As background to the study the investigators said, “Emerging evidence suggests that even slightly elevated intracranial pressure (ICP) can exacerbate migraine by reducing intracranial compliance and increasing trigeminal pathway sensitization. Glucagon-like peptide-1 receptor (GLP-1R) agonists, which lower cerebrospinal fluid (CSF) production, have shown success in idiopathic intracranial hypertension (IIH) by reducing ICP and improving headache frequency. Therefore, this study investigates GLP-1R agonists as a potential promising approach to alleviating migraine.”

For this pilot study, the researchers enrolled 26 obese migraine subjects (BMI ≥30).  They treated the subjects with liraglutide 1.2 mg daily for 12weeks.

They excluded patients with papilledema to rule out idiopathic intracranial hypertension.

They tracked mean monthly headache days. The primary outcome was the change in headache days after 12weeks.

They reported that mean monthly headache days decreased from 20.04 to 8.81, a statistically significant difference (p<0.001), while Migraine Disability Assessment (MIDAS) scores dropped from 62.58 to 27.23 a statistically significant mean difference of 35.35 (p<0.001).

BMI decline from 34.01 to 33.65 was not significant (p=0.060).

“Most patients felt better within the first two weeks and reported quality of life improved significantly”, said lead researcher Simone Braca,MD, a neurology resident and clinical research fellow at the Headache Centre of the University of Naples “Federico II”, Italy. “The benefit lasted for the full three-month observation period, even though weight loss was modest and statistically non-significant.”

The authors concluded, “GLP-1R agonists appear to effectively reduce migraine burden regardless of weight loss, highlighting a possible pathophysiological role of CSF volume and pressure regulation in migraine. Further, larger studies are warranted to confirm these findings.”

Using a sample of more than 2,000 older adults with migraine from the Canadian Longitudinal Study on Aging, researchers examined changes in depression status among this population during the pandemic. More than 1 in 7 older adults with migraine experienced depression for the first time during the COVID-19 pandemic, while approximately 1 in 2 with a previous history of depression experienced a recurrence during this period.

“People living with migraine are already known to be highly vulnerable to adverse mental health outcomes, such as depression,” said senior author Esme Fuller-Thomson, a professor at the University of Toronto’s Factor-Inwentash Faculty of Social Work (FIFSW) and director of the Institute for Life Course & Aging (ILCA). “Considering the increases in stressors during the pandemic, such as disruptions to medication and healthcare access, we wanted to understand how this may have impacted the mental health of those with migraine.”

The researchers looked at risk factors for depression to better understand the subpopulations of people with migraine that had the highest risk of pandemic-related depression.

Increased family conflict during the pandemic was associated with a five-fold risk of incident depression and a three-fold risk of recurrent depression.

“Many families experienced increased discord and conflict during periods of lockdown, which were coupled by declines in access to important coping mechanisms that can mitigate family stress, such as physical activity outside and time spent socializing with friends. This likely impacted the mental health challenges observed during the pandemic,” said co-author Andie MacNeil, PhD student at FIFSW.

Other pandemic-related stressors that were associated with incident depression among older adults with migraine included experiencing difficulty accessing healthcare.

“Access to comprehensive healthcare was already recognized as a major challenge for people with migraine prior to the pandemic,” said co-author Aneisha Taunque, a research assistant at the Institute for Life Course and Aging. “We know access to healthcare worsened during the pandemic, which may have exacerbated mental health challenges among this population.”

Increased time spent caregiving and/or challenges linked to caregiving were also associated with incident depression, which, like difficulties in accessing health care, approximately doubled the risk of incident depression.

“Caregiving responsibilities can be extremely challenging for people living with debilitating pain, such as that caused by migraine — and many people reported increases in their caregiving responsibilities during the pandemic,” said co-author Ying Jiang, Senior Epidemiologist at the Public Health Agency of Canada.

Other contributors to the study include Sarah Leo, a recent MSW graduate from FIFSW, Dr. Grace Li, who was a research associate with ILCA, and Margaret de Groh, a retired Scientific Manager at the Public Health Agency of Canada.

