Migraine | Headache NewsBlog

Galcanezumab can start to improve migraines within a day

By: Dr. Mauskop

08-03-2020

Galcanezumab (Emgality) is one of the three injectable monoclonal antibodies approved for the prevention of migraines. Pharmacological studies show that it takes up to a week for these drugs to reach their highest concentration. However, it does not mean that it takes a week for them to start helping. Many of my patients report feeling better within a day. A new study of galcanezumab indicates that such a rapid onset of action is not just due to the placebo effect.

The authors analyzed the results of two large studies of patients with episodic migraines that were submitted to the FDA to gain its approval. The first study enrolled 858 patients and the second, 915. Patients were given monthly injections of galcanezumab 120 mg (with 240 mg loading dose) or 240 mg or placebo for up to 6 months. In both studies, the onset of effect was present the day after the injection.

I do tell my patients that they might start feeling better the day after they receive their first injection (the initial dose of two 120 mg injections), but it is more likely that they will begin to improve within a week or even later. Some patients notice only minimal relief even at the end of the first month and require 2 or 3 monthly shots before any significant improvement occurs. This is true for all three injectable CGRP monoclonal antibodies.

Vyepti, the fourth drug in this family, which was just approved and will be available in a month, is given intravenously. This may result in an even faster onset of action.

Rimegepant, another very safe and effective drug receives FDA approval for the acute treatment of migraine headaches

By: Dr. Mauskop

01-03-2020

Chronic migraine, Headache medications, Migraine, New treatments

Rimegepant (NURTEC ODT) is the second gepant approved for the acute treatment of migraine headaches. It blocks the same CGRP pathway as the injectable monoclonal antibodies that are used for the prevention of migraine attacks (erenumab/Aimovig, fremanezumab/Ajovy, galcanezumab/Emgality, and eptinezumab/Vyepti). It follows the recent introduction of a similar drug that also blocks the CGRP receptor, ubrogepant (Ubrelvy).

Since there have been no head-to-head trials comparing these two gepants, it is had to say if one is better than the other. On average, they appear to be very similar, but this does not mean that they will be equally effective or cause the same side effects in a particular patient. We see this with triptans (drugs like sumatriptan, eletriptan, and other) – the top 5 show similar efficacy in trials, but some patients strongly prefer one over another.

One difference is that rimegepant is an orally disintegrating tablet and does not require water, while ubrogepant is taken with water. This makes rimegepant easier to take on the go and could be easier to take for patients with severe nausea. Another minor difference is that the dose of rimegepant is 75 mg that is taken once a day, while ubrogepant comes in 50 and 100 mg tablets and either dose can be repeated for up to 2 tablets a day. This can be both an advantage and a disadvantage. The instructions are simple for rimegepant – take one tablet once on the day you have a migraine (and the earlier you take any abortive drug the better). With ubrogepant the doctor has to decide whether to give 50 or 100 mg dose and the patient needs to be instructed to take a second dose on the same day (as soon as 2 hours after the first one) if the headache returns or does not completely resolve with the first dose. In clinical trials, this second dose did produce additional improvement.

The safety of rimegepant is as remarkable as that of ubrogepant and the preventive injectable monoclonal antibodies. Rimegepant caused nausea in 2% of patients compared with 0.4% of those on placebo and less than 1% developed a rash or temporary difficulty breathing.

100 Migraine Drugs, A to Z: nortriptyline

By: Dr. Mauskop

26-02-2020

Chronic migraine, Headache medications, Migraine

Nortriptyline (Pamelor) is a tricyclic antidepressant approved by the FDA only for the treatment of depression. However, with the introduction of SSRI family of antidepressants such as fluoxetine (Prozac) which have fewer side effects, the use of tricyclic antidepressants for depression has declined.

