Drug may stop migraines before headache starts

When taken at the first signs of a migraine, before headache pain begins, a drug called ubrogepant may be effective in helping people with migraine go about their daily lives with little or no symptoms, according to a new study published in the August 28, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study focused on people with migraine who could tell when an attack was about to happen, due to early symptoms such as sensitivity to light and sound, fatigue, neck pain or stiffness, or dizziness.

Ubrogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in the migraine process.

"Migraine is one of the most prevalent diseases worldwide, yet so many people who suffer from this condition do not receive treatment or report that they are not satisfied with their treatment," said study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in Bronx, New York, and Fellow of the American Academy of Neurology. "Improving care at the first signs of migraine, even before headache pain begins, can be a key to improved outcomes. Our findings are encouraging, suggesting that ubrogepant may help people with migraine function normally and go about their day."

The study involved 518 participants who had migraine for at least one year and two to eight migraine attacks per month in the three months before the study. All of the participants regularly experienced signs that a migraine would be starting within the next few hours. Participants were asked to treat two attacks during a two-month period.

Researchers divided participants into two groups. The first group received a placebo for their first set of pre-headache symptoms of migraine, followed by taking 100 milligrams (mg) of ubrogepant for their second instance of symptoms. The second group took ubrogepant for the first instance and placebo for the second instance.

Participants evaluated limitations on their activity in their diary using a scale ranging from zero to five, with 0 meaning "not at all limited -- I could do everything"; 1, "a little limited"; 2, "somewhat limited"; 3, "very limited"; or 4, "extremely limited."

Twenty-four hours after taking the drug or a placebo, 65% of people who took ubrogepant reported themselves as "not at all limited -- I could do everything," or "a little limited," compared to 48% of those who took the placebo.

Researchers found that as early as two hours post-medication, people who took the drug were 73% more likely to report that they had "no disability, able to function normally," than those who took the placebo.

"Based on our findings, treatment with ubrogepant may allow people with migraine who experience early warning signs before a migraine occurs to quickly treat migraine attacks in their earliest stages and go about their daily lives with little discomfort and disruption," said Lipton. "This could lead to an improved quality of life for those living with migraine."

Lipton noted that participants showed that based on their headache warning symptoms, they could reliably predict impending migraine headaches. These findings apply only to those with reliable warning symptoms.

A limitation of the study was that participants recorded their symptoms and medication use in electronic diaries, so it is possible some people may not have recorded all information accurately.

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Do astronauts experience 'space headaches'?

Space travel and zero gravity can take a toll on the body. A new study has found that astronauts with no prior history of headaches may experience migraine and tension-type headaches during long-haul space flight, which includes more than 10 days in space. The study was published in the March 13, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Changes in gravity caused by space flight affect the function of many parts of the body, including the brain," said study author W. P. J. van Oosterhout, MD, PhD, of Leiden University Medical Center in the Netherlands.

"The vestibular system, which affects balance and posture, has to adapt to the conflict between the signals it is expecting to receive and the actual signals it receives in the absence of normal gravity. This can lead to space motion sickness in the first week, of which headache is the most frequently reported symptom. Our study shows that headaches also occur later in space flight and could be related to an increase in pressure within the skull."

The study involved 24 astronauts from the European Space Agency, the U.S. National Aeronautics and Space Administration (NASA) and the Japan Aerospace Exploration Agency.

They were assigned to International Space Station expeditions for up to 26 weeks from November 2011 to June 2018.

Prior to the study, nine astronauts reported never having any headaches and three had a headache that interfered with daily activities in the last year.

None of them had a history of recurrent headaches or had ever been diagnosed with migraine.

Of the total participants, 22 astronauts experienced one or more episode of headache during a total of 3,596 days in space for all participants.

Astronauts completed health screenings and a questionnaire about their headache history before the flight.

During space flight, astronauts filled out a daily questionnaire for the first seven days and a weekly questionnaire each following week throughout their stay in the space station.

The astronauts reported 378 headaches in flight.

Researchers found that 92% of astronauts experienced headaches during flight compared to just 38% of them experiencing headaches prior to flight.

Of the total headaches, 170, or 90%, were tension-type headache and 19, or 10%, were migraine.

Researchers also found that headaches were of a higher intensity and more likely to be migraine-like during the first week of space flight.

During this time, 21 astronauts had one or more headaches for a total of 51 headaches.

Of the 51 headaches, 39 were considered tension-type headaches and 12 were migraine-like or probable migraine.

