acute treatment of pain associated with migraine was superior to sham, and also enabled patients to reach pain freedom more frequently by 30, 60, and 120 minutes compared with sham treatment”. Just like with all other studies with gammaCore, the therapy was found to be well tolerated by patients.

gammaCore is also available outside of the U.S., including in Canada and the European Economic Area. The manufacturer offers a free trial of the device, which cannot be purchased, but only rented. Some insurance plans may pay for the rental.

Here are a few disclaimers and warnings from the manufacturer:

The safety and effectiveness of gammaCore (non-invasive vagus nerve stimulator) has not been established in the acute treatment of chronic Cluster Headache.
This device has not been shown to be effective for the prophylactic treatment of chronic or episodic cluster headache.
The long-term effects of the chronic use of the device have not been evaluated.
Safety and efficacy of gammaCore has not been evaluated in the following patients, and therefore is NOT indicated for:
Patients with an active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device
Patients diagnosed with narrowing of the arteries (carotid atherosclerosis)
Patients who have had surgery to cut the vagus nerve in the neck (cervical vagotomy)
Pediatric patients
Pregnant women
Patients with clinically significant hypertension, hypotension, bradycardia, or tachycardia

Patients should not use gammaCore if they:
Have a metallic device such as a stent, bone plate, or bone screw implanted at or near their neck
Are using another device at the same time (eg, TENS Unit, muscle stimulator) or any portable electronic device (eg, mobile phone)

Feverfew for migraines

By: Dr. Mauskop

28-01-2018

Alternative Therapies, Migraine

Feverfew (tanacetum parthenium) is one of the oldest herbal remedies for the treatment of migraine headaches. It was first mentioned as a treatment for inflammation 2,000 years ago. Feverfew is a member of the daisy family and all above-ground parts of the plants are safe to ingest and it is usually consumed as dried leaves or tea made of dried flowers. Besides migraine, it has been used for the treatment of fevers, rheumatoid arthritis, stomach aches, toothaches, insect bites, psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting, infertility, problems with menstruation and labor during childbirth.

We do have some scientific evidence for the effectiveness of feverfew in the prevention of migraine headaches. Here is a brief description of two of the five published trials of feverfew.

A study, Randomized double-blind placebo-controlled trial of feverfew in migraine prevention was published in the Lancet by British researchers led by JJ Murphy. 60 patients completed this study, in which half of the migraine patients received feverfew and the other half, placebo. After four months the treatment was switched (so called crossover study). Patients in the feverfew group had 4.7 fewer attacks, while placebo resulted in 3.6 fewer attacks. Global assessment of improvement was 74 vs 60. Feverfew also reduced the severity of nausea and vomiting.

Another, more rigorous study by German researchers led by HC Diener was published in Cephalalgia. It was entitled, Efficacy and safety of 6.25 mg t.i.d. feverfew CO2–extract (MIG-99) in migraine prevention – a randomized, double-blind, multicenter, placebo-controlled study.
This study enrolled 170 migraine sufferers with 89 receiving a special extract of feverfew and 81, placebo. The number of migraine attacks dropped by 1.9 in the feverfew group and by 1.3 attacks in the placebo group. The difference in the global assessment of efficacy was also statistically significant.

As far as side effects, mouth sores have been reported and, like with any herbal product, feverfew can cause upset stomach or an allergic reaction.

An issue with feverfew that applies to all herbal products is that every manufacturer processes the plant differently. In some cases, the product contains very little of active ingredients, such as parthenolides. The British researchers in the study cited above grew their own feverfew in the back yard of the hospital. An easier solution is to buy products of companies with good reputation, such as Nature’s Way, Source Naturals, and Oregon’s Wild Harvest.

Migraines can be prevented with CoQ10 supplementation

By: Dr. Mauskop

08-01-2018

Alternative Therapies, Headaches in children, Migraine

Deficiency of coenzyme Q10 (CoQ10) is the second most common deficiency in migraine sufferers after magnesium. Fully one third of migraine sufferers are deficient in CoQ10, according to a study by Dr. Andrew Hershey and his colleagues published in the journal Headache. They tested 1,550 children and adolescents and a study in such a large population tends to be very reliable. Supplementing these children with 1 to 3 mg/kg of CoQ10 produced significant improvement not only in CoQ10 levels but also in the frequency of attacks (from 19 a month to 12) and the disability (the disability score dropped from 47 to 23).

