RxCe - Pharmacy Team's Role in Migraine Management Materials

AURA YOU READY: THE PHARMACY TEAM’S ROLE IN MIGRAINE MANAGEMENT

Faculty:

Kelsey Giara, PharmD, RPh

Kelsey Giara is a New Hampshire-based pharmacist and freelance medical writer. She writes about a variety of healthcare topics for various publications, with significant experience in continuing medical education, needs assessments, grant writing, and medical communications.

Pamela Sardo, PharmD, BS

Pamela Sardo, PharmD, BS, is a freelance medical writer and licensed pharmacist. She is the founder and principal at Sardo Solutions in Texas. Pam received her BS from the University of Connecticut and her PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, and managed health care responsibilities across a broad range of therapeutic classes and disease states.

Abstract

A migraine headache is more than just a bad headache. It is a chronic, disabling condition that places a heavy burden on society. Theories of vasodilation or vasoconstriction as the root cause of migraine are outdated. Current theories suggest nerve cell-related issues lead to neurogenic inflammation. Many medications exist to prevent and treat migraines. Shared clinical decision-making and trial-and-error processes are needed to individualize treatment plans. Pharmacy teams should recognize signs of medication overuse headaches and the need for step-up care when prophylaxis is inadequate.

Accreditation Statements

In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation Council^TM for Continuing Medical Education (ACCME^®), the Accreditation Council for Pharmacy Education (ACPE^®), and the American Nurses Credentialing Center (ANCC^®), to provide continuing education for the healthcare team.

Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:

Pharmacists: JA4008424-0000-26-145-H01-P

Pharmacy Technicians: JA4008424-0000-26-145-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.

Credit Types:

Pharmacy - 2 Credits

Type of Activity: Application

Media: Computer-Based Training (i.e., online courses)

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Activity Pre-Test, Post-Test, and Activity Evaluation.

Release Date: July 3, 2026 Expiration Date: February 2, 2027

Target Audience: This educational activity is for Pharmacists and Pharmacy Technicians

How to Earn Credit: From July 3, 2026, through February 2, 2027, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Take the “Educational Activity Pre-Test;”

Study the section entitled “Educational Activity;” and

Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

CE Credits: Credits for this course will be uploaded to CPE Monitor^® for pharmacists and pharmacy technicians.

Statement of Need

Migraine headaches are chronic and disabling headaches that place a heavy burden on society. Many medications exist to prevent migraines from occurring and to treat them when they do. Pharmacy teams need to understand the treatment plans and their roles as members of an interdisciplinary team treating this patient population.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Discuss the prevalence and pathophysiology of migraine

Recognize unmet needs in migraine prevention and treatment

Identify red flags indicating inadequate migraine control and patients who would benefit from referral to a pharmacist or provider

Recognize storage requirements for agents in the CGRP therapeutic class

Disclosures

The following individuals were involved in planning, developing, and/or authoring this activity: L. Austin Fredrickson, MD, FACP; Ashley Walsh, PharmD; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.

Educational Activity Pre-Test

Which of the following BEST describes a migraine?

Bilateral, moderate-to-severe, constant pain accompanied by nausea

Unilateral, mild-to-moderate, constant pain accompanied by phonophobia

Bilateral, moderate-to-severe, pulsating pain accompanied by vomiting

Unilateral, moderate-to-severe, pulsating pain accompanied by nausea

A patient with chronic migraine is seeing flashing lights and experiencing muscle weakness, but they do not have any pain. Which phase of a migraine attack are they MOST LIKELY experiencing?

Premonitory symptoms

Prodrome or aura

Headache

Postdrome

Which of the following agents is appropriately matched to its description?

Ubrogepant is a small-molecule CGRP inhibitor nasal spray for acute migraine treatment

Lasmiditan is an mAb for acute migraine treatment targeting 5HT-1B and 5HT-1D receptors

Eptinezumab is a small-molecule oral tablet for migraine prevention targeting the CGRP protein directly

Fremanezumab is an mAb for migraine prevention targeting the CGRP protein to prevent binding

Educational Activity

Aura You Ready: The Pharmacy Team’s Role in Migraine Management

Introduction

Migraine headaches are chronic and disabling headaches that place a heavy burden on society. Newer theories have emerged citing neurogenic inflammation as the likely cause of these headaches. Many medications exist to prevent migraines from occurring and to treat them when they do. This course will discuss the clinical decision-making processes used to individualize treatment plans. Pharmacy teams are important members of the interdisciplinary team treating this patient population.