In the three months after return to Earth, none of the astronauts reported any headaches.

"Further research is needed to unravel the underlying causes of space headache and explore how such discoveries may provide insights into headaches occurring on Earth," said Van Oosterhout.

"Also, more effective therapies need to be developed to combat space headaches as for many astronauts this a major problem during space flights."

This research does not prove that going into space causes headaches; it only shows an association.

A limitation of the study was that astronauts reported their own symptoms, so they may not have remembered all the information accurately.

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Cheap medicines prevented migraine as well as expensive ones

Migraine is more than just a headache. Often the pain is accompanied by nausea, vomiting, light sensitivity, and sound sensitivity. Chronic migraine can be disabling and may prevent many, especially women, from contributing to working life.

Still, it often takes a long time for migraine patients to find a treatment that works well for them. Researchers at the Norwegian Center for Headache Research (NorHead) have used data from the Norwegian Prescription Register to look at which medicines best prevent migraine in people in Norway:

"There has now been done a lot of research on this subject before. This may weaken the quality of the treatment and increase the cost of treatment for this patient group," says the leader of the study, Professor Marte-Helen Bjørk at the Department of Clinical Medicine, University of Bergen.

Three medicines had better effect than the first choice of medicines

The researchers used national register data from 2010 to 2020 to estimate treatment effect. They measured this by looking at the consumption of acute migraine medicines before and after starting preventive treatment, and investigated how long the people with migraine used the different preventive treatments. A total of over one hundred thousand migraine patients were in the study.

"When the withdrawal of acute migraine medicines changed little after starting preventive medicines, or people stopped quickly on the preventive medicines, the preventive medicine was interpreted as having little effect. If the preventive medicine was used on long, uninterrupted periods, and we saw a decrease in the consumption of acute medicines, we interpreted the preventive medicine as having good effect," Bjørk explains.

As a rule, so-called beta blockers are used as the first choice to prevent migraine attacks, but the researchers found that especially three medicines had better preventive effect than these: CGRP inhibitors, amitriptyline and simvastatin.

"The latter two medicines are also established medicines used for depression, chronic pain and high cholesterol, respectively, while CGRP inhibitors are developed and used specifically for chronic migraine," says the professor.

Can have great significance for the cost of health care

CGRP inhibitors are more expensive than the other medicines. In 2021 their reimbursement amounted to 500 million NOK (not including discounts given by pharma companies).

"Our analysis shows that some established and cheaper medicines can have a similar treatment effect as the more expensive ones. This may be of great significance both for the patient group and Norwegian health care" says Bjørk.

The researchers at NorHead have already started work on a large clinical study to measure the effect of established cholesterol-lowering medicines as a preventive measure against chronic and episodic migraine.

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Consuming a diet with more fish fats, less vegetable oils can reduce migraine headaches, study finds

A diet higher in fatty fish helped frequent migraine sufferers reduce their monthly number of headaches and intensity of pain compared to participants on a diet higher in vegetable-based fats and oils, according to a new study. The findings by a team of researchers from the National Institute on Aging (NIA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the National Institutes of Health; and the University of North Carolina (UNC) at Chapel Hill, were published in the July 3 issue of The BMJ.

This study of 182 adults with frequent migraines expanded on the team's previous work on the impact of linoleic acid and chronic pain. Linoleic acid is a polyunsaturated fatty acid commonly derived in the American diet from corn, soybean, and other similar oils, as well as some nuts and seeds. The team's previous smaller studies explored if linoleic acid inflamed migraine-related pain processing tissues and pathways in the trigeminal nerve, the largest and most complex of the body's 12 cranial nerves. They found that a diet lower in linoleic acid and higher in levels of omega-3 fatty acids (like those found in fish and shellfish) could soothe this pain pathway inflammation.

In a 16-week dietary intervention, participants were randomly assigned to one of three healthy diet plans. Participants all received meal kits that included fish, vegetables, hummus, salads, and breakfast items. One group received meals that had high levels of fatty fish or oils from fatty fish and lowered linoleic acid. A second group received meals that had high levels of fatty fish and higher linoleic acid. The third group received meals with high linoleic acid and lower levels of fatty fish to mimic average U.S. intakes.

During the intervention period, participants monitored their number of migraine days, duration, and intensity, along with how their headaches affected their abilities to function at work, school, and in their social lives, and how often they needed to take pain medications. When the study began, participants averaged more than 16 headache days per month, over five hours of migraine pain per headache day, and had baseline scores showing a severe impact on quality of life despite using multiple headache medications.

