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Migraine Overview and Summary of Current and Emerging Treatment Options
Golden L. Peters, PharmD, BCPS
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Migraine Overview and Summary of Current and Emerging Treatment Options

Golden L. Peters, PharmD, BCPS
Migraine is a leading cause of disability worldwide. Approximately 15% of Americans experience migraines. Most people who have migraines feel that people who do not have them often underestimate their condition. Migraines affect people’s quality of life and ability to participate in work, family, and social events. A new class of medication, calcitonin gene-related peptide (CGRP) antagonists, has been approved for migraine prevention in adults. The newly approved CGRP antagonists are erenumab, fremanezumab, and galcanezumab, while eptinezumab looks to 2020 for approval. Lasmiditan, ubrogepant, and rimegepant are currently emerging acute migraine therapies that may be added to the arsenal of current migraine management.
Am J Manag Care. 2019;25:-S0
Introduction to Migraine

The reach of migraine headaches spans the globe.1 Migraine is sometimes confused with other types of headache, such as tension headache. Those with migraines may not receive the correct diagnosis, adequate treatment, or proper support from family, friends, or coworkers. Migraine treatment usually consists of acute or abortive medications, whereas preventive medications are used by a minority of individuals with migraine. The triptans, or selective serotonin 5-HT1B/1D receptor agonists, were approved for acute migraine therapy in the 1990s.2 The calcitonin gene-related peptide (CGRP) antagonists approved in 2018 are the first class of medications specifically approved for migraine prevention, contrary to all the other migraine agents that are also used for other conditions. There are 3 newly approved CGRP monoclonal antibodies (mAbs) and a fourth mAb, a ditan, and 2 CGRP receptor antagonists (gepants) in development for migraine treatments. Erenumab, fremanezumab, and galcanezumab are newly approved CGRP mAbs for the prevention of migraines in adults. The emerging migraine treatments include the mAb eptinezumab, the ditan lasmiditan, and gepants ubrogepant and rimegepant.


Migraines are a leading cause of disability and suffering worldwide. 3 Migraine was ranked as the sixth cause of years lost due to disability globally in 2013.3 Head pain or headache accounted for 3% of emergency department (ED) visits annually and was the fourth or fifth leading reason for patients to visit the ED.1 In a review by Burch et al, various US government health surveys were analyzed to examine the prevalence and impact of migraines. According to the review, 1 in 6 individuals in the United States are affected by migraines. Contrary to most chronic conditions, people who are usually healthy and young or middle-aged are largely affected. In Americans aged 15 to 64 years, approximately 1 in 6 people and 1 in 5 women have reported either severe headaches or migraines in the past 3 months. The review also reported the highest migraine prevalence in people aged 18 to 44 years. Of this group, 17.9% experienced a migraine within the previous 3 months. The prevalence of migraines decreases as people age. For those aged 45 to 64 years, the prevalence was 15.9%, followed by 7.3% for those aged 65 to 74 years and 5.1% in individuals 75 years and older.1

When examining other factors, Burch et al discovered differences regarding gender, ethnicity, work status, income, and insurance type.1 Women were more prone than men to experience migraines. In 1 of the government surveys examined, the 2015 National Health Interview Study reported the overall prevalence of migraines or severe headache to be 15.3%, with 20.7% prevalence in women and 9.7% prevalence in men. This has remained stable when compared with data from 2006 to 2015. In contrast to previous reports, 18.4% of native Americans (Alaskan natives or American Indians) were the most affected ethnicity compared with white, black, or Hispanic individuals.4,5 People who worked full-time reported the least number of severe headaches or migraines (13.2%) compared with people working part-time (15.6%), those who were unemployed or had never worked (16.6%), and those who were unemployed but had previously worked (21.4%). Migraine prevalence was highest in those living below the poverty level (21.7%) and with an annual household income of less than $35,000 (19.9%). This may be explained by increased exposure to migraine triggers and decreased access to treatment and healthcare resources. Burch et al divided the findings relative to insurance by age in 2 groups, younger than 65 years and 65 years and older. In people younger than 65 years, those with Medicaid had the highest migraine prevalence (26.0%) as compared with those with no insurance (17.1%) and private insurance (15.1%). In those 65 years and older, participants with both Medicare and Medicaid coverage had the highest prevalence at 16.4% compared with those with Medicare Advantage (6.7%), Medicare only (5.8%), private insurance (4.4%), and other coverage (5.9%). The estimate for the uninsured patients in this age range was considered unreliable due to a relative standard error over 50% and therefore not reported.3