Prevalence and Impact of Migraine Headaches

Headaches, despite ranking among the most common disorders of the nervous system, are underestimated, under-recognized, and under-treated. They cause significant disability, often leading to decreased productivity and increased absenteeism (e.g., missing school or work days). Of all types of pain, headache is the most common; up to three-quarters of adults have had a headache in the last year.¹

Migraine—characterized by recurrent attacks of moderate-to-severe throbbing and one-sided pulsating pain—is the most common form of head pain, occurring more frequently than tension-type headache or sinus headache. About 15.3% of individuals in the United States, or 37 million people, suffer from migraine.² It most often begins at puberty with a peak incidence between ages 35 and 45 years and affects about twice as many women as men due to hormonal influences.¹

Migraine is more than just a bad headache; it can be debilitating, often leaving patients unable to perform daily functions. Among neurologic conditions, it ranks second worldwide based on years lost to disability.³ The condition is also the top cause of disability in adolescents and adults aged 15 to 49 years.⁴ This has a substantial societal impact, given that this is a time frame associated with high work productivity and family caregiving responsibilities. In fact, migraines cost the American healthcare system more than $17 billion annually in direct costs; indirect costs from lost productivity and reduced quality of life are significantly higher.⁵

Pathophysiology and Triggers

Migraine-associated pain is caused by activation of nerve fibers within the walls of brain blood vessels that travel within the meninges, the three membranes protecting the brain and spinal cord.⁶ Various pathways in the peripheral and central nervous systems are implicated in migraine development. The older vascular theory of migraine, which attributed headaches to vasodilation and auras to vasoconstriction, is no longer valid.⁷ Instead, current theories suggest that nerve cell-related issues are the root cause, leading to changes in the brain and the area surrounding it, which trigger migraines.

One of these changes is neurogenic inflammation, an inflammatory response initiated by the activation of nerve cells, specifically nociceptors, which are responsible for sensing and transmitting pain signals.⁸ This inflammation can also make the nerves more sensitive, which may explain why migraines can become more frequent and intense over time.⁹ Pain pathway stimulation and neurogenic inflammation also cause nerve cells to release neuropeptides implicated in migraine development, including serotonin and calcitonin gene-related peptides (CGRP).

Migraine most commonly strikes in the morning, especially upon waking.⁶ Many factors increase the risk of a migraine, and these triggers vary from person to person:⁶

Anxiety, depression, stress, or other strong emotions

Bright or flashing lights

Head trauma

Hormonal changes

Loud or sudden noises

Low blood sugar or skipped meals

Motion sickness

Overexertion

Poor sleep hygiene, including too much or not enough sleep

Strong odors or perfumes

Substance use, including tobacco, alcohol (hangover), or some medications

Sudden weather or environmental changes

For some, migraines are also predictable, occurring before menstruation or on a weekend after a particularly stressful week of work. Most people are symptom-free between attacks, but many feel exhausted or weak immediately following a migraine.⁶

Diagnosing Migraines

Treating migraine appropriately necessitates differentiation from other headache types. Table 1 lists common primary headache types and their defining features.

Table 1

Common Types of Primary Headache^10-13

Headache Type	Defining Features
Cluster headache	Severe pain that occurs around, behind, or above 1 eye Clustered 30-to-90-minute episodes 1 to 8 times daily for 1 day to several weeks at a time, separated by pain-free periods of months or years
Cough headache	Precipitated by a Valsalva maneuver* (e.g., coughing, sneezing, bending, straining, laughing) Pain is immediate, short-lived, and usually bilateral
Exertional headache	Precipitated by a sustained strenuous effort, with headache occurring during or after exertion Throbbing pain that can be accompanied by migraine features
Migraine headache	Moderate-to-severe throbbing, pulsating pain that is unilateral Sudden onset and pain lasting 4 to 72 hours May cause nausea, vomiting, and/or aura, and is aggravated by physical activity, light, and/or sound
New daily persistent headache	Sudden-onset headache that continues without remission for ≥ 24 hours May cause blurred vision, concentration problems, lethargy, light-headedness, neck stiffness, numbness/tingling, sleep disturbances, or vertigo
Stabbing headache	Transient and localized stabs of pain in the head that last up to a few seconds and occur spontaneously from one to many times daily Also known as ice pick pains, jabs and jolts, needle-in-the-eye syndrome, and sharp, short-lived head pain
Tension headache	Mild-to-moderate diffuse ache, tightening, pressing, and constricting pain that is bilateral Gradual onset and pain lasting 30 minutes to 7 days May cause scalp tenderness, neck pain, and/or muscle tension, and is aggravated by stress or anxiety
Thunderclap headache	Sudden, severe, explosive onset headache within seconds to minutes May be indicative of subarachnoid hemorrhage

