by Molly Rubin, a video journalist at Quartz. Quartz is a digital news site founded by the Atlantic. This is a very well done video news piece on migraines.
Read MoreMigraine
Patients suffering from migraine with aura (MA) are at a higher risk of strokes. It is not clear what leads to this problem. Elevated homocysteine level increases the risk of strokes and heart attacks and patients with MA are more likely to have this abnormality. Another possible explanation is reported in a recent study mentioned on this blog in December, This study convincingly argues that the risk of stroke is increased because of the higher incidence of a certain type of cardiac arrhythmia, atrial fibrillation in patients with MA.
The findings were a part of the Atherosclerosis Risk in Communities (ARIC) study. Among 11,592 black and white participants, 447 had MA and 1,128 MO. The risk of stroke in those whose MA began after the age of 50 was double that of those with no headaches. MA that started before 50 was not associated with stroke. MO was not associated with increased stroke regardless of the age of onset. The absolute risk for stroke in migraine with aura is 8% and migraine without aura is 4%.
To reduce the risk of strokes (whether you have migraine with aura or not) you need to keep your cholesterol under control, not smoke, exercise regularly, maintain good blood pressure and weight.
Read MoreGalcanezumab (Emgality) was the third drug in the family of CGRP monoclonal antibodies (mAbs) to become approved by the FDA for the prevention of migraines. It is more similar to fremanezumab (Ajovy) in its mechanism of action than to erenumab (Aimovig). Erenumab is an antibody that blocks the CGRP receptor, while galcanezumab and fremanezumab are antibodies that block the CGRP molecule. This may explain the fact that some patients who do not respond to one of these drugs may respond to another. Actually, even patients who do not respond or respond only partially to fremanezumab may respond to galcanezumab and the other way around. This should not be surprising since many drugs with the same mechanism of action may have different efficacy and side effects in different patients. In migraine treatment this applies to triptans, such as sumatriptan (Imitrex), rizatriptan (Maxalt), eletriptan (Relpax), and other, as well as beta blockers, such as propranolol (Inderal), atenolol (Tenormin), nebivolol (Bystolic).
Just like the other two CGRP mAbs, galcanezumab is injected monthly (although fremanezumab can be also given at a triple dose every three months). The initial dose is 240 mg, or two auto-injector pens, followed by a monthly dose of 120 mg. The main side effects are similar to the other two drugs, namely injection site reactions such as swelling, redness, and an allergic rash. Erenumab can be constipating, while the other two drugs are much less so.
The cost of all 3 drugs is the same – between $550 and $600 per monthly injection, but most insurers will pay for them if certain conditions are met. The main condition is that the patient first try and fail two oral preventive medications such as beta blockers listed above, an antidepressant such as amitriptyline (Elavil), nortriptyline (Pamelor), or duloxetine (Cymbalta), or an epilepsy drug such as topiramate (Topamax) or divalproex sodium (Depakote).
Another, more recent requirement from many insurers, is that the patient not be receiving Botox. This prohibition is very upsetting because it is not based on any science and because many patients find that together these treatments (Botox and a CGRP mAb) provide almost complete relief of their migraine attacks. Both Botox and CGRP mAbs can be life-changing on their own with dramatic relief in about 20% of patients, while another 50% of patients obtain only partial relief. This is a very rational combination because these treatments work in a totally different way and both are extremely safe with no drug interactions. The insurers justify their refusal by the fact that there are no published studies showing the safety of this combination, which is ludicrous. Some insurers, such as Cigna, go a step further in their obnoxiousness – even if a patient gets free mAb from the manufacturer or pays out of pocket, they refuse to pay for Botox. How do they know if the patient is getting a mAb? – to get prior approval for Botox we have to submit our medical notes.
All three manufacturers of mAbs, Amgen, Teva, and Eli Lilly provide up to one year of free medicine if your commercial insurance refuses to pay for it. Check each manufacturer’s website – Aimovig.com, Ajovy.com, and Emgality.com. Allergan, Botox manufacturer offers up to $700 off each quarterly treatment, so if you are paying out-of-pocket or have a high copay or deductible, check BotoxSavingsProgram.com
Read MoreYet another study shows that low vitamin D level predisposes to neurological problems. A report just published in a leading neurology journal, Neurology by British and American researchers shows that low levels of vitamin D are associated with a higher risk of delirium in hospitalized patients.
This study looked at 313,121 participants, 544 of whom were hospitalized with delirium. The researchers proved that there is genetic evidence supporting connection between vitamin D levels and delirium. They called for trials of correction of low vitamin D levels for the prevention of delirium.
