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Alternative Therapies

Cove, a telemedicine startup provides medical care to people suffering from migraines. There are 40 million migraine sufferers in the US, only half of whom seek medical care. The other half may have mild migraines, not have access to medical care, or are under the impression that nothing can be done about their headaches. Only half of the half that go to a doctor receive a correct diagnosis of migraine. The other half, or about 10 million, are misdiagnosed as sinus, tension, or stress headaches and never receive effective treatment.

Withcove.com is website where migraine sufferers can have a neurologist evaluate their symptoms and provide an accurate diagnosis and prescribe individualized treatment. It may seem that not seeing a doctor in person would be a major obstacle, but it is not. The patient completes a questionnaire and video is used for neurological examination. The doctor evaluates the information and prescribes migraine drugs, both for the acute treatment of an attack, as well for prevention. You don’t even need to go to a pharmacy – the medicine is shipped to you. Cove also offers a variety of supplements, such as magnesium and CoQ10, which can be more effective and safer for the prevention of migraines than drugs.

My colleague at the NY Headache Center, Dr. Sara Crystal and I are helping Cove with the design of proper evaluation tools, treatment algorithms, and other aspects of care.

In addition to providing direct care, Cove is conducting some research as well. In a survey of nearly 1,000 people, a combination of Cove customers and other migraine sufferers, Cove looked at the impact of migraine on careers, to identify coping strategies, and to provide tools that make it easier to get ahead. You can read the full report, “When Migraine Gets In the Way of Careers”.

Here is a sample of the survey findings:
47% of migraine sufferers who are employed feel that migraines have held them back from advancing in their career.
30% of employed migraine sufferers said that they’ve needed to quit a job, turn down responsibilities at their current job, and/or not accept a new job because of their migraines.
38% of employed migraine sufferers have missed 5+ days of work in the past 12 months due to their migraines.

These are shocking numbers, but in line with the data known to headache specialists. Migraine is ranked globally as the seventh most disabling disease among all diseases and is the leading cause of disability among all neurological disorders. Unfortunately, research into migraines does not receive appropriate attention from the National Institutes of Health and other funding sources.

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A large study confirms previous reports of the beneficial effect of onabotulinumtoxinA (Botox) injections on depression as well as anxiety. In my two previous blog posts from 2011 and 2014 I mentioned reports of cosmetic Botox injections relieving depression but those involved a relatively small number of patients.

A study published in the Journal of Neurology, Neurosurgery, & Psychiatry under the title Effects of onabotulinumtoxinA treatment for chronic migraine on common comorbidities including depression and anxiety ,described the COMPEL trial (Chronic Migraine OnabotulinumtoxinA Prolonged Efficacy Open-Label). It was a multicenter, open-label, prospective study assessing the long-term safety and efficacy of 155 units of onabotulinumtoxinA (Botox) over nine treatments (108 weeks) in adults with chronic migraines.

OnabotulinumtoxinA treatment was associated with sustained reduction in headache days and depression and anxiety scores in the 715 patients over 108 weeks. The anxiety and depression scores were significantly reduced at all time points in patients with clinically significant symptoms of depression and/or anxiety at baseline. By week 108, 78% and 82% had clinically meaningful improvement in depression and anxiety symptoms, respectively. Sleep quality and symptoms of fatigue also improved.

In an earlier poster presentation of this data at a scientific conference the authors reported that the improvement in anxiety and depression was seen even in patients whose migraines did not improve with Botox. Even if that were true, we need a separate large study of Botox for anxiety and depression. The one study that treated patients with major depression in a double-blind, placebo-controlled trial involved only 74 patients.

In my practice, I’ve treated one young woman with severe bipolar disorder which did not respond to multiple drugs and who had a dramatic response to Botox. She has been receiving injections for over two years with sustained improvement. Another young man with depression had a very significant response as well, but has had only one treatment so far. I came to treat them accidentally – both were adopted children of my migraine patient who read about this possible effect of Botox and asked me to try it.

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Medication overuse headache (MOH) is not proven to occur from the frequent intake of triptans (Imitrex, or sumatriptan and other) or NSAIDs (ibuprofen, naproxen, and other). However, there is good evidence that caffeine (and opioid analgesics) which can help relieve an occasional migraine, can definitely make them worse if taken frequently. Caffeine withdrawal is a proven trigger of headaches, including migraines.

While we know that caffeine withdrawal causes headaches, a study just published by Harvard researchers in The American Journal of Medicine addressed an unexamined question – does drinking coffee directly triggers a migraine?

