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Headaches

Trigeminal neuralgia (TN) is an extremely painful and often debilitating condition. Many people respond to the standard therapy with epilepsy drugs such as carbamazepine (Tegretol) or oxcarbazepine (Trileptal). Botox injections can be helpful as well. A significant minority of patients, however, do not respond to these treatments and sometimes require brain surgery.

Fortunately, we have a new class of drugs that has allowed some of my patients to avoid having an operation. These drugs are CGRP monoclonal antibodies (mAbs). They have been approved by the FDA only for the prevention of migraine headaches, so their use for TN is considered to be “off-label”.

The first case series was reported in 2019 by the Cleveland Clinic doctors. They found that six out of eight TN patients had a good response to erenumab (Aimovig).

A group of Israeli physicians published another case series in the current issue of Neurology. They found that nine out of ten TN patients obtained very good relief from erenumab.

Erenumab was the first CGRP mAb. It was approved in May of 2018. Another two, galcanezumab (Emgality) and fremanezumab (Ajovy) were approved about six months later. These are given by a monthly subcutaneous injection. About a year ago, an intravenous CGRP mAb, eptinezumab (Vyepti) was also approved. These four drugs are very similar. However, some patients find one to be more effective than others. I’ve found this to be true not only in migraine patients but also in those with TN. Erenumab is slightly different in its mechanism of action and it is the only one that has a warning about the potential for causing severe constipation and increased blood pressure. Since TN patients tend to be older and more prone to these side effects, I prefer galcanezumab or fremanezumab. Unlike eptinezumab, they can be self-administered.

Off-label use is totally legitimate. However, insurance companies are not likely to pay for an expensive drug that is not explicitly approved by the FDA for a specific indication. And these drugs are not cheap – about $600 to $700 for each monthly shot. Because of the competition among pharmaceutical companies, they provide us with plenty of free samples (except for eptinezumab). TN is a relatively rare disorder so we can provide free samples to all of our TN patients who respond to these drugs. This is true for most neurologists’ private offices. This may not be true in big hospitals where sampling is not allowed.

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A publication of the American Headache Society, Headache, The Journal of Head and Face Pain, has just published Dr. Allan Purdy’s most generous review of my new book, The End of Migraines: 150 Ways to Stop Your Pain.

I am very grateful to Dr. Purdy and to my many colleagues who wrote endorsements for this book.

Self-publishing allows me to set a low price of $3.95 for the ebook version. It also makes it easy for me to regularly update it. Self-publishing, however, means that, unlike my previous three books, this one does not have the promotional help of a big publisher. If you read the book, please write a review on Amazon and spread the word to other migraine sufferers.

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The opioid epidemic has claimed many lives. Overprescribing by doctors has certainly played a role. The push to use opioids more liberally started in the late 1980s. This promotion by many pain experts even led to pain being adopted as the fifth vital sign. One impetus for this push was the mistaken belief in the low rates of addiction when opioids are used to treat pain. Another was the results of surveys of patients being discharged from hospitals. Poor pain control was the main complaint of 40% of such patients. Centers for Medicare & Medicaid Services (CMS) got into the act as well and included good pain control as one of the measures required for the recertification of hospitals. In January 2018, however, the three survey questions about pain management were replaced by three questions about communication about pain. In October of 2019, even these three items about communication about pain were completely removed from the CMS’ HCAHPS Survey. So hospitals and doctors no longer need to worry about relieving pain and the suffering that goes with it. Doctors have to worry more about losing their license or even being put into jail. I’ve testified in front of a disciplinary panel on behalf of a doctor who was at risk of losing his license. An adult patient’s mother complained to the state health department about her son getting prescriptions for opioid drugs. In this case, the doctor was exonerated but the financial and the emotional toll will certainly make him very unlikely to continue prescribing opioids drugs.

These drugs, despite their potential for causing addiction and other side effects, are life-savers for many people. When used judiciously and as part of a multidisciplinary approach, they can provide not only improved quality of life but can make a difference between disability and normal functioning.

A study just published in the journal Pain looked at the difficulties patients taking opioid drugs have in finding a primary care doctor.

This study examined if primary care clinics “are more or less willing to accept and prescribe opioids to patients depending on whether their history is more or less suggestive of aberrant opioid use”. They conducted an audit survey of primary care clinics in 9 states from May to July 2019. They had simulated patients call the clinics and give one of two scenarios for needing a new provider: their previous physician had either (1) retired or (2) stopped prescribing opioids for unspecified reasons. Of 452 clinics responding to both scenarios (904 calls), 193 (43%) said their providers would not prescribe opioids in either scenario, 146 (32%) said their providers might prescribe in both, and 113 (25%) responded differently to each scenario. Clinics responding differently had greater odds of willingness to prescribe when the previous doctor retired than when the doctor had stopped prescribing.