Tricyclic antidepressants are still in wide use, but mostly for the treatment of headaches and pain. Nortriptyline is very similar to amitriptyline (Elavil) and is thought to cause fewer and milder side effects, although this has not been proven. This could be due to the fact that amitriptyline is broken down into nortriptyline, which is the active metabolite. Amitriptyline tends to be more sedating, which can be useful in patients with insomnia.

There are no good blinded studies of nortriptyline for the prevention of migraines and they are not likely to be done. We assume it is as good as amitriptyline, although studies of amitriptyline also lack in size and scientific rigor.

There are many trials of amitriptyline and nortriptyline for various pain conditions, but they are also not up to our modern standards. Amitriptyline was approved in the US in 1961.

Besides sedation, nortriptyline can cause dry mouth, constipation, urinary retention in older patients, and other side effects. The dose to treat migraines and pain is usually lower than the dose used to treat depression. Pain and headaches sometimes respond to as little as 10 or 25 mg while for depression, the dose goes up to 100 mg and higher.

In short-term studies of major depression, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults. This is less likely to occur when treating pain, but many pain patients also experience depression.

Vyepti – Another breakthrough in the prevention of migraines

By: Dr. Mauskop

22-02-2020

Chronic migraine, Headache medications, Migraine

Eptienzumab (Vyepti) was just approved by the FDA for the preventive treatment of migraine headaches. Eptinezumab is another monoclonal antibody that blocks the effect of CGRP, a chemical released during a migraine attack. It joins erenumab (Aimovig), fremanezumab (Ajovy), and galcanezumab (Emgality), three other monoclonal antibodies approved for the preventive treatment of migraine headaches.

Eptinezumab is different from the other three drugs in that it is administered intravenously. It is given every three months by an infusion over 30 minutes. The other three drugs are self-administered subcutaneously every month, although fremaezumab can be also given every 3 months.

Eptinezumab may also have a faster onset of action because it is administered intravenously and quickly reaches its peak concentration in the blood. The other three drugs take up to a week to reach their maximum concentration. The reason for such a long delay (most drugs injected subcutaneously take less than an hour to peak) is that the monoclonal antibodies are large molecules and are distributed not by blood vessels, but the slow-moving lymphatic system. On the other hand, these are preventive therapies, so the speed of onset is less critical than for abortive drugs, such as NSAIDs, triptans, and gepants (ubrogepant, rimegepant).

Theoretically, it is possible that eptinezumab could work for patients who do not respond to the other three drugs because of a better distribution of the drug and because these drugs are not identical. About 10% of my patients report significantly better response when switched from erenumab, which was first to be approved, to either fremanezumab or galcanezumab.

We don’t know yet what the drug will cost and how well the insurance companies will pay for it. All three subcutaneous drugs cost about $650 a shot and all three manufacturers offer a one-year free trial if the insurance refuses to pay. This does not apply to patients who have Medicare or Medicaid, which do not allow free trials or discount coupons. Fortunately, more and more insurers, including the government plans, are covering these drugs, albeit with some paperwork that needs to be completed by the doctor. The cost of eptinezumab will consist of two parts – the cost of the drug and the cost of the infusion.

fMRI may offer the first accurate and objective way to diagnose migraines

By: Dr. Mauskop

18-02-2020

Migraine, Science of Migraine

A group of American and Chinese researchers reported an objective way to diagnose migraine headaches using functional magnetic resonance imaging (fMRI). The paper just published in Neurology used machine learning to examine differences between the brains of migraine sufferers, patients with chronic pain, and healthy controls.

MRI scans of migraine patients typically show normal brain structure. fMRI scans can visualize connections between different parts of the brain, or so-called connectome. The researchers discovered abnormal functional connectivity within the visual, default mode, sensorimotor, and frontal-parietal networks that allowed them to distinguish migraineurs from healthy controls with 93% sensitivity and 89% specificity. They verified the specificity of this diagnostic marker with new groups of migraineurs and patients with other chronic pain disorders (chronic low back pain and fibromyalgia) and demonstrated 78% sensitivity and 76% specificity for discriminating migraineurs from nonmigraineurs. They also found that the changes in the marker correlated with the changes in headache frequency in response to real acupuncture.