It is a strange call to action because we already know from other large studies that vitamin D deficiency predisposes to several neurological problems. These include not only migraines, but also multiple sclerosis, stroke, and other major diseases Why not just make sure that nobody has a deficiency? Well, one reason is that insurance companies do not want to pay for the test because we do not have proof that correcting this deficiency will prevent these neurological problems. As we know, correlation does not mean causation. However, conducting large scale studies is very expensive and it takes many years to obtain the results. And why was a normal range for vitamin D was established if not to make sure that people are not deficient.
As I mentioned in my last post on vitamin D in 2015 everyone should have their vitamin D level checked and if you are deficient, get your level up to the middle of normal range. The normal range is 30 to 100, so below 40 is definitely not optimal.
Read MoreGinger is not only a popular spice, but a truly remarkable medicinal plant. Ginger’s proven anti-inflammatory properties may be responsible for its beneficial effects in migraine patients. Ginger may be effective for the treatment of seasickness, morning sickness of pregnancy and I recommend it for nausea of migraine as well.
This was a double-blind placebo-controlled randomized clinical trial performed in the emergency room of a general hospital in Brazil. Adults who suffered from migraines with or without aura one to six times per month were included. Half of the sixty participants were given 400 mg of ginger extract (5% active ingredient) or placebo, in addition to an intravenous drug (100 mg of ketoprofen, a drug not available in the US in an injection, but it is similar to ketorolac, or Toradol) to treat an attack of migraine. Pain severity, functional status, migraine symptoms and treatment satisfaction were recorded.
Patients treated with ginger showed significantly better pain relief after 1, 1.5 and 2 hours. Ginger also significantly improved functional status and overall satisfaction.
Another double-blind study involving 100 patients compared the efficacy of ginger with sumatriptan in the treatment of an acute migraine attack. Patient satisfaction and their willingness to continue treatment was also evaluated after 1 month following intervention. Two hours after using either drug, mean headaches severity decreased significantly. Efficacy of ginger powder and sumatriptan was similar. Adverse effects of ginger powder were less than sumatriptan. Patient satisfaction was similar in two groups.
Considering that ginger has anti-inflammatory properties, it is possible taking it daily may also prevent migraines, although no preventive trials have been conducted to date.
Read MoreGabapentin (Neurontin) is a drug that was originally developed for the treatment of epilepsy but now it is used for a wide variety of conditions except for epilepsy. It is just not strong enough to control epileptic seizures. Gabapentin can be effective for various pain syndromes, including the treatment of sciatic pain and it has an official FDA approval for the treatment of a very painful condition, postherpetic neuralgia, or shingles pain.
Several positive studies of gabapentin have been also reported for the treatment of episodic as well as chronic migraines. However, a review of all rigorous clinical trials of gabapentin for the treatment of migraine found no evidence that it really works. The authors of the review concluded that, “Since adverse events were common among the gabapentin-treated patients, it is advocated that gabapentin should not be used in routine clinical practice”. The adverse events were mostly dizziness and somnolence.
My personal experience also suggests that gabapentin is not highly effective and I do not use it “in routine clinical practice”. However, because gabapentin is proven to relieve other painful conditions and because it has a relatively benign side effect profile, I do use it in some patients with migraine, especially those with associated neck pain. It can also help patients with insomnia, although this indication is also not proven in large trials.
Gabapentin is used in doses of up to 3,600 mg a day and higher, although there have been reports of gabapentin abuse and dependence at doses above 3,000 mg a day. We usually start with 300 mg a day and slowly escalate the dose as needed and as tolerated to about 1,800 mg a day. Some patients report good relief of insomnia with 300 mg taken at night. Transition to menopause can be accompanied by temporary worsening of migriane headaches and gabapentin can also help menopausal hot flashes (and sleep) at a dose of 900 mg a day.
Read MoreTo be eligible for this study you have to live in NYC or its suburbs and cannot be currently receiving Botox or a CGRP monoclonal antibody, such as Aimovig, Ajovy or Emgality.
PARTICIPATE IN MIGRAINE RESEARCH
A RANDOMIZED SHAM-CONTROLLED STUDY OF HOME-DELIVERED NON-INVASIVE NEUROSTIMULATION FOR MIGRAINE
• If you have frequent headaches (on 4 days or more/month) you may be eligible to enroll in a study of non-invasive neurostimulation aiming to reduce migraines.
• Neurostimulation provides stimulation of the nerves in the human body. Frequently used neurostimulation methods are for example, acupressure, acupuncture or TENS.