This deficiency is present in adults as well, as was shown in another study by a Swiss neurologist, Dr. Peter Sandor and his colleagues. They gave 100 mg of CoQ10 three times a day or placebo to 42 adult migraine sufferers and discovered that a 50% drop in migraine attack frequency occurred in 48% of patients on CoQ10 and only 14% of patients on placebo.

The Hershey study was done in a more logical way – determine who is deficient and give them CoQ10. If you give CoQ10 to those who need it and those who don’t, the results of the study and in practice will not be as impressive. Although CoQ10 is not expensive ($7 a month for 200 mg a day) and is very safe, why supplement to someone who does not need it? Although the blood test for CoQ10 is fairly expensive ($158 at Labcorp), it is usually covered by most insurance plans. It is important to ask your doctor what the actual blood level was because the laboratories will report as normal values between 0.37 and 2.2 (Labcorp) or 0.44 and 1.64 (Quest Diagnostics), studies have shown that the level should be at least 0.7.

As far as side effects, a few of my patients developed insomnia, possibly because CoQ10 is involved in energy generation, so I always advise taking it in the morning. While Sandor gave his patients 100 mg three times a day, in Hershey’s study the benefit appeared at lower doses. I usually recommend 100 to 200 mg (depending on body weight and how low the level is), to be taken once, in the morning.

Ignore fearmongering: triptans still do not increase the risk of strokes and heart attacks

By: Dr. Mauskop

18-12-2017

Migraine

A group of highly respected researchers at the Albert Einstein College of Medicine just published their second article in the journal Headache on the cardiovascular disease (CVD) risks in migraine sufferers. Not surprisingly, they have found that there is an increase in the CVD risk factors with increasing age – more people develop diabetes, hypertension, heart attacks, strokes, get stenting and other heart procedures as they get older.

This study concludes that, “Among people with episodic migraine in the US population, the number of women and men with relative contraindications to triptans… includes over 900,000 women and men. This includes more than half a million individuals with episodic migraine who have not had a prior cardiovascular events or procedures.” They also extensively refer to the FDA-approved label for triptans, which says that “It is strongly recommended that sumatriptan not be given to patients in whom unrecognized coronary artery disease is predicted by the presence of risk factors…”. This is because triptans can slightly constrict blood vessels, especially diseased ones (but vasoconstriction is not how triptans relieve migraines).

This is a strange conclusion considering that in the first article devoted to this large and extensive study they admit that “Serious cardiac events following triptan administration are very rare and in claims analysis, triptan use is indeed not associated with increased risk of CVD”. And the triptan label includes this statement (mentioned by the authors): “Considering the extent of use of sumatriptan in patients with migraine, the incidence of these events (drug-associated cardiac events and fatalities) is extremely low.”

The first study reported that there is a decline in the use of triptans in patients with CVD risk factors. The authors note that “It is our impression that this finding reflects a “fear-factor”; doctors may fear the onset of CV events in individuals with migraine and patients may fear the triptan label. Therefore, migraineurs that could theoretically benefit from triptans do not receive them. Nonetheless, it must be emphasized once more that triptans are not associated with the migraine/CVD relationship in populational studies; that no evidence exists to suggest increased risk of CVD in individuals with specific risk factors; and that triptans are not contraindicated in individuals without CVD but with risk factors for it.”

In the second study they inexplicably change their tune and say that “Nonvasoconstrictive acute treatments for migraine may be particularly valuable in persons of both sexes, especially men over the age of 40 and women over the age of 60. In addition, as the population ages, migraine treatments that do not constrict blood vessels may play an increasingly important role.”

What “nonvasoconstrictive acute treatments”? NSAIDs, such as ibuprofen and naproxen? Regular intake of NSAIDs, unlike that of triptans, is proven to increase the risk of CVD. Narcotics? They do not work well for most migraine sufferers and fuel the addiction epidemic. Butalbital/caffeine combination? It does not help most migraine sufferers (and was never approved for migraines) and, unlike triptans, cause medication overuse headaches.

Fortunately, patients with severe coronary artery disease and other strong contraindications for the use of triptans will soon have a safe option in a new category of migraine drugs, CGRP antagonists. They do not have any effect on blood vessels and will not have a warning label about their use in patients with CVD risk factors. However, these are very new drugs and we do not have long-term safety data that we have for triptans. Triptans have been in use for over 25 years and are sold without a prescription in most European countries.