*Attempted exhalation against a closed airway

Migraine Presentation

Migraine is a chronic condition causing recurrent attacks anywhere from once yearly to once weekly.¹ Patients typically have sudden onset of pain, and they present with at least two of the following criteria:^1,6

Moderate-to-severe head pain

Unilateral (one-sided) pain

Pulsating pain quality

Aggravation of pain by usual physical activity

A migraine may last four to 72 hours when untreated.^1,6

Nausea, vomiting, photophobia (light sensitivity), or phonophobia (sound sensitivity) must accompany a migraine episode.⁶ Routine physical activity, movement, or even coughing or sneezing can aggravate these symptoms. Children tend to suffer from migraine attacks that are of shorter duration with more prominent abdominal symptoms.¹

All patients experience migraine differently, adding even more challenges to diagnosis and treatment. Four possible phases of a migraine attack exist:⁶

Premonitory symptoms: up to 24 hours before developing migraine; possible symptoms include food cravings, unexplained mood changes (depression or euphoria), uncontrollable yawning, fluid retention, or increased urination

Prodrome/aura: immediately before or during migraine; possible symptoms include seeing flashing/bright lights or what looks like heat waves, muscle weakness, or the sensation of being touched or grabbed

Headache: pain starts gradually and builds in intensity; it is possible to have a migraine without a headache

Postdrome: feeling exhausted or confused may last up to a day before feeling healthy again

Migraine can occur with or without aura. Migraine without aura, or “common migraine,” is more common, occurring in about two-thirds of people.^2,6 In this case, headache pain occurs without warning on one side of the head, accompanied by nausea, confusion, blurred vision, mood changes, fatigue, and increased sensitivity to light or sound.⁶

Patients experiencing migraine with aura—previously coined “classic migraine”—have visual, sensory, speech, language, or motor disturbances that appear about 10 to 60 minutes before the headache starts and last no more than one hour.⁶ Visual manifestations are most common; about 95% of patients with aura describe perceptions of flashing, shimmering, or blind spots.² Some individuals may also temporarily lose part of or all their vision during an aura. Other possible symptoms include the following:⁶

trouble speaking

one-sided numbness, muscle weakness, or other abnormal sensation

tingling in the hands or face

confusion

nausea or loss of appetite

photophobia or phonophobia

visual or auditory hallucinations

Aside from typical migraine with or without aura, migraine headaches may include the following types:⁶

Abdominal migraine: moderate to severe pain in the middle of the abdomen lasting one to 72 hours with little or no headache, often accompanied by nausea, vomiting, and loss of appetite; mostly affects young children, but many will go on to develop migraine headaches later in life

Basilar-type migraine: throbbing pain comes on suddenly on both sides of the back of the head, accompanied by partial or total loss of vision or double vision, dizziness and loss of balance, poor muscle coordination, slurred speech, a ringing in the ears, and fainting; mainly affects children and adolescents, especially adolescent girls (associated with the menstrual cycle)

Hemiplegic migraine: rare, severe form of migraine that causes temporary one-sided paralysis for up to several days prior to or during a headache, which may be preceded by vertigo, a pricking or stabbing sensation, and problems seeing, speaking, or swallowing; may be caused by genetic mutations that make the brain more sensitive or excitable

Menstrual migraine: migraine without aura, pulsing pain on one side of the head, nausea, vomiting, and increased sensitivity to sound and light; affects women around the time of menstruation, but most will also have migraines at other points in their cycle

Migraine without headache: visual problems or other aura symptoms, nausea, vomiting, and constipation, but without head pain

Ophthalmoplegic migraine: head pain, along with a droopy eyelid, large pupil, and double vision that may last for weeks, long after the pain is gone; uncommon

Retinal migraine: attacks of visual loss or disturbances in one eye, typically associated with migraine headaches

Status migrainosus: rare, severe type of acute migraine causing disabling pain and nausea for 72 hours or longer; may be so intense that it requires hospitalization

Migraine Treatment

Providers treat migraine with acute treatments, preventive treatments, or both. However, the severity, frequency, and characteristics of migraine vary from person to person and even within the same individual over time, presenting challenges for optimizing treatment. As a result, a trial-and-error process is often needed before an individualized management plan is established.

The discovery of drugs targeting CGRP has introduced a new era for the migraine treatment landscape. Since 2018, four anti-CGRP monoclonal antibodies (mAbs) and four small-molecule CGRP antagonists, referred to as “gepants,” have been developed for migraine prophylaxis and/or treatment. Pharmacists should be well informed about available CGRP-targeting therapies, including which ones are indicated for prevention and which are for treatment of acute migraine.