If confirmed, these findings could offer a very accurate way to diagnose migraine, rather than relying on subjective clinical description. This test could also allow for an objective way to test various new treatments. Because of the cost of fMRIs, it will be a long time before it becomes a routine clinical test. It is also possible that genetic testing and testing of blood samples for biochemical markers will lead to other accurate diagnostic tests and tests to predict responses to various therapies.

Acupuncture for migraines – worth a try

By: Dr. Mauskop

14-02-2020

Alternative Therapies, Migraine

Acupuncture has been subjected to a very large number of clinical trials for a variety of conditions, including migraine headaches. Dr. Zhang, a neurologist at Stanford and two of his colleagues have published a review of trials that compared acupuncture with standard pharmacological migraine therapy.The review included only scientifically rigorous trials that compared the efficacy of acupuncture with a standard migraine preventive medication in adult patients with a diagnosis of chronic or episodic migraine with or without aura.

Out of the 706 published reports, 7 clinical trials, with a total of 1430 participants were of high quality. Modes of acupuncture and pharmacological treatments varied from trial to trial, which made it difficult to make any sweeping conclusions. However, several of the studies showed acupuncture to be more effective than the standard pharmacological treatments for migraine prevention.

Even if acupuncture is only as effective as drugs, its safety makes it a superior choice. The major drawbacks of acupuncture are that it is time-consuming and relatively expensive when compared to generic prescription drugs. These are the reasons why I rarely perform acupuncture on my patients. If someone is interested in acupuncture, I do encourage them to try it and refer them to well-trained lower-cost non-physician providers.

100 Migraine Drugs, A to Z: nebivolol

By: Dr. Mauskop

10-02-2020

Headache medications, Migraine

Nebivolol (Bystolic) is one of the newer, third generation beta-blockers, drugs used for the treatment of high blood pressure as well as migraine headaches. In Europe, it’s been in use for over 20 years.

In addition to beta-blockade, it may have additional beneficial effects on endothelium (blood vessel lining). It may also improve glucose metabolism by improving insulin sensitivity and other functions.

Nebivolol has the advantage of having fewer side effects than other beta blockers. including lower rates of fatigue and shortness of breath.

The majority of migraine sufferers are young women, many of who have low blood pressure, which predisposes them to side effects from beta blockers.

However, in the US, nebivolol is relatively expensive ($160 for one month supply) since it is not yet available in a generic form. Many insurers will not pay for it unless the patient cannot tolerate the widely used and inexpensive beta blockers such as propranolol, metoprolol, or atenolol.

Lasmiditan – another new drug for acute treatment of migraines.

By: Dr. Mauskop

02-02-2020

Headaches, Migraine, New treatments

Lasmiditan (Rayvow) is the first (and probably the last) drug in the class of ditans. Just like the triptans (sumatriptan or Imitrex and other), it works through the serotonin system. However, it activates 5-HT_1F serotonin receptor, while triptans activate 5-HT_1Band 5-HT_1Dreceptors. This confers an advantage in that lasmiditan does not cause constriction of coronary arteries, which can happen with triptans . So patients with a history of a heart attack, angina or multiple risk factors for vascular disease who could not take triptans, now have another drug that is safe to use. The first acute migraine drug for this at-risk population, ubrogepant (Ubrelvy) became available a week ago. Lasmiditan will reach pharmacies in the next few days.

I will also prescribe lasmiditan to patients for whom triptans and ubrogepant are ineffective, partially effective, or cause side effects, which constitutes a sizable minority of my patients. .

Results of two large double-blind trials showed that 28-39% of patients achieved fast and complete elimination of migraine pain at two hours with lasmiditan as compared to 15% and 21% with placebo. 41-49% of patients achieved freedom from their most bothersome symptom of sensitivity to light, sensitivity to sound, or nausea at two hours with lasmiditan compared to 30% and 33% with placebo.