• This study uses a new neurostimulation method, tDCS. tDCS is a battery-powered device that delivers stimulation via two sponge pockets placed to a simple headband. Study participants will be assigned either to a group receiving active tDCS or to a control group receiving placebo tDCS.
If you are interested in more information about the study, please call the study personnel at 212-794-3550 or 212-440-1954 or email DrMauskop@nyheadache.com
Read MoreCefaly is a transcutaneous electrical nerve stimulation (TENS) device designed to treat migraine headaches by stimulating supraorbital nerves. The device was cleared by the FDA in 2014 for both acute and preventive treatment of migraine headaches. The preventive indication was based on a double-blind trial involving only 67 patients, while the use of Cefaly for acute migraines was based only on an open-label trial. A study recently published in Cephalalgia examined the efficacy of this device for acute treatment of migraines in a double-blind trial of 106 patients.
The trial confirmed that Cefaly is indeed effective for abortive therapy of migraine attacks. For prevention, it is recommended to use the device for 20 minutes every day, while to treat an acute attack the device should be used for an hour. The primary outcome measure was the mean change in pain intensity at 1 hour compared to baseline. This primary outcome measure was significantly more reduced in the stimulation group compared to the sham group: 60% versus 30% reduction. No serious adverse events were reported and five minor adverse events occurred in the stimulation group. I’ve had one or two patients report that the device actually triggered a migraine, but this can also happen with any oral migraine drug.
The main reason I offer Cefaly before any other device (eNeura TMS or gammaCore) is that it is the most affordable. The price has gone up since it’s introduction and ranges from $350 to $500, however the manufacturer offers a 60-day return policy. This is long enough to see if it is effective. Cefaly is sold only with a doctor’s prescription, which is uploaded to the Cefaly website (Cefaly.us for US patients and Cefaly.com for the rest of the world).
Read MoreSeveral older reports have suggested an association between dry eye disease (DED) and migraine headaches. Researchers at the Univercity of North Carolina at Chapel Hill just published a large and convincing study confirming this comorbidity.
This was a retrospective study which included 72,969 patients older than 18 years seen over a period of 10 years. The study included 41,764 men and 31,205 women. Of these, 5,352 patients (7.3%) were diagnosed to have migraine headaches and 9,638 (13.2%) had the diagnosis of DED. The odds of having DED and migraine headaches was 1.4 times higher than that of patients without migraine headaches. This association was true for men and women older than 65 and women of all ages. Older age and female sex are both risk factors for the development of DED, probably due to hormonal and age-related changes.
The incidence of migraines and DED in the general population are reversed – about 12% suffer from migraines and 7% from DED, which is probably due to the fact that the study included only patients see at ophthalmology clinics.
The authors conclude that patients with migraine headaches are more likely to have comorbid DED compared with the general population, but this association may not reflect cause and effect. Both conditions do share inflammation as one of the underlying processes.
It is very likely that the eye discomfort from DED can be making migraines more frequent and severe. The diagnosis of DED should be considered in all migraine sufferers, especially in those with difficult to control attacks because effective treatment of DED could lead to an improvement in migraines.
Read MoreFrovatriptan (Frova) is one of seven drugs in the family of triptans, drugs used to abort a migraine attack. The first drug to receive approval in 1992 was sumatriptan (Imitrex) in an injection form, followed by tablets and nasal spray. Other drugs in this category are rizatriptan (Maxalt), zolmitriptan (Zomig), naratriptan (Amerge), almotriptan (Axert), and eletriptan (Relpax).
Frovatriptan is probably the least effective triptan and this is in part because it is the longest-lasting triptan and takes the longest to start working. Its half-life is 26 hours, which means that the body clears out half of it in that period of time. The half-life of sumatriptan, rizatriptan and zolmitriptan is 2 to 3 hours, almotriptan – 3 to 4 hours, eletriptan – 4 hours, and naratriptan – 6 hours.
When speed of onset is not crucial, which is when migraine develops slowly over a few hours, frovatriptan has the advantage of longer effect. However, if it does not provide good relief to begin with, the amount of time it stays in the body is irrelevant. Short-acting triptans work quickly and stop the migraine attack.
Frovatriptan is sometimes used for “mini-prophylaxis” of menstrual migraines – it is taken the day before the expected menstrual migraine and throughout the period. However, other triptans, including sumatriptan and naratriptan can be also effective in preventing predictable migraines, such as those occurring with periods, physical exertion or sexual activity.