The authors emphasized the importance of ongoing research to examine depression among people with migraine.

“It will be important to identify if the observed increases were a temporary occurrence due to pandemic-related stressors, or if these trends have persisted after the pandemic,” said Fuller-Thomson. “This knowledge can help inform targeted screening and intervention for people with migraine.”

People with chronic migraine who overused pain medication had fewer monthly migraine and headache days and fewer days using pain medication when taking the migraine prevention drug atogepant.

“There is a high prevalence of pain medication overuse among people with migraine as they try to manage what are often debilitating symptoms,” said study author Peter J. Goadsby, MD, PhD, of King’s College London and a member of the American Academy of Neurology. “However, medication overuse can lead to more headaches called rebound headaches, so more effective preventive treatments are needed. Our findings are encouraging, suggesting atogepant may help reduce the need for pain medication among people with chronic migraine.”

The study involved 755 participants who had chronic migraine, defined as having 15 or more headache days per month with eight or more qualifying as migraine.

Of this group, 66% met the criteria for medication overuse defined as taking pain medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for 15 or more days in a month, triptans or ergots for 10 or more days a month, or any combination for 10 or more days.

At the start of the study, average monthly migraine days ranged from 18 to 19, and average monthly pain medication days ranged from 15 to 16.

For 12 weeks, participants were either given 30 milligrams (mg) of atogepant twice daily, 60 mg once daily, or a placebo. Atogepant is a calcitonin gene-related peptide receptor antagonist, or CGRP inhibitor. CGRP is a protein that plays a key role in starting the migraine process.

Participants recorded their migraines and headaches in an electronic diary, noting characteristics including duration and intensity, whether they experienced aura or nausea, and if they took other medications.

Researchers found for participants with medication overuse, those taking atogepant twice daily had an average of three fewer migraine days a month and three fewer headache days when compared to those taking placebo. Those taking the drug once a day had two fewer migraine days a month and two fewer headache days compared to placebo. Both groups also had three fewer days of taking pain medications to treat their symptoms when compared to placebo. Researchers say similar reductions were found among participants without medication overuse.

In those with medication overuse, 45% of those taking the drug twice daily and 42% of those taking it once a day had a 50% or more reduction in average monthly migraine days compared to 25% taking the placebo.

The number of people meeting the criteria for medication overuse also declined by 62% among those taking the drug twice daily and by 52% among those taking it once a day.

“Based on our findings, treatment with atogepant may potentially decrease the risk of developing rebound headache by reducing the use of pain medications,” said Goadsby. “This could lead to an improved quality of life for those living with migraine.”

Goadsby noted more studies are needed to evaluate the long-term safety and effectiveness of atogepant, as well as to assess the potential risk of medication overuse relapse among people with migraine.

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

The study was funded by AbbVie, the maker of atogepant. Goadsby reported that he received personal fees from AbbVie during the study.

No fewer than 11 posters from Spanish pharmacists dealt with the use of monoclonal antibodies in the management of migraine. Anti-CGRP (calcitonin gene-related peptide) antibodies bind to the receptor (e.g. erenumab) or to the CGRP molecule itself (e.g. eptinezumab, fremanezumab, and galcanezumab). Aspects explored by the Spanish researchers included real-world safety and effectiveness, switching between products and quality of life.

Real-world safety and effectiveness

Garcia-Lastra and colleagues (Aviles, Spain; poster 5PSQ-053) conducted a retrospective study of 32 patients who had received galcanezumab for prevention of migraine. Treatment was considered effective if there was a reduction of at least 50% in the migraine days per month (MDM) or a reduction of more than five points on the Headache Impact Test (HIT-6) score. The median duration of treatment was 19 months. The authors  reported that the MDM fell from 15 to 5 and the HIT-6 score fell from 69 to 57. At the end of the study period on 15.4% of patients had discontinued the drug due to side effects or ineffectiveness.