Acute Migraine Treatment

Acetaminophen and NSAIDs

NSAIDs—aspirin, diclofenac, ibuprofen, and naproxen—are considered first-line therapy for mild-to-moderate migraine.⁵ Medication choice should be based on availability and adverse effect profile. Ibuprofen is typically a preferred agent given its widespread OTC availability and good tolerability, but it does have a short half-life, often necessitating repeat dosing.⁵ Patients should take 400 mg of ibuprofen for acute migraine treatment. Diclofenac is equally effective and is available as a tablet or powder formulation, but only via prescription. Naproxen is another viable option for patients suffering from acute migraine. It has a slower onset of action but a longer half-life, eliminating the need for repeated dosing. Patients typically take 500 mg of naproxen to treat migraine, but 825 mg may be slightly more effective.⁵

Aspirin is effective at doses of 1,000 mg but carries the greatest risk of gastric irritation.⁵ The combination of acetaminophen/aspirin/caffeine also has strong evidence of effectiveness and can be used as a first-line treatment for migraine, especially for patients with contraindications to vasoconstricting medications.⁵ Acetaminophen is less effective than NSAIDs but does not cause gastric irritation or antiplatelet effects. The recommended dose to treat migraine is 1,000 mg.⁵

Triptans

Triptans—including almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan—are considered first-line treatment for moderate-to-severe migraine.⁵ Unlike NSAIDs and acetaminophen, these agents are pharmacologically specific to migraine treatment as they are agonists at 5-hydroxytryptamine (5-HT; serotonin) receptors. While all triptans share the same mechanism of action, they differ in routes of administration, cost, and pharmacokinetics, as explained further in Table 2. Providers should individualize medication choices to the patient’s needs.

Table 2

Comparing Triptan Medications for Migraine⁵

Drug	Formulation	Half-Life (hours)
Almotriptan	Oral tablets	3 to 4
Eletriptan	Oral tablets	4
Frovatriptan	Oral tablets	26
Naratriptan	Oral tablets	6
Rizatriptan	Oral tablets ODT	2 to 3 2 to 3
Sumatriptan	Oral tablets SC injection Nasal spray	2.5 2.5 2
Zolmitriptan	Oral tablets ODT Nasal spray	3 3 3

ODT, orally disintegrating tablets; SC, subcutaneous

Few head-to-head studies are available comparing the seven triptan medications, but the strongest evidence and most favorable outcomes are reported for sumatriptan subcutaneous injection, rizatriptan orally disintegrating tablets (ODT), zolmitriptan ODT, and eletriptan tablets.⁵ A systematic review analyzing the effectiveness of the seven available triptans found that standard doses provided headache relief for 42% to 76% of patients and complete pain relief for less than half of patients at two hours.¹⁴ This was better than NSAIDs, acetaminophen, or ergot alkaloids (e.g., dihydroergotamine, ergotamine) alone but equal to or slightly worse than triptans combined with NSAIDs or acetaminophen.

Unfortunately, triptans fall short for many; up to 30% of patients do not respond to this medication class.¹⁵ Notably, repeating the same dose of the same triptan may not relieve persistent migraine symptoms, but if the migraine resolves and then recurs within 24 hours, the initial triptan is likely to be effective.⁵ Choosing a triptan with a longer half-life or combining the triptan with 500 mg of naproxen are useful strategies to reduce migraine recurrence rates. Triptans are generally well tolerated but contraindicated in patients with cardiovascular diseases, as they have potential vasoconstrictive effects on cerebral and coronary arteries.¹⁵

Gepants

A more recent addition to the migraine treatment armamentarium is the “gepants”—including rimegepant, ubrogepant, and zavegepant—which are small-molecule CGRP inhibitors. These are generally better tolerated than triptans and may be less likely to cause medication overuse headache (MOH), which accelerates migraine and additional complications due to overuse of breakthrough therapies.¹⁶ Overuse of acute treatments is defined as one of the following:³

10 or more days per month for ergot derivatives, triptans, opioids, combination analgesics, and a combination of drugs from different classes that are not individually overused

15 or more days per month for nonopioid analgesics, acetaminophen, and NSAIDs

Patients take 75 mg of rimegepant orally as needed for acute migraine treatment.¹⁷ Studies have not established the safety of using more than 18 doses in a 30-day period.¹⁵ Rimegepant is supplied as an ODT formulation, so patients can swallow it without additional liquid. This makes it an attractive option for people who are often on the go, as well as those who suffer from migraine-associated nausea. Rimegepant is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2C9, presenting ample opportunity for drug interactions that should be mitigated by a pharmacist.^16,17

