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Headache medications

A recent national survey called the “Harris Poll Migraine Report Card” provides insight into the profound impact migraine has on people’s lives, especially those dealing with frequent attacks and high acute medication use. The survey compared those currently experiencing high-frequency migraine (8 or more attack days per month) and using acute medication on 10 or more days per month, to those who previously had this pattern but now have reduced attack frequency and medication use.

Most respondents were first diagnosed with migraine or headache disorders in their mid-20s. However, despite meeting criteria for migraine, one-third did not self-identify as having migraine disease. This underscores how migraine is still underrecognized and misdiagnosed, with people often being mislabeled with terms like “stress headache.”

Regardless of diagnosis, the burden was clear – over 50% reported a negative impact on their overall quality of life. What’s more, at least half had experienced anxiety or depression, with almost half to over half saying migraine negatively affected their mental/emotional health. These findings align with prior research showing a significant burden can start at just 4 monthly migraine days.

In an attempt to improve their condition, most made lifestyle changes like stress management, limiting caffeine and improving diet. However, their treatment choices differed – those with more frequent migraine were more likely to use newer acute treatments like gepants, diclofenac and dihydroergotamine compared to the other group using more NSAIDs, triptans and ergotamines. The high-frequency group was also more inclined to try non-pharmacological options like supplements, marijuana, massage and physical therapy.

The use of prophylactic medications was low in both groups – about 15%. There are several potential reasons including lack of access to neurologists or even primary care doctors, lack of efficacy and side effects of existing drugs, and clinicians not encouraging the use of preventive medications.

The difference between these two groups could at least in part relate to the older age of the previous high-frequency group (mean age, 47 years vs 41), as age-related improvement can occur over time.

Interestingly, the high-frequency group had poorer optimization of their current acute treatments compared to those who previously experienced high frequency but reduced their attack frequency.

This brings the controversial issue of acute medication overuse into focus – does the suboptimal acute treatment lead to frequent use of medications, rather than the current widely accepted dogma that postulates that frequent use leads to more frequent headaches?

There is evidence that caffeine and opioid analgesics make headaches worse. The evidence for triptans and NSAIDs is based purely on correlational studies. Yes, I occasionally see patients improve when they stop or reduce their intake of NSAIDs or triptans. More often improvement comes from instituting effective preventive therapies along with lifestyle changes. NSAIDs have been proven to be effective for the prevention of migraine attacks and I have dozens of patients whose migraines are well-controlled with daily prophylactic or acute use of triptans. The safety of triptans is greater than that of NSAIDs and most prophylactic medications such as antidepressants and epilepsy drugs.

The concept of acute medication “overuse” may be unhelpful and stigmatizing, as it suggests frequent attacks are the patient’s fault rather than a disease manifestation. Optimizing acute treatments may naturally reduce the need for frequent medication use as attacks improve.

 

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A study published in the current issue of JAMA Neurology examined the risk of stroke and myocardial infarction (heart attack) after starting a triptan. Triptans have been in use for over 30 years and include drugs such as sumatriptan (Imitrex), rizatriptan (Maxalt), and five others. In many countries, they are sold without a prescription. Danish researchers identified 429,612 individuals who redeemed their first prescription for a triptan.

Unlike all previous studies, they found a slight increase in the risk of stroke or heart attack. Surprisingly, in the abstract of this report, the authors present higher unadjusted numbers than in the discussion section. Of those 429,612 patients, 13 had a heart attack or a stroke within a week or two after they filled the prescription. This means that the risk is 1 in 30,000. Notably, patients who suffered from a stroke or heart attack were older than 60 and had risk factors for cardiovascular disease, such as hypertension, diabetes or previous heart attacks and strokes.

The authors concluded that their study supports the current US FDA recommendation that triptans should not be prescribed to patients with a history of coronary artery disease, transient ischemic attacks, or stroke. They also stated that their “findings do not raise concern” about triptan use in patients with low cardiovascular risk.

In a previous post, I mentioned a report that found NSAIDs such as ibuprofen, and naproxen to be more likely to cause major cardiovascular events than triptans in a ratio of 3.8 to 1. Fortunately, in high-risk patients, we can skip triptans and NSAIDs and use a new class of drugs to treat an acute migraine attack. CGRP antagonists do not increase the risk of cardiovascular events. These drugs are rimegepant (Nurtec), ubrogepant (Ubrelvy), and zavegepant (Zavzpret).

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A new report suggests that CGRP-blocking drugs (CGRP-A) are safe in pregnancy.

