Recent research in migraine include links to omega-3s, fibromyalgia, marijuana, opioids
June is Migraine and Headache Awareness Month, according to the American Migraine Foundation. The condition impacts almost one in five women, one in 10 children and one in 20 men, according to the Migraine Research Foundation.
Although an American Journal of Medicine study indicates the first migraine may have occurred more than 3,000 years ago, there is still not a complete understanding of the condition, according to Mia T. Minen, MD, MPH, assistant professor in the department of neurology and director of headache services at NYU Langone Health.
“Primary care physicians often think a patient has a sinus headache and prescribe antibiotics, when in fact the patient has a migraine, which is distinguished by its severe intensity,” she told Healio Primary Care.
Kathleen Digre, MD, president of the American Headache Society division and chief of headache and neuro-ophthalmology at the University of Utah, said that short visits with numerous guidelines to follow contribute to PCP misdiagnoses.
“There is a problem with our health care system that keeps these clinicians from spending enough time with their patients. Consequently, PCPs sometimes misdiagnose tension headache for migraine,” she said in an interview. “It is critical that these clinicians learn a few tricks about diagnosing and treating migraine.”
In recognition of Migraine and Headache Awareness Month, Healio Primary Care summarized several recent developments in migraine research that PCPs can consider in their practices immediately.
ID-Migraine tool recommended for diagnosing migraine
The ID-Migraine tool was recommended for identifying migraine, according to a systematic review recently published in Cephalalgia.
“There is, to our knowledge, no overview of diagnostic accuracy of the different headache measurement instruments related to the level of evidence,” Hedwig A van der Meer, PhD candidate at the University of Applied Sciences, Amsterdam, the Netherlands, and colleagues wrote.
Researchers assessed 31 studies that rated 11 migraine diagnostic tools based on their diagnostic accuracy and ultimately recommended the ID-Migraine, with its pooled sensitivity of 0.87 (95% CI, 0.85–0.89) and specificity of 0.75 (95% CI, 0.72–0.78).
The National Headache Foundation also indicates ID-Migraine might be an effective tool. The organization's website states that "answering yes to two out of three of these simple questions effectively identifies migraine sufferers."
- “Has a headache limited your activities for a day or more in the last 3 months?”
- "Are you nauseated or sick to your stomach when you have a headache?"
- "Does light bother you when you have a headache?"
Van der Meer and colleagues cautioned that many of the tools analyzed for the Cephalalgia review had only one study that assessed them, increasing the risk for bias.
“Future research should use the recommended measurement instruments and validate them in different samples of the same population to increase the level of certainty that the diagnostic accuracy is realistic,” Van der Meer and colleagues wrote.
Omega-3s may prevent migraine
Patients who consumed long chain omega-3 polyunsaturated fatty acids had lower instances of headache, according to an analysis recently published in Prostaglandins, Leukotrienes & Essential Fatty Acids.
“It is unknown whether the levels of omega-3 PUFAs consumed in the population at large are associated with headache in the absence of a strict dietary intervention and counselling,” Anne E. Sanders, MS, PhD, of the Center for Pain Research and Innovation, University of North Carolina at Chapel Hill, and colleagues wrote.
They reviewed survey data and interviews from 2,463 men and women aged 20 years and older with severe headache or migraine.
Sanders and colleagues found that those men and women with higher intake of eicosapentaenoic acid and docosahexaenoic acid from cold-water fatty fish, such as salmon, mackerel, tuna, herring, and sardines; flaxseed, chia seeds, and walnuts; and fortified eggs, yogurt, juices, milk, soy beverages were associated with lower prevalence of headache. In addition, the link was not as prevalent in those who obtained their eicosapentaenoic acid and docosahexaenoic acid from supplements.
“Severe headache and migraine are common neurological disorders, costly to treat and not adequately managed by pharmaceutical therapy. Our findings provide useful population level evidence that is consistent with the hypothesis that [long chain omega-3 polyunsaturated fatty acids] are beneficial in preventing and managing chronic pain,” Sanders and colleagues wrote.
Patients with migraine may need to be screened for additional conditions
Data gleaned from more than 30,000 electronic health records prompted researchers to recommend screening patients presenting with headache for fibromyalgia and medication overuse, according to an abstract at the American Academy of Neurology annual meeting.
“The biggest concern is that chronic migraine with medication overuse, if not addressed, can contribute to worsening fibromyalgia pain and central sensitization,” Erin Bettendorf, MD, of the anesthesia and pain medicine department at the University of Washington and colleagues wrote.