Ubrogepant is dosed 50 mg or 100 mg orally as needed for episodic migraine.¹⁸ If needed, patients can take another dose two hours after the initial dose for persistent symptoms, with a maximum dose of 200 mg in 24 hours. Clinical trials have not evaluated the safety of using ubrogepant to treat more than 8 migraines in 30 days.¹⁶ Ubrogepant is mainly metabolized through CYP3A4, so pharmacists should be cognizant of watching for inhibitors or inducers of the enzyme.^16,18

Zavegepant is the first CGRP antagonist nasal spray for abortive migraine treatment.^19,20 This presents a fast-relief option, especially for patients suffering from migraine-associated nausea or vomiting who require non-oral treatment. Although head-to-head studies are lacking, zavegepant should offer favorable safety and tolerability compared with triptan nasal sprays, given its absence of cardiovascular contraindications and precautions and its reduced risk of MOH.¹⁹ In clinical trials, depending on dose, up to 61.2% of patients taking zavegepant had pain relief, and up to 34.7% had returned to normal function at 2 hours post-dose.²¹ Importantly, 26.5% and 49.8% had pain relief at 30 and 60 minutes, respectively, and 44.5% and 38.8% sustained pain relief at 24 and 48 hours post-dose. This suggests fast onset and sustained relief for patients with acute migraine with or without aura.

Ditans

“Ditans” are another newer option for the treatment of acute, moderate-to-severe migraine. Like “triptans,” ditans also bind to serotonin receptors, but the subtypes these medications target are different.²² Triptans bind to 5-HT1B and 5-HT1D receptor subtypes, while ditans bind to the 5-HT1F receptor subtype.

5-HT1B/1D receptors are localized in blood vessels, especially in the cerebral and coronary systems.²² Targeting these subtypes mediates several mechanisms related to migraine pathophysiology, including the following:²²

vasoconstriction of pain-dilated cerebral vessels

reduction of nerve activation resulting in inhibition of the release of inflammatory peptides (including CGRP) by trigeminal nerves

inhibition of pain neurotransmission

Unfortunately, targeting these receptor subtypes may also induce vasoconstriction in coronary arteries, which is dangerous in patients with underlying heart conditions.²² Ditans, as selective agents for the 5-HT1F receptor subtype, have very low affinity for 1B/1D receptors, thereby preventing vasoconstriction and making them safer in patients with cardiac conditions.

Lasmiditan was the first in this class of medications to receive FDA approval for acute migraine treatment in October 2019. In clinical trials, patients receiving 60 mg or 200 mg had higher headache response rates than placebo. Patients who took 60 and 200 mg had improved 2-hour headache response rates (50% vs 71%), were more likely to be pain-free after 2 hours (27% vs 38%), and achieved higher sustained headache response rates (37% vs 52%).²³ Additionally, 20% sustained pain relief 24 hours after treatment.

Despite its increased safety in patients with cardiovascular diseases, this drug class does carry a risk of lowering heart rate in patients already taking heart rate-lowering drugs and can cause dizziness, sleepiness, and tiredness.²⁴ People should not drive for at least 8 hours after a dose, which can limit lasmiditan’s use. Preliminary evidence shows that MOH is likely a concern with ditans, but further investigation is needed.¹⁵

Migraine Prophylaxis

Nearly 40% of migraine sufferers require preventive therapy based on monthly headache days and associated levels of impairment, but only 3% to 13% currently use it.²⁵ The goals of migraine prevention include the following:³

reducing attack frequency, severity, duration, and associated disability

improving responsiveness to and avoiding escalated use of acute treatments

reducing reliance on poorly tolerated, ineffective, or unwanted acute treatments

reducing the overall cost associated with migraine treatment

enhancing patients’ autonomy in managing their own disease

reducing headache-related distress and psychological symptoms

improving health-related quality of life

Although one might expect that patients who are afflicted with pain would be adherent to treatment, data suggest otherwise. Research indicates that at 2 months, treatment persistence falls to 50% in people who experience chronic migraine.²⁶ At six and 12 months, treatment persistence falls to 25% and 14%, respectively. Of patients who discontinue their prophylactic regimen, 23% switch to a different prophylactic drug, and 41% re-initiate therapy within one year. Unfortunately, among those who switch, less than 13% remain on prophylactic therapy for one year.²⁶

Pharmacists and pharmacy technicians play a significant part in identifying migraineurs who would benefit from preventive therapies and encouraging adherence to prescribed regimens. Red flags indicating a need for prophylaxis include migraine attacks that significantly interfere with daily routines despite treatment; frequent attacks; contraindication to, failure, or overuse of acute treatments; and adverse effects with acute treatments.³ Eligibility for preventive treatment depends upon both frequency and degree of disability, as shown in Table 3.