The authors concluded that “…primary care access is limited for patients taking opioids for chronic pain.” and that “This denial of care could lead to unintended harms such as worsened pain or conversion to illicit substances.”

Hopefully, the pendulum will soon begin moving closer to the middle. Another hope is that the researchers will finally discover the holy grail of pain management – a non-addictive pain medicine with few other side effects.

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Almost 1.5 million Americans visit emergency rooms every year for the treatment of head trauma. Headache, not surprisingly, is one of the most common symptoms of head trauma. What is very surprising is that until now, there have been no controlled studies of acute therapies for posttraumatic headaches.

Dr. Benjamin Friedman and his colleagues at the Montefiore Hospital in the Bronx just published a “Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache” in the journal Neurology. Emergency rooms often use metoclopramide (Reglan) as the first-line drug for the treatment of migraines. Diphenhydramine (Benadryl) was added to reduce the chance of side effects from metoclopramide. These side effects of restlessness and involuntary movements can be very unpleasant.

The study involved 160 patients. Their pain severity was measured on a 0 to 10 verbal scale. Patients who received a placebo reported a mean improvement of 3.8, while those receiving two medications improved by 5.2 points. Side effects occurred in 43% of patients who received medications and 28% of patients who received placebo.

My recent post was devoted to a study that showed dramatic similarities between migraines and posttraumatic headaches. The outcome of Friedman’s study, therefore, is not unexpected.

The overall efficacy of metoclopramide is fairly modest. It provides only partial relief that often does not last. And some patients get no relief at all. It also causes unpleasant side effects.

It is puzzling why emergency room doctors are not using a migraine-specific drug, sumatriptan for both migraines and posttraumatic headaches. An injection of sumatriptan works well within an hour for 70% of migraine patients. It has significantly fewer side effects than metoclopramide. Vials of sumatriptan (but not autoinjectors) are relatively inexpensive.

As far as the use of sumatriptan for posttraumatic headaches, we have only a few anecdotal reports. One of the reports, however, describes seven patients who did not respond to other drugs and had very good relief of their posttraumatic headaches with sumatriptan.

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We know that physical emotional, and sexual abuse in childhood increases the risk of developing chronic pain and migraines later in life. Dutch researchers looked at several other potential predisposing factors. The results of their study were published in the May issue of the journal Pain.

This study was a part of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. It included 3,064 children who were evaluated at the ages of 11, 14, 17, and 20. The researchers assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors.

From age 11 to 20 years, the prevalence of headaches increased from 9% to 20% in girls and remained in 6% to 8% range in boys. Eighty-eight percent of the girls and 76% of boys with headaches also reported at least one of the following at age 17: sleeping problems, asthma, hay fever, musculoskeletal complaints, fatigue, low mental health, or worrying. They also found that lower educational achievement, skipping breakfast on two or more days per week, and in boys, exposure to tobacco smoke in infancy, increased the risk of developing headaches. In girls, sleeping problems and musculoskeletal complaints were associated with a higher chance of having headaches. Interestingly, residential greenness reduced the chance of developing headaches.

The risk factors are usually divided into modifiable and non-modifiable. Sex, age, and genetic factors are some of the non-modifiable ones. The factors mentioned in the study, except for sex, are all theoretically modifiable. In practice, however, they are very difficult to fix. Eating breakfast every morning is probably the easiest to achieve for most families. But even that can be difficult for the very poor. Moving to suburbs for greener surroundings, improving educational opportunities, and avoiding second-hand smoke in infancy are even harder to achieve.

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Weight loss in overweight migraine sufferers – including that produced by bariatric surgery – leads to a reduction in the frequency of migraine attacks. In a previous post and in my new book I mentioned the use of metformin, a diabetes drug that helps weight loss, in migraine patients.

A study published in the February 10 issue of The New England Journal of Medicine definitively confirmed that weekly injections of another diabetes drug, semaglutide (Ozempic) can lead to an average of 15% weight loss in obese individuals. Seventy percent of participants lost at least 10% of weight. This was a double-blind, placebo-controlled trial that included 1,961 participants. Individuals in both the placebo and the active group were counseled every four weeks to encourage maintenance of a reduced calory diet and increased physical activity. Semaglutide is very similar to dulaglutide (Trulicity).

Other drugs that are used for weight loss produce an average of 4% to 6% weight loss and tend to have more side effects. Nausea and diarrhea were the most common adverse events with semaglutide. They were typically transient and mild-to-moderate in severity and subsided with time. Only 4.5% of participants on semaglutide stopped taking the drug due to side effects.

Obesity is a risk factor not only for diabetes and increased frequency of migraines but also strokes, idiopathic intracranial hypertension (pseudotumor cerebri), obstructive sleep apnea, hypertension, and others.