They reviewed 33,389 EHRs and found patients with a diagnosis of migraine were concurrently diagnosed with fibromyalgia at a rate of 6%. In addition, 9.9% of the 2,427patients diagnosed with chronic migraine were also diagnosed with fibromyalgia and 20% of the 7,164 those diagnosed with fibromyalgia were also diagnosed with migraine. Also, , medication overuse headache was diagnosed in 1% of the patients with fibromyalgia and of those patients, 82% had migraine headaches.
“There is likely under-diagnosis of comorbid migraine, medication overuse headache and fibromyalgia and vice-versa,” Bettendorf and colleagues wrote.
“We recommend a screen for fibromyalgia and medication overuse in all patients presenting with headache, since comorbidity with other headaches is high and patients often do not spontaneously report symptoms. Medication overuse headache needs to be addressed in patients with comorbid migraine and fibromyalgia in order be more likely to succeed with any other treatments,” they added.
FDA-approved migraine prevention therapies produce additional positive results
Recent trials involving Aimovig, Ajovy and Emgality — the three migraine prevention drugs that received FDA approval in 2018 — yielded favorable results, according to abstracts presented at the American Academy of Neurology annual meeting.
Aimovig (erenumab-aooe, Amgen)’s 1-year, open label extension study comprised 609 patients with chronic migraine who participated in a 12-week, double-blind, placebo-controlled parent study, Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, and colleagues wrote.
Researchers 350 provided patients with a 70-mg dose and 259 patients with a 140-mg dose of the drug. They reported that at study’s end, there was a greater than 50% reduction in monthly migraine days in 53.3% of those patients who received the smaller dose and 67.3% of those who received the larger dose.
“One year of erenumab-aooe was safe and well tolerated, with sustained efficacy,” Tepper and colleagues concluded.
Ajovy (fremanezumab-vfrm, Teva)’s 52-week, multicenter, randomized, double-blind, parallel-group study included 1,494 adults with chronic and episodic migraine who completed placebo-controlled studies.
“Migraine attacks are characterized by disabling and painful attacks and individuals with chronic migraine have even greater burdens due to the persistence of the disorder,” Teshamae Monteith, MD, chief of headache division at the University of Miami’s Miller School of Medicine, told Healio Primary Care.
Participants either received a starting dose of 675 mg and then 225 mg monthly for 11 months or a quarterly dose of 675 mg every 3 months for 12 months. At study’s end, all patients had a mean reduction of at least 2 migraine days.
“Fremanezumab is moving many patients with chronic migraine to episodic migraine status and giving them a greater quality of life,” Monteith noted.
Emgality (galcanezumab-gnlm, Eli Lilly)’s 3-month study and a 9-month open-label extension, double-blind, placebo-controlled trial showed a significant reduction in the number of migraine days.
Patients with chronic migraine and a mean of 19.4 headache days were randomized to monthly subcutaneous injections of placebo (n = 558), 120 mg of galcanezumab with a 240 mg loading dose (n = 278) or a 240 mg dose of galcanezumab (n = 277) Holland Detke, PhD, a clinical research advisor at Eli Lilly and Company, and colleagues wrote, adding that at month 12, participants indicated 8 to 9 fewer migraine days.
“Galcanezumab showed further increases in effectiveness and patient functioning and was safe and well-tolerated, with high adherence during 1-year treatment for chronic migraine,” they wrote.
Medical cannabis may alleviate chronic migraine symptoms
Patients with chronic migraine who took medical cannabis saw decreases in some of the headache’s associated symptoms, an abstract discussed at the American Academy of Neurology annual meeting revealed.
“No guidelines exist for the use of [medical cannabis] in [chronic migraine] patients. The limited body of literature for medical cannabis leaves providers underequipped and patients vulnerable,” Laszlo Mechtler, MD, from the DENT Neurologic Institute in Amherst, New York and colleagues wrote.
Researchers retrospectively reviewed the charts of 316 patients older than 21 years who had experienced migraine and had used medical cannabis for at least 1 month. They found 121 patients reported sleep improvements, 111 noted a reduction of 50% or more of headache days, 97 reported anxiety improvement and 78 noted mood improvement.
“Medical cannabis may play a safe role in chronic migraine management. ... Prospective studies are required to examine the role of medical cannabis in chronic migraine within a placebo-controlled environment,” Mechtler and colleagues concluded.
Unsatisfied triptan users more than 10 times likely to receive opioids
Patients with migraine who found triptans ineffective often received opioids and sometimes had another headache, an abstract presented at the American Academy of Neurology annual meeting suggested.
Researchers said the findings should prompt all PCPs with patients on triptans to reconsider the treatment regimen they had prescribed.