This was a rigorous prospective study of 98 adults with episodic migraine who completed electronic diaries every morning and evening for a minimum of 6 weeks. 86 participants were women and 12 were men, with mean age of 35 and the average age of onset of headaches of 16. Every day, participants reported caffeinated beverage intake, other lifestyle factors, and the timing and characteristics of each migraine headache. The researchers compared incidence of migraines on days with caffeinated beverage intake to the incidence of migraines by the same individual on days with no intake. In total, the participants reported 825 migraines during 4467 days of observation.

There was a significant association between the number of caffeinated beverages and the odds of migraine headache occurrence on that day. This association was stronger in those who normally drank 1-2 cups of coffee daily – they were more likely to get a migraine on days when they drank 3 or more cups.

Even after accounting for daily alcohol intake, stress, sleep, activity, and menstrual bleeding, 1-2 servings of caffeinated beverages were not associated with headaches on that day, but 3 or more servings were associated with higher odds of headaches, even after accounting for daily alcohol intake, stress, sleep, activity, and menstrual bleeding. The researchers also considered the possibility of reverse causation, meaning that people might have drank coffee to treat a headache, but this was also not the case.

My advice to migraine sufferers is to drink not more than 1 cup of coffee a day, and I don’t mean a Venti (24 oz) cup from Starbucks, but an 8-ounce cup of regular strength coffee. During a migraine attack having an extra cup along with your usual medication may provide additional relief.

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At the biennial International Headache Congress held last week in Dublin a group of Italian researchers presented a paper, Relationship between severity of migraine and vitamin D deficiency: a case-control study.

They examined 3 groups of subjects: 116 patients with chronic migraine, 44 patients with episodic migraine, and 100 non-headache controls. Ninety-two migraine patients had vitamin D insufficiency (borderline low levels), whereas 40 had a clear vitamin D deficiency. They found a strong inverse correlation between vitamin D levels and the severity of attacks as well as migraine-related disability.

This is only a correlational study, meaning that it does not prove that taking vitamin D will help relieve migraines. However, several neurological disorders seem to be associated with low vitamin D levels, suggesting that vitamin D is very important for the normal functioning of the nervous system. So it makes sense to keep your vitamin D levels at least in the middle of normal range.

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An alarming study entitled Association Between Migraine Headaches and Dementia in More than 7,400 Patients Followed in General Practices in the United Kingdom was just published in the Journal of Alzheimer’s Disease. The researchers found that the risk for ALzheimer’s and other dementias is increased only in women with migraines and not in men.

The first large study to discover an association between migraines and dementia was done in Taiwan. Interestingly, a follow-up study in Taiwan discovered that people who used traditional Chinese medicine (mostly herbal products Jia-Wei-Xiao-Yao-San and Yan-Hu-Suo) had lower risk of dementia than those who did not.

There is no need to panic since other studies have found no such association and there is a wide range of preventive measures that are proven effective.

Controlling ones blood pressure, blood glucose, cholesterol level, and avoiding smoking are extremely important in lowering the risk of Alzheimer’s.

The single most effective preventive measure is regular physical exercise, which is more effective than mental exercise. Engaging in mental activities, such as learning languages, solving crossword puzzles, and playing bridge (which adds the benefit of social contacts) can also help. Dancing and tai chi combine physical and social benefits. Meditation appears to be effective in preventing shrinkage of the brain, which used to be thought a normal part of aging. This was confirmed in more than one study.

In addition to Chinese herbal products mentioned above, there are several other supplements that are also less proven but are safe and may help prevent Alzheimer’s. These include vitamins B12 and D, magnesium, curcurmin, nicotinamide, and possibly other.

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Transcranial direct current stimulation (tDCS) has been definitively shown to alter brain connectivity and function. We are still enrolling patients in our double-blind study of tDCS for the prevention of migraines, so please contact us if you are interested.

A group of Iranian researchers used tDCS to treat “treatment-resistant major depression”. The results of this double-blind randomized sham-controlled trial were published in Clinical EEG and Neuroscience.

Patients with less than 50% decrease in the intensity of depression after 8 weeks of treatment with selective serotonin reuptake inhibitors (drugs like Prozac or fluoxetine, Lexapro or escitalopram, and other) were included in the trial. 16 women and 14 men were randomly allocated to an active group, which received 2-mA stimulation for 20 minutes per session, or the sham group. The Hamilton Depression Rating Scale was used to measure the severity of depression. There were statistically significant differences in the mean Hamilton scores in favor of the active treatment compared to the sham group. The difference in improvement persisted for a month after the treatment ended.