In the latest study, Swiss doctors examined the World Health Organization’s pharmacovigilance database and looked at reporting differences between CGRP drugs and triptans.

Triptans (drugs like sumatriptan or Imitrex and six others) were introduced over 30 years ago.  We know from pregnancy registries, retrospective, and prospective observational studies that triptans are safe in pregnancy.

The WHO database had 467 safety reports of exposure to CGRP-A in pregnancy. Of these, 386 were reports of exposure to CGRP monoclonal antibodies (mAbs), 76 to gepants, and 5 to both. The authors found “…no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy”.

CGRP drugs represent a major breakthrough in treating migraine headaches. A large proportion of migraine sufferers are women of childbearing age. We always have to consider the effect of a drug on the developing fetus. Erenumab (Aimovig), the first drug in this category was introduced almost six years ago. This is a relatively short period to assess the safety of a drug in pregnant women and the current report is not a definitive proof of safety.

There might be a difference in safety between oral CGRP antagonists (gepants), which are small molecules and injectable mAbs, which are large molecules. Gepants have the advantage of being completely washed out of the body within a few days of stopping them.  Monoclonal antibodies are injected every one or three months and can take a few months to completely leave the body. However, mAbs, being larger, cannot cross the placenta in the first trimester. So if a mAb is stopped at the beginning of pregnancy the exposure to the fetus will be small.

The gepants include ubrogepant (Ubrelvy), rimegepant (Nurtec), atogepant (Qulipta), and a nasal spray, zavegepant (Zavzpret). The monoclonal antibodies are erenumab, fremanezumab (Ajovy), galcanezumab (Emgality), and eptinezumab (Vyepti).

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A new study by Harvard researchers suggests that there is no connection between caffeine consumption and migraine headaches. I am not convinced. This study was small and had only 12 out of 97 participants consume 3-4 cups a day, while 65 consumed 1-2 cups and 20 consumed no caffeine. Statistics based on such small numbers are unreliable.

Most headache sufferers who drink large amounts of caffeine develop a caffeine-withdrawal headache when they don’t get their usual dose of caffeine on time.  My most dramatic case was that of a man who drank about 10 cups of coffee a day. He also set an alarm for 3 AM to have a cup of coffee. If he skipped that 3 AM cup, he would wake up with a debilitating migraine.

A double-blind caffeine withdrawal study published in the New England Journal of Medicine. It showed that 52% of people consuming an average of 2.5 cups of coffee developed a moderate or severe headache when caffeine was stopped.

Caffeine can play positive role in the treatment of migraine and tension-type headaches. It is considered to be an adjuvant analgesic and is included in over-the-counter and prescription drugs along with pain medications. It enhances pain relief produced by acetaminophen, aspirin, and other pain drugs.

The problem arises from excessive intake of caffeine. Two cups of coffee at breakfast, a cup of caffeinated soda at lunch, and a couple of Excedrin do not appear excessive until you consider the total amount of caffeine in these products. If you are prone to headaches, this amount may be sufficient to cause a headache, typically upon awakening in the morning.

 

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I am once again honored to participate in the annual meeting of the Headache Cooperative of the Northeast to be held March 7-9 at the Stamford Marriott Hotel and Spa in Stamford, CT.

You will get a chance to learn about the latest scientific breakthroughs from Rami Burstein, president of the International Headache Society. You will also hear from other prominent figures in the field, renowned for their pioneering work and extensive contributions over several decades – Drs. Steven Baskin, Elizabeth Loder, Thomas Ward, Morris Levin, Richard Lipton, Steven Silberstein, Allan Purdy, Alan Rapaport, Paul Rizzoli, Sait Ashina, and others.

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The annual course, “The Shifting Migraine Paradigm 2024” will be held February 15-17, 2024 at the Plaza San Antonio Hotel & Spa. This three-day conference offers an excellent update on the treatment of migraine and other headaches.

It is always an honor to be invited to speak at this event. The topic of my presentation is Supplements and Medical Foods.