The first group of these CGRP drugs, which will be released next year, will be given by injection for the prevention of migraines. In about 2-3 years we also hope to have CGRP drugs in a tablet form for the treatment of acute attacks. These will be expensive drugs, but their development has cost billions of dollars, so I have no quarrel with that (but insurance companies will). However, even if price was not an issue, a triptan would still be my first choice for most patients.

Breakthrough in the treatment of migraines

By: Dr. Mauskop

08-12-2017

Cluster headaches, injections, Migraine, New treatments

Two landmark studies on an entirely new type of treatment for migraines have been just published in the New England Journal of Medicine.

One of the reports describes a phase 3 trial (final phase that can lead to the FDA approval), which was conducted by Teva Pharmaceuticals using a monoclonal antibody, fremanezumab to treat patients with chronic migraine (patients with 15 or more headache days each month). The study involved 1,130 patients who were divided into three groups: one group received monthly injections (subcutaneously, i.e. under the skin) of the active medicine, another group was given an injection of the real medicine every 3 months and placebo injections monthly in between, and the third group received placebo injections every month. Patients in both groups that received real shots did much better than those given placebo. They had fewer days with headaches, used less of the abortive migraine medications, and had a lower impact of migraines on their lives. The effect of the drug lasted 3 months, which suggests that one injection every three months will be sufficient. We also hope that patients will be able to inject themselves and not have to come to doctors’ offices every month. The side effects were mostly related to the injection itself – pain, swelling, and bruising.

The second study conducted by Amgen and Novartis utilized a similar drug, erenumab (it will have the brand name of Aimovig when it becomes available in the middle of next year) to prevent episodic migraines, that is migraines that occur on fewer than 15 headache days each month. A total of 955 patients participated in this study and they were also divided into three groups: those receiving either 70 or 140 mg of medicine and a group receiving placebo. Injections were given monthly to prevent migraine attacks. Both doses of the drug resulted in significantly fewer migraine attacks and improvement in physical impairment and everyday activities. Side effects were mostly due to the injection site reactions, just like with fremanezumab.

Both fremanezumab and erenumab belong to the family of CGRP monoclonal antibodies, drugs that block a neurotransmitter CGRP which is released during a migraine attack. Two additional companies, Eli Lilly and Alder are developing similar drugs, galcanezumab and eptinezumab, which are also expected to be approved next year. Eli Lilly’s drug is also being tested for the prevention of episodic cluster headaches.

I first wrote about the CGRP drugs in a blog post in 2007, more than 10 years ago. At that point CGRP was the target of research for over 10 years, so in total, it will have taken 20 years to bring these new drugs to the market. It was even longer with triptans, such as sumatriptan (Imitrex) – it took 30 years since the discovery of the potential role of serotonin to the approval of sumatriptan. The drug development process takes not only decades of time, but also billions of dollars, which explains why new drugs are so expensive, at least in the first few years. After years of being on the market, prices of drugs tend to go down and now 90 tablets of sumatriptan can be bought for $70 at Costco, while similar branded triptan drugs used to cost $40 for a single tablet.

Vomiting from too much pot is similar to cyclic vomiting syndrome

By: Dr. Mauskop

02-12-2017

Alternative Therapies, Migraine

Excessive consumption of marijuana can lead to bouts of severe nausea and vomiting, which in medicalese is called cannabinoid hyperemesis syndrome (CHS). With many states legalizing medical and recreational marijuana, there has been an increase in ER visits and admissions to the hospital for severe vomiting. This is often misdiagnosed as cyclic vomiting syndrome (CVS), a condition which is more common in children than adults and is related to migraines. CVS, which is mentioned in a previous post, is often relieved by sumatriptan (Imitrex).

Unfortunately, people who overindulge in pot, do not realize that it is responsible for their symptoms and end up undergoing endoscopies, MRI scans and other procedures. Taking a hot shower is known to relieve pot-related vomiting, but hot shower also works for some patients with CVS, so this does not help in differentiating the two conditions. German researchers tried to find a reliable way to differentiate CHS and CVS and concluded that the only way to tell these apart is to completely stop marijuana. They do note that CHS can develop after years of using marijuana and that after marijuana use is stopped, it may take several days and up to a couple of months for symptoms to subside.

So far, we’ve prescribed medical marijuana to a couple of hundred patients with headaches, migraines, and nerve pain and have not seen such a problem. It is possible that the amount used for medicinal purposes is too small to cause CHS. The cost of medical marijuana is relatively high and could be preventing its overuse.