Lasmiditan is available in 50 mg and 100 mg tablets and the recommended dose is 50, 100, or 200 mg taken once a day.

Side effects were generally mild to moderate and the most frequent ones included dizziness, fatigue, tingling, drowsiness, nausea, and muscle weakness. Two driving studies showed that lasmiditan may cause significant driving impairment.

Lasmiditan is a non-narcotic medication, has low abuse potential and no evidence of physical dependence. It is a controlled substance but is in category 5, which indicates the lowest level of potential risk of abuse.

100 Migraine Drugs, A to Z: naratriptan

By: Dr. Mauskop

26-01-2020

Headache medications, Migraine

Naratriptan (Amerge, Naramig) is a triptan with a longer duration of action of 6 hours, compared to sumatriptan, rizatirptan, zolmitriptan, eletriptan, and almotriptan, which work for 2-4 hours. The seventh triptan, frovatriptan has the longest half-life of 26 hours, but its overall efficacy is not as good as than that of other triptans. These numbers of 6, 2-4 and 26 hours actually refer to drug’s half-life – the time it takes for the blood level of the drug to drop by half.

The duration of the effect is not important for most migraine sufferers because a quick-acting and highly effective drug stops the migraine process and there is no need for it to remain in the body. However, in some patients sumatriptan or another short-acting triptan may relieve symptoms for 4-6 hours and then migraine returns. Taking a second dose often works well, but not always. Those patients can benefit from taking naratriptan. Naratriptan also tends to have fewer side effects.

The longer half-life makes naratriptan better suited for “mini-prophylaxis” – taking a drug daily for several days to prevent a predictable menstrual migraine. However, sumatriptan has been also shown to work in this manner.

Just like with other triptans, naratriptan can be combined with ibuprofen or naproxen for better efficacy. Many insurers limit the number of pills they will pay for to 6 or 9, but naratriptan, along with sumatriptan and rizatriptan is one of the cheaper triptans. This allows patients to buy additional quantities, although many doctors have the mistaken belief that triptans cause medication overuse headaches and refuse to write prescriptions for more than 9 pills a month.

Light therapy with Allay lamp

By: Dr. Mauskop

19-01-2020

Alternative Therapies, Migraine

Light sensitivity is a common feature of migraine headaches and during an attack most people prefer being in the dark. According to a Harvard professor, Dr. Rami Burstein, exposure to pure green light may be better than being in complete darkness.

Dr. Burstein is one of the world’s most productive and creative headache researchers. His research has been published in such leading medical journals as Brain, Nature, Pain, Neurology, Journal of Neuroscience, and many other. This is to say that his research is of high quality and can be trusted.

I’ve known Rami for over 20 years and he never ceases to surprise with a fresh look at old phenomena that have lead him to many breakthrough discoveries. While studying light sensitivity, he decided to look at the effect of different parts of the visible light spectrum on the brain of experimental animals as well as migraine sufferers. According to his research published in Brain, white light as well as other colors of the spectrum worsen pain perception, but green light reduces pain. Blue light produces the strongest pain response and this is why some of my patients find relief from wearing orange-colored lenses that block the blue part of the spectrum.

Another paper by Burstein and his colleagues published in the Proceedings of the National Academy of Sciences suggests that exposure green light also has a positive effect on mood and autonomic nervous system functions.

Because of these findings Dr. Burstein developed a lamp that produces pure green color. A regular green-tinted bulb will not work because it does not emit a pure green light. Admixture of other colors negates the beneficial effect of the purely green light. He told me that the original prototype of the lamp cost $50,000, but eventually he and his business partners were able to reduce the price to a couple of hundred dollars. Now, you may think that he is out to make some money on his research, but that is not the case. Being a full professor at Harvard means that the university keeps the profits.