The diet lower in vegetable oil and higher in fatty fish produced between 30% and 40% reductions in total headache hours per day, severe headache hours per day, and overall headache days per month compared to the control group. Blood samples from this group of participants also had lower levels of pain-related lipids. Despite the reduction in headache frequency and pain, these same participants reported only minor improvements in migraine-related overall quality of life compared to other groups in the study.

Migraine, a neurological disease, ranks among the most common causes of chronic pain, lost work time, and lowered quality of life. More than 4 million people worldwide have chronic migraine (at least 15 migraine days per month) and over 90% of sufferers are unable to work or function normally during an attack, which can last anywhere from four hours to three days. Women between the ages of 18 and 44 are especially prone to migraines, and an estimated 18% of all American women are affected. Current medications for migraine usually offer only partial relief and can have negative side effects including sedation, and the possibility of dependence or addiction.

"This research found intriguing evidence that dietary changes have potential for improving a very debilitating chronic pain condition like migraine without the related downsides of often prescribed medications," said Luigi Ferrucci, M.D., Ph.D., scientific director of NIA.

The NIH team was led by Chris Ramsden, a clinical investigator in the NIA and NIAAA intramural research programs, and UNC adjunct faculty member. Ramsden and his team specialize in the study of lipids -- fatty acid compounds found in many natural oils -- and their role in aging, especially chronic pain and neurodegenerative conditions. The UNC team was led by Doug Mann, M.D., of the Department of Neurology, and Kim Faurot, Ph.D., of the Program on Integrative Medicine. Meal plans were designed by Beth MacIntosh, M.P.H., of UNC Healthcare's Department of Nutrition and Food Services.

"Changes in diet could offer some relief for the millions of Americans who suffer from migraine pain," said Ramsden. "It's further evidence that the foods we eat can influence pain pathways."

The researchers noted that these findings serve as validation that diet-based interventions increasing omega-3 fats while reducing linoleic acid sources show better promise for helping people with migraines reduce the number and impact of headache days than fish-oil based supplements, while reducing the need for pain medications. They hope to continue to expand this work to study effects of diet on other chronic pain conditions.

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The brain of migraine sufferers is hyper-excitable

Individuals who suffer from migraine headaches appear to have a hyper-excitable visual cortex researchers at the Universities of Birmingham and Lancaster suggest.

Migraines are characterised as debilitating and persistent headaches, often accompanied by an increased sensitivity to visual or other sensory stimuli. The exact causes of these headaches are not well understood, although scientists believe they may be related to temporary changes in the chemicals, nerves, or blood vessels in the brain.

In a new study, published in the journal Neuroimage: Clinical, researchers set out to test a theory that at least part of the answer lies in the visual cortex -- the part of our brain that is responsible for vision.

Dr Terence Chun Yuen Fong, lead author on the study, explained: "Most migraineurs also report experiencing abnormal visual sensations in their everyday life, for example, elementary hallucinations, visual discomforts and extra light sensitivity. We believe this hints at a link between migraine experiences and abnormalities in the visual cortex. Our results provide the first evidence for this theory, by discovering a specific brain response pattern among migraineurs."

The study was carried out by researchers based in the Centre for Human Brain Health and School of Psychology at the University of Birmingham, and the Department of Psychology, Lancaster University. The team set up an experiment with a group of 60 volunteers, half of whom were 'migraineurs' -- regularly suffering from migraines. Participants were presented with a striped grating pattern, and asked to rate the pattern according to whether it was uncomfortable to look at, or any associated visual phenomena from viewing it.

In a further test, the participants underwent an electroencephalogram (EEG) test, in which the researchers were able to track and record brain wave patterns when the visual stimuli were presented.

In both tests, the researchers found a larger response in the visual cortex among the group of migraine sufferers when participants were presented with the gratings.

The study also took into account results from a subgroup of non-migraineurs -- participants who reported additional visual disturbances, a common feature of migraines. Surprisingly, it was found that these participants also showed hyperexcitability in the response of their visual cortex.

Dr Ali Mazaheri, the senior author on the paper, explains: "Our study provides evidence that there are likely specific anomalies present in the way the visual cortex of migraine sufferers processes information from the outside world. However, we suspect that is only part of the picture, since the same patterns of activity can also be seen in non-migraineurs who are sensitive to certain visual stimuli."

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Migraine headaches? Consider aspirin for treatment and prevention

Migraine headache is the third most common disease in the world affecting about 1 in 7 people. More prevalent than diabetes, epilepsy and asthma combined, migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers. Migraines also are associated with an increased risk of stroke.