Another disadvantage of frovatriptan is that it is expensive even in a generic form – $20 a pill. The triptans that only recently lost patent protection, such as frovatriptan and eletriptan have fewer generic copies and their prices are still high.
Read MoreA study just published in Neurology by the MEGASTROKE project of the International Stroke Genetics Consortium found that “genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke…” It is an open access article, so you can download the full text. The study looked at 34,217 cases of strokes and 404,630 noncases, which makes the data highly reliable.
Here are some quotes (some modified) from the paper.
Several observational prospective studies have reported that low circulating magnesium concentrations and low magnesium intake are associated with increased risk of stroke. In the Nurses’ Health Study, low plasma magnesium concentrations were associated with an approximately 70% to 80% increased risk of embolic and thrombotic stroke.
Magnesium may in part reduce the risk of cardioembolic stroke through its antiarrhythmic effects and via atrial fibrillation. Low serum magnesium concentrations are associated with increased risk of atrial fibrillation, which is a strong risk factor for cardioembolic stroke. (My recent post mentioned that the increased risk of strokes in patients with migraines with aura is possibly related to the higher incidence of atrial fibrillation) Two of the magnesium-associated SNPs (genetic variants) were significantly associated with atrial fibrillation, with higher serum magnesium concentrations being associated with lower risk of atrial fibrillation.
Magnesium also has anticoagulant and antiplatelet properties (platelet aggregation is also implicated in migraine). Magnesium is considered to be nature’s calcium blocker as it suppresses many of the physiologic actions of calcium. For example, calcium promotes blood coagulation, whereas magnesium suppresses blood clotting and thrombus formation and reduces platelet aggregation. Antithrombotic effects may lead to reduction in risk of both cardioembolic and large artery stroke.
Other possible mechanisms whereby high serum magnesium concentrations may reduce ischemic stroke risk include improvement of endothelial function and reduction in blood pressure, atherosclerotic calcification, arterial stiffness, oxidative stress, fasting glucose concentration, insulin resistance, and risk of type 2 diabetes. Some of those beneficial e?ects may also lead to a reduction in small vessel stroke, which was not observed in this study.
Magnesium also reduces the size of a hemorrhagic stroke (bleeding into the brain), according a another recent study.
Magnesium has been my main area of research and because I never tire of promoting the role of magnesium in the treatment of migraines some colleagues call me Dr. Magnesium. The evidence is overwhelming – many studies have shown that magnesium deficiency is common in migraine sufferers and that taking magnesium can help. The American Academy of Neurology and the American Headache Society guidelines for the treatment of migraines include magnesium, but it is still underappreciated and underutilized. This is in part because there have been no large-scale (i.e. expensive) trials of magnesium which are done by pharmaceutical companies for new drugs. Another reason is that the trials that have been conducted supplemented migraine patient regardless of their magnesium status – both deficient and non-deficient patients were given magnesium, thus obscuring the great benefit obtained by the deficient cohort.
As mentioned in several previous posts, magnesium also helps asthma, palpitations, feeling cold or having cold hands and feet, muscle twitching, cramps or diffuse muscle aches (fibromyalgia), premenstrual symptoms (PMS), brain fog, and many other symptoms. If you have any of these symptoms you may want to have a blood test for magnesium. And even if you don’t have symptoms, the next time you have any kind of a routine blood test, ask your doctor to add a test for “RBC magnesium”, which is more accurate than the usual “serum magnesium”.
If you have any of the above symptoms, you can also just start taking 400 mg of magnesium glycinate, which is the daily recommended allowance for magnesium. If oral magnesium does not help and the RBC magnesium level is low we usually give monthly infusions of magnesium. They take 10 minutes to do, have no side effects and are covered by most insurance plans.
Read MoreFremanezumab (Ajovy) is one of the three drugs in the family of CGRP monoclonal antibodies that have been approved for the prevention of migraine headaches.
Fremanezumab was approved by the FDA last September. After trying erenumab (Aimovig), which was approved first, I also injected myself with Ajovy monthly for two months. My migraine headaches do not cause any disability, so I did it to see if I can reduce my attacks from triggers such as red wine, which it did, and to reassure my patients about the relative safety of these drugs.
Over the years I’ve tried Botox a couple of times and a few other treatments, but not drugs such as topiramate (Topamax) or divalproex sodium (Depakote), which I rarely prescribe to my patients because of their potential to cause serious side effects. Fortunately, my occasional migraines have always been easily controlled with sumatriptan (Imitrex), so I do not need any preventive therapies.
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