Estrada and colleagues (Badalona, Spain; poster 4CPS-043) assessed the one-year safety and efficacy of prophylactic anti-CGRP treatment with erenumab, galcanezumab and fremanezumab. A total of 42 patients was included. The authors noted that high response rates (more than 50% reduction in monthly migraine days (MMD)) were achieved with all three agents. Only three discontinued treatments due to adverse effects.

Losa-Lopez and colleagues (Sant Joan Despi, Spain; poster 4 CPS-160) examined the outcomes of long-term (12 months or more) prophylactic treatment of 64 people with chronic and episodic migraine. The mean number of migraine days (before galcanezumab treatment) was 20.46 ± 6.55 days per month for chronic migraine and 12±1.48 for episodic migraine and the mean duration of treatment was 18.4 (1.9 – 34.9) months. It is noteworthy that 20 patients discontinued galcanezumab because of lack of response.

Diaz-Perales and colleagues (Malaga, Spain; poster 5PSQ-072) looked at the real-world safety of galcanezumab in patients with chronic migraine. They reported that 17 of 110 patients discontinued treatment and of these, 29.4% did so because of intolerance. Reactions included weight gain, constipation generalised itching and local reactions. The authors noted that discontinuation due to drug intolerance was lower than reported in the pivotal trials.

Ojeda and colleagues (Barcelona, Spain; poster 4CPS-091) examined real-life persistence with treatment in 207 people who received prophylactic fremanezumab. At three-month and six-month follow-ups, persistence was 92.6% and 80.0%, respectively. The percentages of people who achieved a 50% reduction in monthly migraine days was 56.8% at three months and 54.5% at six months. A total of 27% of people developed side effects, the most common of which were allergic reactions or pruritus.

Therapeutic breaks

Some local guidelines advise a therapeutic break after 12 months treatment with an anti-CGRP agent. Two groups focused on this aspect of anti-CGRP use.

De Castro-Avedillo and colleagues (Leon, Spain; poster 4CPS-144) described the patterns of drug usage in 74 patients treated with erenumab or galcanezumab. They reported that about half the patients had to restart treatment after a therapeutic break of about six months. Of these, about half restarted with the same drug.

Similarly, Gomez and colleagues (Santander, Spain; poster 4CPS-020) described the patterns of drug usage with erenumab and galcanezumab in 273 patients.  They concluded that their results did not demonstrate high effectiveness after 12 months. Moreover, there was no difference between the two drugs.

Switching between monoclonal antibodies

In clinical practice switching between different anti-CGRP monoclonal antibodies occurs but there are no clinical trial data to support the effectiveness of this practice.

Cantudo-Cuenca and colleagues (Granada, Spain; poster 4CPS-018) analysed results from 215 patients who had failed to respond to treatment with a monoclonal antibody for three months and had then switched to another class of monoclonal antibody. They identified 110 patients treated with galcanezumab or fremanezumab (both CGRP-ligands), 24 of whom were switched to the CGRP receptor antibody, erenumab. Of 105 patients treated with erenumab, 30 were switched to a CGRP-ligand. They noted that this appeared to be a promising approach.

Mayo and colleagues (Madrid, Spain; poster 4CPS-202) reviewed a total of 55 treatments in 18 patients who had received, for at least three months, fremanezumab (225mg/month), galcanezumab (120mg/month) and erenumab (140mg/month). The mean number of headache days at baseline was 20.6 (SD 7.8) days.  However, their results showed that only a maximum of 16% of patients could be ‘rescued’, taking a 30% decrease in in the number of headache days per month as the efficacy threshold.

Symptomatic medication overuse

Chronic migraine is associated with the risk of analgesic overuse or abuse. Tudela and colleagues (Cadiz, Spain; poster 4CPS-115) evaluated 54 people suffering from chronic migraine who received at least three months treatment with fremanezumab (225mg monthly injection). The median duration of treatment was 12 months. Forty people were converted to episodic migraineurs with the monthly number of headache days falling from 28.7 (95% CI 27.1 – 30.0) to 4.0  (95% CI 3.9 – 6.4). and episodic migraine. Importantly, the percentage of these people who were classified as ‘symptomatic medication over-users’ decreased from 97.5% to 2.5%.