There are effective prescription medications available to treat acute migraine headaches as well as to prevent recurrent attacks. Nonetheless, in the United States many patients are not adequately treated for reasons that include limited access to health care providers and lack of health insurance or high co-pays, which make expensive medications of proven benefit unaffordable. The rates of uninsured or underinsured individuals have been estimated to be 8.5 percent nationwide and 13 percent in Florida. Furthermore, for all patients, the prescription drugs may be poorly tolerated or contraindicated.

Researchers from Florida Atlantic University's Schmidt College of Medicine have proposed aspirin as a possible option for consideration by primary care providers who treat the majority of patients with migraine. Their review includes evidence from 13 randomized trials of the treatment of migraine in 4,222 patients and tens of thousands of patients in prevention of recurrent attacks.

Their findings, published in the American Journal of Medicine, suggest that high-dose aspirin, in doses from 900 to 1,300 milligrams given at the onset of symptoms, is an effective and safe treatment option for acute migraine headaches. In addition, some but not all randomized trials suggest the possibility that daily aspirin in doses from 81 to 325 milligrams may be an effective and safe treatment option for the prevention of recurrent migraine headaches.

"Our review supports the use of high dose aspirin to treat acute migraine as well as low dose daily aspirin to prevent recurrent attacks," said Charles H. Hennekens, M.D., Dr.PH, corresponding author, first Sir Richard Doll Professor and senior academic advisor in FAU's Schmidt College of Medicine. "Moreover, the relatively favorable side effect profile of aspirin and extremely low costs compared with other prescription drug therapies may provide additional clinical options for primary health care providers treating acute as well as recurrent migraine headaches."

Common symptoms of migraine include a headache that often begins as a dull pain and then grows into a throbbing pain, which can be incapacitating and often occurs with nausea and vomiting, and sensitivity to sound, light and smell. Migraines can last anywhere from four to 72 hours and may occur as many times as several times a week to only once a year.

"Migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers," said Bianca Biglione, first author and a second-year medical student in FAU's Schmidt College of Medicine. "In fact, about 1 in 10 primary care patients present with headache and three out of four are migraines. Aspirin is readily available without a prescription, is inexpensive, and based on our review, was shown to be effective in many migraine patients when compared with alternative more expensive therapies."

Approximately 36 million Americans suffer from migraine headaches and the cause of this disabling disorder is not well understood. There is a higher prevalence in women (18 percent) than men (9 percent). In women, the prevalence is highest during childbearing age.

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Cannabis reduces headache and migraine pain by nearly half

Inhaled cannabis reduces self-reported headache severity by 47.3% and migraine severity by 49.6%, according to a recent study led by Carrie Cuttler, a Washington State University assistant professor of psychology.

The study, published online recently in the Journal of Pain, is the first to use big data from headache and migraine patients using cannabis in real time. Previous studies have asked patients to recall the effect of cannabis use in the past. There has been one clinical trial indicating that cannabis was better than ibuprofen in alleviating headache, but it used nabilone, a synthetic cannabinoid drug.

"We were motivated to do this study because a substantial number of people say they use cannabis for headache and migraine, but surprisingly few studies had addressed the topic," said Cuttler, the lead author on the paper.

In the WSU study, researchers analyzed archival data from the Strainprint app, which allows patients to track symptoms before and after using medical cannabis purchased from Canadian producers and distributors. The information was submitted by more than 1,300 patients who used the app over 12,200 times to track changes in headache from before to after cannabis use, and another 653 who used the app more than 7,400 times to track changes in migraine severity.

"We wanted to approach this in an ecologically valid way, which is to look at actual patients using whole plant cannabis to medicate in their own homes and environments," Cuttler said. "These are also very big data, so we can more appropriately and accurately generalize to the greater population of patients using cannabis to manage these conditions."

Cuttler and her colleagues saw no evidence that cannabis caused "overuse headache," a pitfall of more conventional treatments which can make patients' headaches worse over time. However, they did see patients using larger doses of cannabis over time, indicting they may be developing tolerance to the drug.

The study found a small gender difference with significantly more sessions involving headache reduction reported by men (90.0%) than by women (89.1%). The researchers also noted that cannabis concentrates, such as cannabis oil, produced a larger reduction in headache severity ratings than cannabis flower.