Table 3

Eligibility Criteria for Migraine Prophylaxis³

Degree of Disability*	Monthly Headache Days	Recommendation
None	≥ 6	Offer prevention
None	4 or 5	Consider prevention
Some	≥ 4	Offer prevention
Some	3	Consider prevention
Severe	≥ 3	Offer prevention
Severe	2	Consider prevention

*Measured by the Migraine Disability Assessment Scale, Migraine Physical Function Impact Diary, or Headache Impact Test

When initiating preventive therapy, start with the lowest effective dose and titrate it every two to four weeks until effectiveness is achieved without adverse effects.²⁷ It may take up to 6 months to see full effectiveness, but if patients experience no change after two months, providers should consider a therapy change. Realistic goals for prevention include the following:

50% reduction in the number of attacks

significant decrease in attack duration

improvement in response to acute therapy

If patients’ migraines remain well controlled for at least six to 12 months, consider a slow taper and discontinuation.²⁷

Traditional Prophylaxis

Until recently, no drugs were specifically developed for migraine prevention, and providers prevented migraines by repurposing medications for other indications. Traditional therapies for migraine prevention—beta blockers, antidepressants, and anticonvulsants—are often inadequate. They have limited to moderate efficacy, moderate to high rates of adverse effects, contraindications, and interactions that limit use.³

The most commonly used drug class for migraine prevention is beta blockers, including atenolol, metoprolol, nadolol, propranolol, and timolol.²⁷ Common adverse effects include bradycardia, depression, erectile dysfunction, fatigue, hypotension, lethargy, and nightmares. Providers should consider them for patients with hypertension, angina, or ischemic heart disease. Patients with asthma, atrioventricular conduction defects, bradycardia, or chronic obstructive pulmonary disease should not use beta blockers for migraine prevention.

Amitriptyline, an antidepressant, is an effective therapy for migraine prevention. However, it carries a high risk of adverse effects, most commonly sedation and dose-related anticholinergic effects (e.g., blurry vision, constipation, dry mouth, palpitations, tachycardia, and urinary retention).²⁷ Cardiac condition abnormalities, orthostatic hypotension, QT prolongation, and weight gain are also possible. Amitriptyline is a good choice for treating patients with concomitant depression or insomnia, but higher doses are needed to adequately address depression than those traditionally used for migraine prevention.²⁷

Anticonvulsants are another medication class often used to prevent migraine, commonly divalproex or topiramate.²⁷ Divalproex is a valuable option for migraine prevention in patients with comorbid seizure disorders or bipolar disorder. It commonly causes gastrointestinal distress, nausea, somnolence, and vomiting, and tremors and alopecia are possible later in therapy. Topiramate can treat seizure disorders and migraines concomitantly as well. It most commonly causes paresthesia (numbness/tingling), abdominal pain, fatigue, impaired memory and concentration, and weight loss.²⁷

Anti-CGRP Preventives

Some gepants—atogepant and rimegepant—are approved for migraine prevention. Patients take atogepant 10 mg, 30 mg, or 60 mg by mouth daily or rimegepant 75 mg by mouth every other day to prevent migraines.^17,28 It is important to note that patients cannot take additional rimegepant for breakthrough migraine.¹⁷

Anti-CGRP mAbs approved for migraine prevention include eptinezumab, fremanezumab, galcanezumab, and erenumab.^27,29-32 Erenumab targets the CGRP receptor directly, while other mAbs (e.g., fremanezumab) attach to the CGRP protein itself to prevent it from binding to its receptor. A healthcare provider administers eptinezumab intravenously every three months while patients self-administer the other three subcutaneously (SC) monthly to quarterly, depending on the agent:

Erenumab 70 mg or 140 mg SC monthly²⁷

Fremanezumab 225 mg SC monthly or 675 mg SC every 3 months³⁰

Galcanezumab 240 mg SC once, then 120 mg SC monthly³¹

Monthly or quarterly administration of these agents, rather than a daily pill, can improve patient adherence. Anti-CGRP mAbs have good efficacy, safety, and tolerability, making them an attractive option for patients with frequent, episodic, and chronic migraine.