This trial should lead to the FDA approval of semaglutide for weight loss in obese individuals without diabetes. Hopefully, the FDA approval will compel insurance companies to pay for it. The out-of-pocket cost of 4 pen-like syringes is $735.

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The headache of low cerebrospinal fluid (CSF) pressure can be very severe. Its main feature is that it gets worse on sitting or standing and improves upon lying down. Sometimes, this change is quick but occasionally the headache slowly gets worse as the day goes on and is mildest or absent upon awakening in the morning.

Low CSF pressure often results from the needle going in too far during an epidural steroid injection for low back pain or epidural anesthesia during delivery or surgery. This results in the spinal fluid leaking into the soft tissues of the back. The loss of fluid causes sagging of the brain which normally floats in a thin layer of CSF. Spinal fluid leaks usually seal on their own but sometimes require a “blood patch”– injecting the patient’s blood into the area of the leak. The injected blood clots and seals the leak.

If a CSF leak happens after a diagnostic spinal tap or an epidural procedure, it is better to have the blood patch sooner rather than later. I recommend doing it if the headache persists for more than a couple of days.

Rarely, a spinal fluid leak occurs spontaneously after straining or without an obvious trigger. This condition is called spontaneous intracranial hypotension (SIH). A review of scientific reports of SIH involving over 2,000 patients by a British physician Dr. Manjit Matharu and his colleagues provides a good description of this condition. Headache was present in 99% of patients. In 2% the headache did not change with the change of position and 1% had no headache but only other symptoms.

The five most common symptoms of SIH besides headaches, were nausea, neck pain or stiffness, tinnitus (ringing in the ears), dizziness, and hearing problems.

The diagnosis can be made by an MRI scan with an intravenous injection of gadolinium, which is a contrast dye. According to Dr. Matharu’s review, however, MRI was normal in 19% of patients. A spinal tap to measure the pressure can be a useful test, although it was normal in one-third of patients. This is explained by the fact that intracranial pressure often fluctuates. In some patients, a spinal tap can make headaches worse. Another test is an MRI of the spine to detect an accumulation of the leaking CSF. This test was helpful only in a little more than half of the patients. A more advanced test done when other tests are negative and a blood patch is ineffective is a digital subtraction myelogram. So even when SIH is suspected – and often it is not – it may be difficult to prove the diagnosis.

In 28% of patients, bed rest and hydration were sufficient to heal the leak. A single or repeated blood patch was effective in 64% of patients. When the site of the leak is not found, most specialists do a blind patch at the lumbar level. A larger volume of blood, 20-30 ml is more effective than smaller volumes. In a small proportion of patients, surgical repair of the leak is necessary and it is done by a neurosurgeon.

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The term postural orthostatic tachycardia means that the heart rate becomes very fast upon standing up. POTS is a disorder of the autonomic nervous system that is associated with abnormal blood flow regulation. Almost all patients with POTS suffer from migraines. POTS can present with a bewildering variety of additional symptoms besides headaches (see below). This is why the diagnosis is often missed. Unfortunately, there are very few effective treatments for POTS. Making the correct diagnosis, nevertheless, is very important. It explains the cause of symptoms that are often dismissed as psychological and in some patients, treatment can lead to a dramatic improvement.

This blog was prompted by a positive study of a drug, ivabradine, to treat POTS that was published by Dr. Pam Taub and her colleagues. Ivabradine (Corlanor) is approved by the FDA to treat heart failure, so its use for POTS is “off-label”. This means that insurance companies are not likely to cover an unapproved use of a drug that costs $500 a month. With additional trials confirming that ivabradine works and with a lot of persuasion by the doctor, insurers might cover it if other treatments fail. Currently, the drugs that are used to treat POTS include beta-blockers, midodrine, fludrocortisone, and others. Increased intake of salt and fluids, exercise, dietary changes, and correction of nutritional deficiencies such as vitamin B12 and magnesium cal also help.

Here is how the Cleveland Clinic website describes POTS:
POTS symptoms can be uncomfortable and frightening experiences. Patients with POTS usually suffer from two or more of the many symptoms listed below. Not all patients with POTS have all these symptoms.
High blood pressure/low blood pressure.
High/low heart rate; racing heart rate.
Chest pain.
Dizziness/lightheadedness especially in standing up, prolonged standing in one position, or long walks.
Fainting or near-fainting.
Exhaustion/fatigue.
Abdominal pain and bloating, nausea.
Temperature deregulation (hot or cold).
Nervous, jittery feeling.
Forgetfulness and trouble focusing (brain fog).
Blurred vision.
Headaches and body pain/aches (may feel flu-like); neck pain.
Insomnia and frequent awakenings from sleep, chest pain and racing heart rate during sleep, excessive sweating.
Shakiness/tremors especially with adrenaline surges.
Discoloration of feet and hands.
Exercise intolerance.
Excessive or lack of sweating.
Diarrhea and/or constipation.