There was, however, no significant difference in pain reduction among cannabis strains that were higher or lower in levels of tetrahydrocannabinol (THC) and cannabidiol (CBD), two of the most commonly studied chemical constituents in cannabis, also known as cannabinoids. Since cannabis is made up of over 100 cannabinoids, this finding suggests that different cannabinoids or other constituents like terpenes may play the central role in headache and migraine relief.

More research is needed, and Cuttler acknowledges the limitations of the Strainprint study since it relies on a self-selected group of people who may already anticipate that cannabis will work to alleviate their symptoms, and it was not possible to employ a placebo control group.

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1-2 caffeinated drinks not linked with higher risk of migraines; 3+ may trigger them

Afflicting more than one billion adults worldwide, migraine is the third most prevalent illness in the world. In addition to severe headache, symptoms of migraine can include nausea, changes in mood, sensitivity to light and sound, as well as visual and auditory hallucinations. People who suffer from migraine report that weather patterns, sleep disturbances, hormonal changes, stress, medications and certain foods or beverages can bring on migraine attacks. However, few studies have evaluated the immediate effects of these suspected triggers.

In a study published today in the American Journal of Medicine, researchers at Beth Israel Deaconess Medical Center (BIDMC), Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health (HSPH) evaluated the role of caffeinated beverages as a potential trigger of migraine. Led by Elizabeth Mostofsky, ScD, an investigator in BIDMC's Cardiovascular Epidemiology Research Unit and a member of the Department of Epidemiology at HSPH, researchers found that, among patients who experience episodic migraine, one to two servings of caffeinated beverages were not associated with headaches on that day, but three or more servings of caffeinated beverages may be associated with higher odds of migraine headache occurrence on that day or the following day.

"While some potential triggers -- such as lack of sleep -- may only increase migraine risk, the role of caffeine is particularly complex, because it may trigger an attack but also helps control symptoms," said Mostofsky. "Caffeine's impact depends both on dose and on frequency, but because there have been few prospective studies on the immediate risk of migraine headaches following caffeinated beverage intake, there is limited evidence to formulate dietary recommendations for people with migraines."

In their prospective cohort study, Mostofsky and colleagues -- including Principal Investigator Suzanne M. Bertisch, MD, MPH, of the Division of Sleep and Circadian Disorders at Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, and Harvard Medical School -- 98 adults with frequent episodic migraine completed electronic diaries every morning and every evening for at least six weeks. Every day, participants reported the total servings of caffeinated coffee, tea, soda and energy drinks they consumed, as well as filled out twice daily headache reports detailing the onset, duration, intensity, and medications used for migraines since the previous diary entry. Participants also provided detailed information about other common migraine triggers, including medication use, alcoholic beverage intake, activity levels, depressive symptoms, psychological stress, sleep patterns and menstrual cycles.

To evaluate the link between caffeinated beverage intake and migraine headache on the same day or on the following day, Mostofsky, Bertisch and colleagues used a self-matched analysis, comparing an individual participant's incidence of migraines on days with caffeinated beverage intake to that same participant's incidence of migraines on days with no caffeinated beverage intake. This self-matching eliminated the potential for factors such as sex, age, and other individual demographic, behavioral and environmental factors to confound the data. The researchers further matched headache incidence by day of the week, eliminating weekend versus week day habits that may also impact migraine occurrence.

Self-matching also allowed for the variations in caffeine dose across different types of beverages and preparations.

"One serving of caffeine is typically defined as eight ounces or one cup of caffeinated coffee, six ounces of tea, a 12-ounce can of soda and a 2-ounce can of an energy drink," said Mostofsky. "Those servings contain anywhere from 25 to 150 milligrams of caffeine, so we cannot quantify the amount of caffeine that is associated with heightened risk of migraine. However, in this self-matched analysis over only six weeks, each participant's choice and preparation of caffeinated beverages should be fairly consistent."

Overall, the researchers saw no association between one to two servings of caffeinated beverages and the odds of headaches on the same day, but they did see higher odds of same-day headaches on days with three or more servings of caffeinated beverages. However, among people who rarely consumed caffeinated beverages, even one to two servings increased the odds of having a headache that day.

"Despite the high prevalence of migraine and often debilitating symptoms, effective migraine prevention remains elusive for many patients," said Bertisch. "This study was a novel opportunity to examine the short-term effects of daily caffeinated beverage intake on the risk of migraine headaches. Interestingly, despite some patients with episodic migraine thinking they need to avoid caffeine, we found that drinking one to two servings/day was not associated with higher risk of headache. More work is needed to confirm these findings, but it is an important first step."

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