 

 

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The thyroid function test is in the initial battery of blood tests we order on all our headache patients (along with RBC magnesium, vitamins D, B12, folate, and others). Having either an overactive or underactive thyroid is known to worsen migraine headaches.
A new study published by Indian researchers confirmed that treating an underactive thyroid improves headaches. The researchers studied 87 headache patients with a mild decrease in thyroid function. Half of them were prescribed thyroid medicine and the other half received a placebo. Correcting thyroid deficiency improved headache frequency, severity, and disability (MIDAS score) at three months of follow-up in the treatment group compared to the placebo group.
The conclusion was that it is logical to check thyroid function status in patients presenting with migraine headaches.
Thyroid function can sometimes decline precipitously and cause worsening of headaches without any other symptoms. This can happen after delivering a baby and the cause is often misinterpreted. Lack of sleep, stress, hormonal changes (female hormones, not thyroid hormone), occlusion of veins inside the head, and even stroke are suspected.  All those conditions can cause headaches after the delivery. But we should not forget to check the thyroid.
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Cluster headaches arguably cause the worst imaginable pain, hence the moniker, suicide headaches.  Fortunately, there are many treatments for this condition, including two FDA-approved drugs. One is sumatriptan injections taken as needed to stop an attack. The other is a preventive monthly injection of galcanezumab (Emgality). We also use Botox injections, oxygen and a variety of medications. Nevertheless, some people do not respond to these treatments.

A report by Japanese neurologists from Tokyo suggests a new treatment. One theory of the origin of cluster headaches is the reactivation of the varicella-zoster virus that causes chickenpox and shingles.

The study included over 160 patients with episodic cluster headaches who received a shingles vaccine. The response to the vaccine was measured by the amount of antibodies in the blood. Those patients who had more antibodies had a longer delay to the next cluster episode than those with low antibody counts. They also found that those who had a COVID infection and received multiple COVID vaccines, tended to do worse.

It is premature to recommend shingles vaccine to patients with cluster headaches unless they are over 50, the age when everyone is advised to get it.

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Since the legalization of medical marijuana in New York in 2014, I have prescribed it to several hundred patients. My experience suggests that approximately one-third of my patients benefit from its use and continue to rely on it for their medical needs. Some have reported relief from symptoms such as nausea and anxiety, often associated with migraines, while others find it highly effective in aiding sleep. Additionally, there are patients who have reported significant pain relief.

It is possible that the relatively low response rate I see in my patients is due to the fact that I reserve medical marijuana for those patients who do not respond to multiple drugs.

At the recent meeting of the International Headache Society, Dr. Nathaniel Schuster and his colleagues presented a study titled “Vaporized cannabis versus placebo for the acute treatment of migraine: a randomized, double-blind, placebo-controlled, crossover trial.” This study aimed to investigate the potential of medical marijuana in alleviating pain and associated migraine symptoms.

In this study, participants were instructed to treat moderate-to-severe migraine attacks within four hours of onset using vaporized cannabis flower. They were asked to treat up to four separate migraine attacks, using vaporized cannabis with different compositions: 1) THC-dominant (6% THC), 2) CBD-dominant (11% CBD), 3) THC/CBD mix (6% THC/11% CBD), and 4) placebo cannabis, with the order randomized and double-blinded.

Out of the 92 participants enrolled, 71 treated at least one migraine attack. Two hours after vaporization, the THC/CBD mix outperformed the placebo in achieving pain relief (69% vs. 48%), pain freedom (36% vs. 16%), and freedom from the most bothersome symptoms, such as nausea, photophobia, or phonophobia (62% vs. 36%). The THC-dominant option was superior to the placebo for pain relief at 2 hours (71% vs. 48%) but was not significantly different from the placebo regarding pain freedom or freedom from the most bothersome symptoms. The CBD-dominant option did not significantly differ from the placebo in terms of pain relief, pain freedom, or freedom from the most bothersome symptoms. The most common side effects reported were sleepiness, followed by euphoria, with no serious adverse events observed.

In conclusion, the authors of the study found that the acute treatment of migraine with a vaporized THC/CBD mix (6% THC/11% CBD) was superior to the placebo in terms of pain relief, pain freedom, and freedom from the most bothersome symptoms at the 2-hour mark.

This study has significant practical implications. In the past, I would leave the choice of products to the licensed pharmacist at the dispensary, while advising patients that finding the right combination is often a trial-and-error process. However, now, I will be better equipped to advise my patients on the most suitable type of medical marijuana for their specific needs based on the findings of this study.

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A presentation by Jing Jie Yu, Joshua E. Levine, and others from U. of Florida at the last meeting of the International Headache Society described their analysis of the potential risks of triptans.

Triptans are drugs that were first approved in 1992 and include sumatriptan (Imitrex, Imigran), naratriptan (Amerge, Naramig), rizatriptan (Maxalt), zolmitriptan (Zomig), eletriptan (Relpax), almotriptan (Axert),  and frovatriptan (Frova). Because triptans have the potential to constrict blood vessels they are contraindicated in patients who have coronary artery disease (CAD) or cerebrovascular disease (CVD).