Quality of life

Velez and colleagues (Leon, Spain; poster 4CPS-010) evaluated quality of life (QoL) using EQ-5D-5L questionnaire in 32 patients receiving erenumab for chronic or episodic, high frequency migraine. The results showed significant reductions in frequency and intensity of migraines for 30 responders and corresponding increases in the quality of life (fewer problems with daily activities, anxiety/depression and mobility). Two patients stopped treatment due to lack of response.

The 28^th EAHP Congress took place in Bordeaux, France 20^th-22^nd March 2024. The congress theme was: Sustainable healthcare – opportunities and strategies.

After all, past research suggesting such a link during and after menopause has gotten a lot of attention.

But a pair of new studies in the journal Menopause suggest that most of them don’t need to worry as much, especially if they don’t have both migraines and long-term hot flashes and night sweats.

Instead, they should focus on tackling the other factors that can raise their cardiovascular risk by getting more sleep, exercise and healthy foods, quitting tobacco, and minding their blood pressure, blood sugar, cholesterol and weight.

For women who have experienced both migraines and hot flashes or night sweats over many years, one of the new studies does suggest an extra level of cardiovascular risk. That makes heart disease and stroke prevention even more important in this group, says study leader Catherine Kim, M.D., M.P.H., of the University of Michigan.

And for women currently in their 20s and 30s who experience migraines, the new research suggests that they might be heading for a higher risk of long-term menopause-related symptoms when they get older.

Long-term study yields important insights

Kim and her colleagues at Michigan Medicine, U-M’s academic medical center, published the new pair of studies based on an in-depth analysis of data from a long-term study of more than 1,900 women who volunteered to have regular physical exams and blood tests, and to take yearly health surveys, when they were in their late teens to early 30s.

Those women, now in their 50s and 60s, have provided researchers with a priceless view of what factors shape health in the years leading up to menopause and beyond, through their continued participation in the CARDIA study.

“The anxiety and dread that women with migraines and menopausal symptoms feel about cardiovascular risk is real – but these findings suggest that focusing on prevention, and correcting unhealthy habits and risk factors, could help most women,” said Kim, who is an associate professor of internal medicine at U-M and a primary care physician.

“For the subgroup with both migraines and early persistent hot flashes and night sweats, and for those currently experiencing migraines in their early adulthood, these findings point to an added need to control risks, and address symptoms early,” she adds.

Just over 30% of the middle-aged women in the study reported they had persistent hot flashes and night sweats, which together are called vasomotor symptoms or VMS because they relate to changes in the diameter of blood vessels.

Of them, 23% had reported also having migraines. This was the only group for whom Kim and her colleagues found extra risk of stroke, heart attack or other cardiovascular events that couldn’t be explained by other risk factors that have long been known to be linked to cardiovascular problems.

In addition to those with persistent vasomotor symptoms starting in their 40s or before, 43% of the women in the study had minimal levels of such symptoms in their 50s, and 27% experienced an increase in VMS over time into their 50s and early 60s.

The latter two groups had no excess cardiovascular risk once their other risk factors were taken into account, whether or not they had migraines. Use of hormone-based birth control and estrogen to address medical issues did not affect this risk.

Controlling destiny

In the study of data from the same women in their earlier stages of life, the researchers found that the biggest factors in predicting which ones would go on to have persistent hot flashes and night sweats were having migraines, having depression, and smoking cigarettes, as well as being Black or having less than a high school education.

“These two studies, taken together, underscore that not all women have the same experiences as they grow older, and that many can control the risk factors that might raise their chances of heart disease and stroke later in life,” said Kim. “In other words, women can do a lot to control their destiny when it comes to both menopause symptoms and cardiovascular diseases.”

She notes that the American Heart Association calls these risk factors the “Essential 8” and offers guides for what women, men and even children and teens can do to address them.

Evolving knowledge and treatment

The long-term study that the two new findings come from was specifically designed to look at cardiovascular risks when it launched in the mid-1980s. CARDIA stands for Coronary Artery Risk Development in Young Adults.