The Pharmacy Team’s Role

The entire pharmacy team can help patients with migraines. A well-documented fact is pharmacy team accessibility. Patients visit the pharmacy considerably more often than they visit their prescribers. On average, Americans visit a pharmacy 35 times annually.³³ This statistic is critical for patients who live in rural areas, where they may not have access to a neurologist. About 90% of Americans live within five miles of a pharmacy, making pharmacists the most accessible healthcare professionals and perfectly positioned to improve care for travel-restricted, underserved patients.³⁴

Pharmacy Technicians

Watch for Red Flags, Know Storage Requirements

Often, pharmacy technicians know their customers well. When patients report headaches lasting more than a few days or numbness or tingling in other areas of their bodies, it is time to involve the pharmacist.³² If patients report a headache that starts extremely quickly and is very painful, they need emergency care. If patients report neck stiffness, changes in headache intensity across positions, or recent intensification of pain or frequency, these, too, are red flags and require immediate assessment.³²

With the numerous medications now used to prevent and treat migraine, patients will need to know how to store them. In particular, medications that require refrigeration. Technicians need to make sure that patients have accurate information about storing the CGRP injectables and that they know if temperature excursions are allowed:

Eptinezumab: Store refrigerated 36°F to 46°F in the original carton to protect from light until time of use. Do not freeze or shake.²⁹

Erenumab: Store refrigerated 36°F to 46°F in the original carton to protect from light until time of use. If removed from the refrigerator, keep at room temperature (up to 77°F) in the original carton and use within 7 days. Do not freeze or shake.²⁷

Fremanezumab: Store refrigerated 36°F to 46°F in the original carton to protect from light until the time of use. If removed from the refrigerator, keep it at room temperature (up to 86°F) in the original carton and use it within 7 days. Do not freeze or shake.³⁰

Galcanezumab: Store refrigerated 36°F to 46°F in the original carton to protect from light until the time of use. If removed from the refrigerator, keep it at room temperature (up to 86°F) in the original carton and use it within 7 days. Do not freeze or shake.³¹

Pharmacists

Quick, Thorough Assessment

When patients ask for advice about headaches, the goal is to differentiate between tension, sinus, and migraine headaches. Pharmacists’ work with patients who have or may have migraine begins with careful questioning. Questions should elicit information about headache history, symptom type, severity, frequency, and triggers (if they are aware of triggers). It can also be helpful to encourage patients to develop and maintain a headache diary that tracks aggravating and remitting factors, as well as their analgesic use. Regarding analgesic use, pharmacists need to look at patterns and be alert for signs of MOH.

After collecting this information, pharmacists can make an appropriate assessment and recommendation and provide patient education. For mild-to-moderate migraine, acetaminophen and NSAIDs are helpful. Many patients start with an OTC NSAID, and a key counseling point is to limit the use of these analgesics to 2 days per week to avoid MOH. In particular, pharmacists need to manage patients’ expectations, so they have realistic ideas about treatment outcomes.

If patients need OTC analgesics for more than 2 days a week or they experience ongoing poor quality of life (e.g., missing work or school, inability to socialize, confinement to bed), referral to a prescriber is the next step for further evaluation. At this point, a different medication is likely to be more effective. In many cases, preventive medications can help, and pharmacists need to stress adherence. With some treatments, patients may have cost or insurance issues. Pharmacists and technicians can help patients find patient assistance programs or navigate prior authorization.

Pharmacists must also screen for drug interactions. For the triptan class, the cytochrome P450 3A4 isoenzyme is a primary concern; interactions with azole antifungals, macrolide antibiotics, and some antiretroviral therapies are predictable and preventable depending on the triptan being used. Additionally, sumatriptan, zolmitriptan, and rizatriptan are metabolized by monoamine oxidase. Only rizatriptan has a significant warning to limit its dose to 5 mg (as opposed to 10 mg) and to three doses in any 24-hour period with propranolol, a common migraine prophylaxis drug.³⁵

Monitoring for adverse effects and adherence issues is also a pharmacist's responsibility. Including a section in the headache diary to record the date, time, strength, and response to a dose of medication can help improve adherence to preventive medications and identify what works and what does not. Strategies used to improve adherence in other conditions—pill boxes, reminders, alarms, etc.—also work in migraine.

Counseling should be tailored to individual patients. With all medications, counseling should include how and when to take the medication, what to do if a dose is missed, and potential adverse effects. Patients will need additional counseling when they start injectables, and the pharmacy team must ensure they have clear written instructions to take home after the pharmacist reviews the injection technique. Patients can also be referred to organizations such as the National Headache Foundation³⁶ at https://headaches.org/ or the American Headache Society³⁷ at https://americanheadachesociety.org for additional support or resource materials.