The authors’ conclusion that “tDCS is an efficient therapy for patients with resistant major depression, and the benefits would remain at least for 1 month” may be premature because of the small sample size. However, other studies have also indicated that tDCS may be effective in depression. Considering its low cost and very high safety, tDCS may be worth trying in patients with depression.

The same may apply to patients with migraines since several small studies have found this method effective. We hope that our larger study will confirm these findings. Our study differs from the previous ones and the ones for depression in that patients sue the device at home daily, rather than coming to the clinic to get the treatment. We hope that this difference will result in better outcomes.

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Many migraine sufferers have gastro-intestinal problems, such as irritable bowel syndrome, constipation, sensitivity to gluten, dairy, and other types of foods. Nausea and vomiting and gastric stasis are common symptoms of migraine. All this indicates a close relationship between the gut and migraines. Considering that we contain more bacterial cells than our own (you may want to read a fascinating book by Ed Yong, I Contain Multitudes: The Microbes Within Us and a Grander View of Life), it is not surprising that certain types of bacteria may help prevent migraines.

Bio-Kult is a probiotic that contains 14 different strains of bacteria. It was tested for the prevention of migraine headaches in a double-blind placebo-controlled trial. I mentioned the preliminary results of this study presented in 2017 at the International Headache Congress, but the final results were only recently published in Cephalalgia. The researchers enrolled 100 patients and placed 50 of them into the placebo group and 50 into the probiotic group. 43 patients on the active therapy and 36 on placebo completed the trial. Patients with both chronic and episodic migraines (15 or more headache days a month makes it chronic) were included.

After 2 month of treatment, the mean frequency of migraine attacks and their severity were significantly reduced in the probiotic group compared to the placebo group. There was also a significant reduction of the number of abortive migraine medications taken by those in the probiotic group.

This was a small study with a high dropout rate, which means that it is far from proven that this type of probiotic is effective in treating migraine headaches. However, considering the safety of this product and its reasonable cost ($21 for a month supply on Amazon.com), it is worth a try after or in addition to more proven supplements such as magnesium and CoQ10.

Although the study was conducted in Iran, Bio-Kult is manufactured in the UK, which assures good quality. It has received “The Queen’s Awards for Enterprise”.

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The role of vitamin B12 is underappreciated by many doctors. This week, The Wall Street Journal published a full-page article on vitamin B12 deficiency, which can be of great help to many of the two million readers of this newspaper. The survey quoted in the article shows that only one third of patients with this deficiency are diagnosed within a year, 22% within 1-2 years, 20% within 2-5 years 10% within 5-10 years and 14% after more than 10 years. It took several years for the author of the WSJ article to be diagnosed.

A confounding problem is that even if the doctor orders a vitamin B12 level, the widely used blood test is inaccurate. While the normal range is from 200 to 1,200 (depending on the laboratory), cases of severe deficiency have been described with levels of up to 700. You may have a good amount of vitamin B12 circulating in the blood, but it may not be getting into the cells where it is needed for the normal functioning of the nervous system, blood formation, and other functions. Many patients with a level above 200 are told by their doctors that their level is normal, but it should be at least over 400 and even better if it is above 500. We do have two additional blood tests that can confirm if the body needs additional vitamin B12 – homocysteine and methylmalonic acid levels but they are rarely utilized.

It is well worth your time to read the entire WSJ article.

I’ve written several times about the dangers of long-term treatment with PPIs, acid reducing drugs, such as Prilosec and Nexium. Among other side effects, they interfere with the absorption of vitamin B12 and other vitamins and minerals.

As far as headaches, vitamin B12 deficiency can be a contributing factor and taking vitamin B12 along with other B vitamins can relieve migraines.

Pain of facial neuralgia was found to be due to vitamin B12 deficiency in case studies of 17 patients and their pain resolved with vitamin B12 injections.

As the WSJ article suggests, many patients with neurological symptoms require regular injections rather than taking vitamin B12 pills. A couple of hundred of our patients come for monthly vitamin B12 injections, often along with an infusion of magnesium – another very common and highly underdiagnosed deficiency. It is not only migraines and other headaches that improve, but also fatigue, dizziness, and other symptoms.

Here is an old article from the Educational Materials section of our website.

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Yet 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.

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Ginger 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.

A study published in the journal of the International Headache Society, Cephalalgia examined the effect of ginger, when added to an intravenous pain medication.

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.

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To 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

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Cefaly 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).

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