Back in the 80s, knowledge about the biology of blood vessels, down to the cellular and molecular level, was nowhere near where it is today. Both vasomotor symptoms in menopause and migraines have to do with blood vessel contraction and dilation.

But decades of research has shown the microscopic impacts on blood vessels of years of smoking, poor sleep, poor eating habits and lack of activity, as well as a person’s genetic inheritance, life experiences and hormonal history.

Newer injectable migraine medications called calcitonin gene-related peptide (CGRP) antagonists have reached the market in recent years.

Using monoclonal antibodies, they target a key receptor on the surface of blood vessel cells to prevent migraines and cluster headaches. But they are expensive and not covered by insurance for all people with migraines.

While the new study is based on data from years before these medications became available, Kim said she recommends them to her patients with persistent migraines, as well as working with them to understand what triggers their migraines and how to use other medications including pain relievers and antiseizure medications to prevent them.

She also notes that the paper on future risk of persistent hot flashes and night sweats echoes the recent trend of using antidepressant medications to try to ease these menopause effects.

Kim also says that evidence has grown about the importance of healthy sleep habits for reducing hot flashes, as well the short-term use of estradiol-based hormone therapy patches, which have not been shown to have a link to cardiovascular risk. And, she notes that research has not shown any over-the-counter supplement or herbal remedy to be effective, and that these are far less regulated than medications.

Additional authors:

Kim and Deborah Levine, M.D., M.P.H., senior author of the paper on cardiovascular risk, are both on the faculty in the Division of General Medicine, and members of the U-M Institute for Healthcare Policy and Innovation. Levine heads the Cognitive Health Services Research Program or COG-HSR. Other authors on this paper are Pamela J. Schreiner, Ph.D., of the University of Minnesota, Zhe Yin, M.S., formerly of IHPI, Rachael Whitney, Ph.D., lead statistician at COG-HSR; Stephen Sidney, MD, MPH, of Kaiser Permanente Northern California and Imo Ebong, M.D. of the University of California, Davis.

Schreiner is the senior author of the paper on later persistent VMS risk in younger women. Other authors on that paper are U-M’s Abbi Lane, Ph.D.; Zhe Yin, M.S.; Hui Jiang, Ph.D. and Richard Auchus, M.D., Ph.D.; as well as Thanh-Huyen Vu M.D., Ph.D. of Northwestern University and Cora Lewis, M.D. of the University of Alabama at Birmingham.

The study was funded by the National Heart, Lung and Blood Institute (HL169167), which also sponsors the CARDIA study.

Migraines, vasomotor symptoms, and cardiovascular disease in the Coronary Artery Risk Development in Young Adults study, Menopause, DOI: 10.1097/GME.0000000000002311

Prospective early adulthood risk factors for vasomotor symptoms in the Coronary Artery Risk Development in Young Adults study, Menopause, DOI: 10.1097/GME.0000000000002306

“There are many treatment options available to those with migraine. However, there is a lack of head-to-head comparisons of the effectiveness of these treatment options,” said study author Chia-Chun Chiang, MD, neurology specialist at the Mayo Clinic in Rochester, Minnesota, “These results confirm that triptans should be considered earlier for treating migraine, rather than reserving their use for severe attacks,” she added.

The investigators conducted a retrospective analysis of data from 3,119,517 migraine attacks during a 6-year period among 278,006 users of an e-diary smartphone application. The app allowed subjects to record migraine frequency, triggers, symptoms and medication effectiveness.

The investigators evaluated the data for the efficacy of 25 acute medications from seven drug classes —  acetaminophen, NSAIDs, triptans, combination analgesics, ergots, anti-emetics, and opioids.

The investigators used this information to compare the efficacy of each drug to ibuprofen.

“Different doses and formulations of each medication, according to the generic names, were combined in this analysis,” they noted.

The study found that the top three classes of medications which were more effective than ibuprofen were triptans, ergots and anti-emetics. Triptans were five times more effective than ibuprofen, ergots were three times more effective and anti-emetics were two and a half times more effective.