The study was entitled, Association between Triptan Use and Cardiovascular Disease and All-Cause Mortality among Patients with Migraine: A Systematic Review and Meta-analysis

This meta-analysis of several studies showed that triptan use was not associated with increased risk of stroke, TIA, or all-cause death risk but with a decreased CAD risk in migraine patients.

A report presented in 2022 showed not only that triptans are safe in people without CVD, but are relatively safe even in those who have CVD. The risk of major adverse cardiovascular events with triptans was 1% while with NSAIDs, such as ibuprofen and naproxen, it was 3.8%.

 

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Magnificent Magnesium is the title of a book my colleague and friend, cardiologist Dr. Dennis Goodman wrote about this underappreciated mineral. Magnesium produces magical results, albeit only in those who are deficient.  And millions of Americans are deficient. Our research has shown that close to half of migraine sufferers are. Magnesium saves lives in cardiac care units by reducing the risk of arrhythmias. It is given intravenously for acute asthma attacks and treats eclampsia and pre-eclampsia in pregnancy. The list goes on.

A report by Canadian neurologists just published in a leading neurology journal, Neurology, describes magnesium’s role in the treatment of movement disorders. Sixty patients with low magnesium levels who had a movement disorder were identified in medical journals. Movement disorders observed were postural tremor (14 patients), resting tremor (5), intention tremor (6), ataxia involving the trunk (29) or limbs (15) and dysarthria (13), athetosis (5), myoclonus (4), and chorea (1). Some patients also had downbeat nystagmus, tetany (muscle cramping), drowsiness, vertigo, and proximal muscle weakness.

The most common culprit in these patients was a class of drugs called proton pump inhibitors (PPIs). These are drugs like omeprazole (Prilosec), pantoprazole (Protonix), esomeprazole (Nexium), and dexlansoprazole (Dexilant). They are known to interfere with the absorption of not only magnesium but also other vitamins. Long-term users of these drugs are at a higher risk of dementia, most likely because they prevent absorption of vitamin B12.  I try to get all of my patients off PPIs. This is not easy because stopping the drug causes a rebound in acid production. Some people have worse heartburn than when they started the PPI. One strategy is to replace these drugs with famotidine (Pepcid) and Rolaids (better than Tums since Rolaids have calcium and magnesium while Tums have only calcium).  After a period of time, patients are able to stop famotidine and take only Rolaids and then, stop Rolaids as well. A healthy low-acid diet, stress management, weight loss, and sleeping on the left side can also help.

#magnesium #migraine #ataxia #dysarthria #tremor #PPIs

 

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New daily persistent headache (NDPH) is condition that is defined solely by the fact that the headache begins suddenly one day and does not go away. There are no scientific studies to suggest possible underlying mechanisms or treatments. Some patients develop it after a viral infection while others, after a period of stress and many with no apparent trigger.

In my latest book, I mentioned how a seemingly benign idea of classifying medical conditions can cause harm. In case of NDPH, many anecdotal reports in medical journals indicate that this condition is not responsive to treatment. However, there are no controlled double-blind studies, only anecdotal reports. Many patients with this condition will look up this literature and conclude that there is no hope of getting better. I have seen many such devastated people. But this bleak picture is clearly wrong.

I have seen many patients with NDPH who responded to various treatments. In my 30 years of using Botox, I have found it to be one of the safest and most effective treatments for NDPH as well as migraine and other types of headaches.

At the recent meeting of the International Headache Society held in Seoul, two presentations described good responses of NDPH to Botox injections.

The first report was by S. Cheema and colleagues of Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK. They compared patients with NDPH (58) and those with chronic migraine (CM) with daily attacks (153) and chronic migraines without daily attacks (85). There was a 30% reduction in mean moderate and severe headache days in 33% of patients with NDPH, 43% with daily CM and 55% with non-daily CM.

The second report was by Shuu-Jiun Wang and colleagues of the Neurological Institute, Taipei Veterans General Hospital. They looked at the response of patients with NDPH who had predominately migraine features and those who had predominantly features of tension-type headaches. Of 228 patients diagnosed with NDPH, 199 patients (87%) had migrainous features and 29 patients (13%) had tension-type features. Their conclusion: “Through a mean follow-up duration of 2.5 years, around 40% patients with NDPH showed a favorable outcome at our headache center. Our results suggest NDPH might not be as grave as previously reported.”

Yes, these were also anecdotal reports rather than controlled trials, but they clearly show what I have also observed in my practice – NDPH is a very treatable condition. Hopefully, the next, fourth edition of the International Classification of Headache Disorders will no longer list NDPH as a diagnosis since it has no scientific basis.

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