The lamp became available only a month ago and you can buy it at AllayLamp.com. Keep in mind that for green light to work, you have to turn off all other lights and computer screens and close the shades. It may take 1-2 hours to make your pain, throbbing, and other symptoms to subside. A patient I recently saw loved the idea of this lamp because whenever she gets a migraine in the summer she finds relief by sitting in her dense green garden.

100 Migraine Drugs, A to Z: naproxen

By: Dr. Mauskop

14-01-2020

Headache medications, Migraine

Naproxen (Aleve, Anaprox, Naprosyn) is a popular over-the-counter and prescription non-steroidal anti-inflammatory drug (NSAID), which is often used for the treatment of migraine headaches. A combination of naproxen with sumatriptan (Treximet) is approved by the FDA for the treatment of acute migraine attacks. Naproxen alone, while not specifically approved for the treatment of migraines, is widely considered to be an effective drug. A review of several double-blind studies confirmed this observation. It has the advantage of having longer duration of effect when compared to ibuprofen or aspirin.

Naproxen has been also studied and proven effective in a double-blind study for the prevention of migraine attacks. In another double-blind study naproxen, 550 mg taken twice a day was also effective for the prevention of menstrual migraines. It also helped relieve premenstrual pain. Naproxen is rarely used for the long-term prevention of migraines because of the risk of stomach ulcers and stomach bleeding.

NSAIDs carry a warning about the potential negative effects on the heart, but it should be of no concern to most migraine sufferers who tend to be young women with no risk factors for heart problems and who take naproxen only intermittently.

There is a myth that NSAIDs (and triptans) can cause rebound or medication overuse headaches (MOH). There is no scientific proof that this happens and in fact, when someone suffers from MOH due to caffeine-containing drugs (Excedrin, Fioricet) or opiates, naproxen is often prescribed to help withdrawal headaches.

Migraine comorbidities

By: Dr. Mauskop

05-01-2020

Migraine, Science of Migraine

If you suffer from migraines you are at a higher risk of having certain other medical problems, or comorbidities. They are not the result of having migraines, nor do those condition cause migraines. Most likely, they may have common underlying genetic, environmental, or behavioral factors. You should be aware of this link because treatment choice may be affected by the presence of these comorbidities.

Here is the list of conditions more common in migraines: anxiety, asthma, bipolar disorder, chronic pain, depression, fibromyalgia, reflux (GERD, or heartburn), irritable bowel syndrome (IBS), high cholesterol, hypertension, obesity, sleep apnea, TMJ syndrome. Having these coexisting diseases increases the risk of worsening (chronification) of migraines.

Migraine often coexists with another one or more painful conditions listed above – chronic pain (low back and other), fibromyalgia, irritable bowel syndrome, and TMJ. One plausible explanation is that chronic pain of one type leads to an increased sensitivity of brain cells. This increased sensitivity is well documented and is called wind-up phenomenon. Fortunately, many treatments can address several pain syndromes at once. These include antidepressant drugs (amitriptyline, duloxetine, and other), cognitive-behavioral therapy, exercise, and other.

One possible explanation for the coexistence of psychiatric disorders is that 40-60% of people with chronic pain have a history of physical, emotional, or sexual abuse and may suffer from posttraumatic stress disorder (PTSD). Another cause could be that they share serotonin and other neurochemical disturbances in the brain. Here too, antidepressants or certain epilepsy drugs may address both migraines and mood disorders.

Reflux (GERD) often seen in migraine sufferers could be the result of taking too many anti-inflammatory drugs such as ibuprofen, aspirin, and naproxen. Many patients will treat their heartburn with drugs such as omeprazole (Prilosec), which after prolonged use can cause multiple vitamin deficiencies, which in turn can worsen migraines and cause other symptoms.

Migraine has an inflammatory component and obesity is known to be pro-inflammatory, which could explain this connection. Diabetes drug, metformin could be a useful drug for patients who have difficulty losing weight with diet and exercise alone.