In terms of individual drugs, eletriptan which was six times more effective than ibuprofen, zolmitriptan which was five and a half times more effective and sumatriptan which was five times more effective.

Eletriptan was helpful 78% of the time, zolmitriptan was helpful 74% of the time and sumatriptan was helpful 72% of the time.

Ibuprofen was helpful 42% of the time.

Notably, NSAID drugs other than ibuprofen were 94% more effective than ibuprofen, with ketorolac being helpful 62% of the time, indomethacin being helpful 57% of the time and diclofenac being helpful 56% of the time.

Acetaminophen was helpful 37% of the time and was 17% less effective than ibuprofen.

Combination aspirin, acetaminophen and caffeine was 69% more effective than ibuprofen.

The authors concluded. “Our findings that triptans, ergots and anti-emetics are the most effective classes of medications align with the guideline recommendations and offer generalizable insights to complement clinical practice. This study provides Class IV evidence that for patients with migraine, selected acute medications (e.g., triptans, ergots, anti-emetics) are associated with higher odds of user-rated positive response than ibuprofen.”

Chaing added, “For people whose acute migraine medication is not working for them, our hope is that this study shows that there are many alternatives that work for migraine, and we encourage people to talk with their doctors about how to treat this painful and debilitating condition.”

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.

Facts:

The study was done in collaboration with Aud Nome Dueland (Headache Norway, Sandvika Neurocenter), Frank Sørgaard (former medical advisor at Novartis) and Solveig Borkenhagen with several from Oslo Economics. The results are published in the prestigious journal European Journal of Neurology.

The findings of the ELEVATE study were presented on April 25, 2023 at the annual meeting of the American Academy of Neurology.

“These results are exciting, as migraine can be debilitating, and this treatment led to fewer days with migraine for people who had already tried up to four other types of drugs to prevent migraine and either had no improvement or had side effects that outweighed any benefits,” said author Patricia Pozo-Rosich, MD, PhD, Director of Headache and Craniofacial Pain Clinical Unit at Vall d’Hebron University Hospital in Barcelona, Spain.

ELEVATE was a randomized, double-blind, placebo-controlled trial assessing the safety, tolerability, and efficacy of atogepant 60 mg once daily (QD) compared with placebo for the prevention of episodic migraine in adults who previously not responded to two to four classes of oral prophylactic treatments.

The primary endpoint was the change over a period of 12 weeks in mean monthly migraine days (MMDs).

The investigators enrolled 309 subjects. Of these, 56% had already failed to respond to two classes of oral migraine preventive medications, and 44% had already failed to respond to three or more classes.

The researchers reported that subjects in the atogepant 60 mg once daily arm group achieved a mean decrease of 4.20 days in MMDs across the 12-week treatment period, which was statistically significantly greater than the 1.85 day mean reduction achieved by the placebo group (p<0.0001).

Atogepant 60 mg once daily was well tolerated, and safety was consistent with prior studies of the drug.

The authors concluded, “Atogepant demonstrated statistically significant reductions in mean monthly migraine days among participants with CM [chronic migraine] and was safe and generally well-tolerated.

Pozo-Rosich added, “People who thought they may not find a way to prevent and treat their migraines may have hope of finding relief with a tolerable oral easy-to-use drug. This treatment was safe, well-tolerated and effective for people with difficult-to-treat migraine.”

https://www.cmaj.ca/lookup/doi/10.1503/cmaj.211969.

“The goal of treatment of migraine attacks is to provide rapid relief from pain and other migraine-related symptoms, to restore patient function and to prevent recurrence,” writes Dr. Tommy Chan, Department of Clinical Neurological Sciences, Western University, London, Ontario, with coauthors.

“A stratified approach to treatment that empowers patients to choose from different options, depending on attack symptoms and severity, and encourages them to combine medications from different classes (e.g., nonsteroidal anti-inflammatory drugs and triptans) for severe or prolonged attacks, is preferred.”