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Cyclic vomiting is considered to be a form of migraine. It is most common in children. Surveys indicate that 2% to 3% of children may be suffering from this condition. These children often develop typical migraines as they get older. Cyclic vomiting can also occur in adults. The main and usually the only symptom is intense vomiting. Vomiting occurs several times an hour with bouts lasting anywhere from an hour to several days. It is different from abdominal migraines which manifest themselves mostly by stomach pains. Nausea and vomiting can also occur, but abdominal pain is the predominant symptom. Some children progress from cyclic vomiting to abdominal migraines and then, to typical migraine headaches. Many children and adults have a family history of migraines.

To diagnose cyclic vomiting we need to consider and rule out all other possible causes of vomiting. These include gastrointestinal disorders, genetic conditions, brain tumors, and infections. An endoscopy, abdominal ultrasound, MRI scan of the brain, and blood tests are some of the usual tests.

Physical and emotional stress can trigger an attack of cyclic vomiting. Treatment is very similar to the treatment of migraines. It begins with regular sleep, exercise, relaxation training or meditation, magnesium and COq10 supplements. If attacks are frequent, preventive medications such as tricyclic antidepressants and epilepsy drugs can be useful. For acute attacks, sumatriptan nasal spray (Imitrex NS, Tosymra) and zolmitriptan nasal spray (Zomig NS) or sumatriptan injections can be effective. Antinausea drugs such as ondansetron (Zofran), metoclopramide (Reglan) and aprepitant (Emend) can be given by injection. Prochlorperazine (Compazine) and promethazine (Phenergan) are available in rectal suppositories.

This post was prompted by a review of this topic in the last issue of the journal Headache by Dr. Kovacic and Li of the Medical College of Wisconsin. It is an open-access article – you can read the entire article for free.

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Magnesium supplementation for the prevention of migraine headaches has been gaining wider acceptance. Dozens of studies, including several of our own, have shown that migraine sufferers often have a magnesium deficiency. Studies have also shown that taking an oral supplement or getting an intravenous infusion of magnesium, relieves migraines.

The causes of magnesium deficiency include genetic factors, poor absorption, stress, alcohol, and low dietary intake of foods rich in magnesium. A study just published in the journal Headache looked at the dietary intake of magnesium, including supplements, in those with migraines compared to people without migraines.

The study included 3626 participants, 20- to 50-years old. A quarter of these people suffered from migraines. People who consumed the recommended daily amount (RDA) of magnesium had a lower risk of migraine. This risk was the highest in those who were in the bottom quarter of magnesium consumption.

This was a correlational study, meaning that it does not prove that taking magnesium prevents migraines. However, common sense and our clinical experience, combined with all the previously published studies, strongly support taking magnesium to prevent migraines.

There are many other benefits of magnesium that I’ve written about in this blog – just enter “magnesium” into the search box and you will find a few dozen posts.

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My new book, The End of Migraines: 150 Ways to Stop Your Pain, was just published by Amazon. It is also available on Google Play and Kobo.
I am very grateful to all my colleagues who took the time to read the book and to provide advance praise for it.
This is a self-published book. This allows me to update it regularly and to set a very affordable price – the e-book version is only $3.95 and the paperback is $14.95. The e-book version has the advantage of having many hyperlinks to original articles and other resources.
If you read it, please write a brief review on Amazon or Google and spread the word about it.

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Persistent post-traumatic headache (PTH), paradoxically, is more common after a mild traumatic brain injury (TBI) than after a severe one.

In a recently published study, researchers in Indiana examined possible factors that may predispose people to a persistent headache after a mild TBI. They recruited 44 adult patients with mild TBI in an emergency department of a trauma center.

Participants completed a variety of psychological questionnaires and underwent tests to measure innate pain control mechanisms. Participants were classified into persistent PTH and nonpersistent PTH groups based on the 4-month data.

The results showed that patients with mild TBI who developed persistent PTH had significantly reduced pain inhibitory capacity, higher rates of depression and pain catastrophizing following injury compared to those who did not develop persistent PTH. They also found that headache pain intensity at 1–2 weeks and pain inhibitory capacity at 1–2 weeks predicted persistent PTH at 4 months after the injury.

The authors concluded that persistent PTH is more likely in people with impaired endogenous pain modulatory function and psychological processes such as depression and catastrophizing.

Catastrophizing is defined as having irrational thoughts about pain being uncontrollable, leading to disability, loss of a job, partner, ruined life, etc. Catastrophizing can be measured by questions such as “I feel it is never going to get better”, “I can’t stand it anymore”, and others.

Catastrophizing has been shown to predict the degree of pain and disability in chronic low back pain and other painful conditions.

The good news is that cognitive-behavioral therapy, multimodal treatment, and acceptance and commitment therapy can reduce catastrophizing.

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