“Real-world observational studies have demonstrated low persistence with triptans. Data related to outcomes among patients inadequately managed on triptans are limited,” Stephen D. Silberstein, MD, director of the Jefferson Headache Center at Thomas Jefferson University, and colleagues wrote.
Researchers analyzed data from 331 patients who were considered insufficient triptan responders — they had an extant triptan prescription or had received such medications in the past 6 months and did not achieve pain freedom 2 hours post dose, or responded to the therapy but stopped due to the absence of efficacy or the presence of adverse events.
Silberstein and colleagues found the insufficient responders were 13 times more likely to receive an opioid and three times more likely to experience a rebound headache than those patients who had a positive response to triptans.
“Ask yourself if the wrong triptan was used, if it was administered the wrong way or if your patient needs to move to a new class of drugs all together. Keep in mind though, that insurance companies may not be willing to entirely cover the cost of [Aimovig, Ajovy, Emgality] until generics of those medications become available,” Silberstein told Healio Primary Care.
Nearly half of acute migraine treatment users also use opioids
About 50% of patients using prescription acute treatments for migraine simultaneously use opioids or barbiturates, study data presented at the American Academy of Neurology annual meeting showed.
Aubrey Manack Adams, PhD, a global therapeutic area lead for migraine at Allergan and colleagues reviewed 13,624 surveys from patients who met the criteria for migraine.
They found 1,719 had stopped using their acute prescription migraine medication. Other findings involving this patient subset include:
- 23% of those with migraine are using a prescription acute treatment to manage their disease and of those, 47% concurrently use an opioid or barbiturate;
- 35.5% of those with migraine who ever tried an acute prescription medication stopped their treatment;
- 67.5% of lapsed users indicated they were previously diagnosed with migraine; and
- 87.5% had stopped seeing the health care professional responsible for helping them manage their headaches.
“[Some of] these data confirm the need for acute treatments for migraines. Primary care physicians need to diagnose migraine, explain acute treatment options and keep aware of new treatment options that may become available for their patients,” she continued.
Current acute treatment for migraine include triptans, ergotamine drugs, analgesics and NSAIDs, according to the National Institute of Neurological Disorders and Stroke and American Migraine Foundation websites. – by Janel Miller
Adams AM, et al. Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study demonstrate a high level of unmet need for migraine treatment in people who discontinue acute prescription migraine medication.
Bettendorf E, et al. Pain compounding pain: Fibromyalgia and migraine comorbidity.
Detke H, et al. One-year treatment with galcanezumab in patients with chronic migraine: Results from the open-label phase of the REGAIN Study.
Goadsby P, et al. Long-term efficacy and safety of fremanezumab in migraine: Results of a 1-Year study.
Mechtler L, et al. Medical cannabis for chronic migraine: A retrospective review.
Silberstein SD, et al. Opioid use, rebound headache, and resource utilization among migraine patients with insufficient response to triptans based on real-world data.
Tepper SJ, et al. Assessment of the long-term safety and efficacy of erenumab during open-label treatment of patients with chronic migraine.
All presented at:
American Academy of Neurology Annual Meeting. May 4-10, 2019, Philadelphia.
American Migraine Foundation "Commonly used acute migraine treatments." Accessed June 13, 2019. https://americanmigrainefoundation.org/resource-library/commonly-used-acute-migraine-treatments/
Migraine Research Foundation "Migraine facts." https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed June 7, 2019.
National Headache Foundation. “Headache management tools: ID Migraine.” https://headaches.org/2007/11/16/headache-management-tools-id-migraine/. Accessed June 13, 2019.
NIH National Institute of Neurological Disorders and Stroke Migraine Information Page.
NIH "Omega-3 fatty acids." https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/. June 12, 2019.
https://www.ninds.nih.gov/Disorders/All-Disorders/Migraine-Information-Page. Accessed June 12, 2019
Rizzoli P, Mullally WJ. Am J Med. https://doi.org/10.1016/j.amjmed.2017.09.005.
Sanders AE, et al. Prostaglandins Leukot Essent Fatty Acids. 2018;doi:10.1016/j.plefa.2018.06.008.
van der Meer HA, et al. Cephalalgia. 2019;doi:10.1177/0333102419840777.
Adams works for Allergan, Digre is president of the American Headache Society, Minen reports receiving a grant from NIH, Monteith reports serving as an advisor and site principal investigator for research sponsored by Teva. Healio Primary Care was unable to obtain relevant financial disclosures for the other abstract authors prior to publication. Please see the studies for those authors’ relevant financial disclosures.