Part 2 of the review, which will be published February 6, focuses on preventive treatment to reduce the frequency and severity of migraine attacks.

As background to the new meta-analysis, investigator and author Jan Hoffmann, MD, Ph.D, of King’s College London (UK) said, “We wanted to analyze recent research to get a clearer picture of how migraines affect people’s sleep patterns and the severity of their headaches. That way, clinicians can better support people with migraines and deliver more effective sleep treatments.”

The meta-analysis of data from relevant studies was designed to evaluate sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and to evaluate basic organization of normal sleep (sleep architecture) measured using polysomnography,

The investigators searched five major medical research databases to identify studies which utilized polysomnography and/or PSQI in patients with migraine.

They excluded data from pregnant subjects and those with other headache disorders.

They identified 32 eligible studies for the meta-analysis, involving a total of 10,243 eligible subjects. Each subject had completed a questionnaire rating sleep quality, including how long it took to fall asleep, total sleep time and the use of sleep aids.

The researchers reported that adults with migraine had significantly higher (worse) PSQI scores than healthy controls (p < .001). This effect was larger in those with chronic rather than episodic migraine (p < .001).

For the studies using polysomnography, adults and children with migraine displayed a lower percentage of REM sleep. Children with migraine had less total sleep time than controls, significantly more awake time (p < .001) and significantly shorter time for sleep onset than children without migraines (p < .001). Hoffmann noted that children with migraines might fall asleep more quickly than their peers because of sleep deprivation.

The authors concluded, “People with migraine have significantly poorer subjective sleep quality and altered sleep architecture compared to healthy individuals. Further longitudinal empirical studies are required to enhance our understanding of this relationship.”

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.

This study was supported by the NIH NIA and NIAAA intramural research programs; and NIH grants including 1R01AT007813-01A1, T32 AT003378, DK056350, and UL1TR002489.

Journal Reference:

1. Ramsden, CE, et al. Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial. BMJ, July 1, 2021; DOI: 1136/bmj.n1448

The study involved 114 people between the ages of 18 and 50 who had episodic migraine. Participants experienced four to 14 headaches per month and were randomly assigned to two groups: medication-only or yoga plus medication.

The people in the yoga group were taught a one-hour yoga practice that included breathing and relaxation exercises and postures. People were supervised by a yoga instructor three days a week for one month. Then they practiced on their own at home for five days a week over the next two months. Both groups received the appropriate medications and counseling about lifestyle changes that may help with migraine, such as getting adequate sleep, eating regular meals and exercising.

Participants kept a log about how long their headaches lasted, how severe they were and medications they took.

The study showed people improved in both the medication-only group as well as the yoga group, but the benefit was higher in the yoga group in all areas, including headache frequency, pain intensity, use of medications as well as how much migraine interfered with daily life.

For headache frequency, the yoga group started with an average of 9.1 headaches per month, and ended the study reporting just 4.7 headaches per month, a 48% reduction. The medication-only group reported an average of 7.7 headaches per month at the start of the study and 6.8 at the end of the three months, a 12% decrease.

The average number of pills participants in the yoga group used decreased by 47% after three months. Meanwhile, the average number of pills the medication-only group used decreased by about 12%.

“Our results show that yoga can reduce not just the pain, but also the treatment cost of migraines,” said Bhatia. “That can be a real game changer, especially for people who struggle to afford their medication. Medications are usually prescribed first, and some can be expensive.”

One limitation of the study was that people reported information about their headaches themselves, so the results may not be consistent.

Bhatia noted that the study lasted only three months and that more research is needed to determine whether the benefits of yoga would last for a longer period.

Journal Reference:

1. Anand Kumar, Rohit Bhatia, Gautam Sharma, Dhanlika Dhanlika, Sreenivas Vishnubhatla, Rajesh Kumar Singh, Deepa Dash, Manjari Tripathi, M.V. Padma Srivastava. Effect of yoga as add-on therapy in migraine (CONTAIN). Neurology, 2020; 10.1212/WNL.0000000000009473 DOI: 1212/WNL.0000000000009473