Headache Types

There are several headache classifications outlined by the International Headache Society Headache Classification Committee.6 The more common headaches are outlined in Table 1.6 Migraines are classified as with or without aura. Migraines with aura have fully reversible sensory, visual, or other symptoms related to the central nervous system. The aura usually begins before migraine onset but may occur with headache onset or after the headache has stopped. The most common type of aura in patients with migraine is visual aura, followed by sensory disturbances, and, less frequently, speech disturbances. Sensory disturbances may include a pins-and-needles sensation that slowly travels from a point of origin and affects 1 side of the tongue, body, and/or face. It may also be accompanied by numbness; however, numbness may also occur independently as the only symptom. Speech disturbances are usually aphasic and more difficult to categorize. The prodromal phase occurs hours to days before a headache and/or as a postdromal phase after the headache has resolved. Pro- and postdromal symptoms may include pain, fatigue, neck stiffness, hypo- or hyperactivity, food cravings, repetitive yawning, and/or depression. Prodromal symptoms may also include various combinations of pallor, blurred vision, fatigue, yawning, difficulty concentrating, nausea, and sensitivity to sound and/or light.6

Episodic migraines are defined as headaches occurring less than 15 days per month.7 Chronic migraines are defined as headache occurring on 15 or more days per month for more than 3 months with at least 8 days having migraine features.6 Transformed migraines is an additional term used to describe chronic migraines because they evolve from episodic migraines.7 Medication-overuse headaches are the most common cause of symptoms suggestive of chronic migraine.6 It is defined as taking opioids, triptans, ergotamine, or combination analgesics for more than 9 days monthly, and aspirin, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDs) for more than 14 days monthly.6 Since the use of combination butalbital products or opioids for fewer than 9 days monthly may increase migraine frequency, these medications should generally be avoided.7,8 Once the medication is withdrawn, approximately 50% of patients return to episodic migraines, suggesting the patient was misdiagnosed with chronic migraines.6

Fewer than 10% of women experience migraines associated with their menstrual cycles. Most women with migraines do not have an aura with menstrual migraines. These attacks are usually coupled with more severe nausea and last longer than nonmenstrual cycle attacks.6

Risk Factors

There are several risk factors associated with migraine occurrence. Nonmodifiable factors include genetics, gender, and age. The probability of migraines is 40% in a person with 1 parent with migraines and 75% if both parents experience migraines. Adult women are 3 times more likely than men to have migraines. However, in preadolescents, migraines are more common in boys. Migraines usually have an onset in late childhood/early adolescence, and the prevalence peaks in individuals in their 50s, with notable decreases as people enter their 60s and 70s and rare occurrences in people 80 years and older.9

Ineffective acute treatment,10 acute migraine medication overuse,5,7,11-16 obesity,17,18 and stressful life events5,19 are modifiable risk factors that may increase the risk of progression from episodic to chronic migraines.19 It is also important to note that patients who did not believe they could influence their headache or felt that their headache was due to fate or chance are more likely to insufficiently manage their headaches, resulting in poorer overall disability.20,21 These factors highlight the need for education on methods to best manage and cope with migraines. Healthcare professionals should educate patients on protective factors that may increase the migraine threshold, including the use of migraine-preventive medication,22 physical exercise, and stress management.19

Migraine triggers are patient specific. Examples include food additives, caffeine, artificial sweeteners, and delayed or missed meals. To determine the probability of an item being a trigger, patients should avoid the item for at least 4 weeks and then slowly reintroduce it, keeping in mind that migraines may start 24 to 48 hours before headache onset.9

Stigma and Impact on the Individual

In 2017, Neilsen conducted a survey sponsored by Eli Lilly, resulting in the Migraine Impact Report.23,24 The report examined the economic, physical, and social impact of migraines. Of the 1018 US adult respondents, 518 were medically diagnosed with migraine, 200 respondents knew a person who experienced migraines, and 300 members of the community did not know anyone with migraines. Respondents who had given birth ranked the pain of their worst migraine higher than childbirth pain (8.6 vs 7.3 based on a scale of 1 to 10). Additionally, respondents with medically diagnosed migraines ranked their worst migraine pain (8.6) higher than pain associated with broken bones (7.0) and kidney stones (8.3). According to the report, people without migraines regularly underestimated the average migraine length (20.7 hours vs 31 hours) and pain. The average pain rating for a typical migraine determined by those without migraines was 6.2 compared with 7.1 by those with migraines. Among people with migraines, 91% indicated that people without migraines are not fully aware of the disease severity. Sixty-two percent also reported masking the full impact of their migraines when at school or work.

The reporting for those with migraine demonstrated their concerns with the effect of the condition on their lives. Some examples of this include the following24:
  • 54%: “I worry that people think I’m lazy because of the impact migraines have on my life and ability to perform tasks.”
  • 40%: “I have been told to ‘get over it’ when I am experiencing a migraine attack.”
  • 29%: “I sometimes feel like my job is in jeopardy because of migraines.”
  • 28%: “I have been made fun of for having migraines.”

Most people with migraines also indicated that their migraine attacks frequently interfere with work productivity and advancement, attending important events, and spending time with family and friends, resulting in the addition of more stress, which is a migraine trigger. These statistics highlight the stigma connected to and lack of awareness about migraines.

Migraine Pain Theories (vs Vascular Theory)

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