Finally, undertreatment is widespread. Patients may need encouragement to see a prescriber and step up treatment. Explaining that preventive treatments are available and that sometimes, it is time to try a different approach can prompt patients to try new, more effective treatments.

Summary

Migraine headache is the most common form of head pain, and many therapies exist for migraine prevention and treatment, all with benefits and shortcomings. Pharmacists and pharmacy technicians likely interact with individuals with migraine regularly, necessitating that they be able to distinguish it from other headache disorders and ensure patients are treated appropriately and thoroughly.

References

World Health Organization. Headache disorders fact sheet. April 8, 2016. https://www.who.int/en/news-room/fact-sheets/detail/headache-disorders. Accessed December 21, 2023.

Burch R. Migraine and tension-type headache: Diagnosis and treatment. Med Clin North Am. 2019;103(2):215-233.

Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi:10.1111/head.14153

López-Bravo A, Oliveros-Cid A, Sevillano-Orte L. Treatment satisfaction with calcitonin gene-related peptide monoclonal antibodies as a new patient-reported outcome measure: A real-life experience in migraine. Acta Neurol Scand. 2022;145(6):669-675.

Mayans L, Walling A. Acute migraine headache: Treatment strategies. Am Fam Physician. 2018;97(4):243-251.

National Institute of Neurological Disorders and Stroke. Migraine. Updated July 11, 2023. https://www.ninds.nih.gov/health-information/disorders/migraine. Accessed December 21, 2023.

Amin FM, Asghar MS, Hougaard A, et al. Magnetic resonance angiography of intracranial and extracranial arteries in patients with spontaneous migraine without aura: a cross-sectional study. Lancet Neurol. 2013;12(5):454-461. doi:10.1016/S1474-4422(13)70067-X

Matsuda M, Huh Y, Ji RR. Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth. 2019;33(1):131-139. doi:10.1007/s00540-018-2579-4

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Wedro B, Taylor DC. Headache. Reviewed December 14, 2023. https://www.medicinenet.com/headache/article.htm. Accessed January 17, 2024.

Bahra A. Other primary headaches-thunderclap-, cough-, exertional-, and sexual headache. J Neurol. 2020;267(5):1554-1566. doi:10.1007/s00415-020-09728-0

Yamani N, Olesen J. New daily persistent headache: a systematic review on an enigmatic disorder. J Headache Pain. 2019;20(1):80. Published 2019 Jul 15. doi:10.1186/s10194-019-1022-z

Murray D, Dilli E. Primary stabbing headache. Curr Neurol Neurosci Rep. 2019;19(7):47. Published 2019 Jun 8. doi:10.1007/s11910-019-0955-6

Cameron C, Kelly S, Hsieh SC, et al. Triptans in the Acute Treatment of Migraine: A Systematic Review and Network Meta-Analysis. Headache. 2015;55 Suppl 4:221-235.

Lo Castro F, Guerzoni S, Pellesi L. Safety and Risk of Medication Overuse Headache in Lasmiditan and Second-Generation Gepants: A Rapid Review. Drug Healthc Patient Saf. 2021;13:233-240.

Rissardo JP, Caprara ALF. Gepants for Acute and Preventive Migraine Treatment: A Narrative Review. Brain Sci. 2022;12(12):1612. doi:10.3390/brainsci12121612

Nurtec ODT (prescribing information). Biohaven Pharmaceuticals Inc.; 2022.

Ubrelvy (prescribing information). Allergan; 2023.

Meglio M. FDA Accepts New Drug Application for Intranasal Zavegepant to Treat Acute Migraine. May 24, 2022. https://www.neurologylive.com/view/fda-accepts-new-drug-application-intranasal-zavegepant-treat-acute-migraine. Accessed January 16, 2024.

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Aimovig (prescribing information). Amgen; 2022.

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American Migraine Foundation. Changes in headache symptoms: When to be concerned. May 23, 2019. https://americanmigrainefoundation.org/resource-library/changes-in-headache-symptoms-concerned/. Accessed January 8, 2024.

Gebhart F. Pharmacists want more time with patients. Drug Topics. March 18, 2019. https://www.drugtopics.com/view/pharmacists-want-more-time-patients. Accessed January 16, 2024.

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DISCLAIMER

The information provided in this course is general in nature, and it is designed solely to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.

Healthcare professionals must consult their employer, healthcare facility, hospital, or other organization for guidelines, protocols, and procedures to follow. The information provided in this course does not replace those guidelines, protocols, and procedures, but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.

Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses is constantly changing. Any person taking this course understands that such a person must make an independent review of medication information before any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.

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