A Case of Severe Monthly Headaches in Teacher: Workup and Treatment

A35-year-old Black woman presents to the emergency department (ED) with a severe headache around her right temple and eye, which is accompanied by nausea, light sensitivity, and mental fog. She is a high school teacher and her headache began suddenly about 3 hours earlier while she was giving a presentation to her colleagues. She describes the pain as throbbing, severe, constant, and disabling. She denies having fever, motor weakness, or problems with gait and balance.

The patient has experienced this type of headache since the age of 12 years. Her mother suffered from similar headaches when she was younger.The patient was diagnosed with menstrual migraines at the age of 25 years and was told to take ibuprofen as needed. Her headaches have significantly increased in frequency in the last year while she was completing graduate school studies. She thinks the headaches are an “occupational hazard” as most teachers she works with experience headaches.

The headaches usually start suddenly, 2 days before her menstrual cycle, and last from several hours to 2 to 3 days if not treated.The headaches are associated with nausea and light sensitivity 80% of the time. The patient notes that she has 2 to 4 headache days a month that are not associated with her menstrual cycle.

She has been to the ED on 3 occasions for migraines in the last year. Medication history includes ibuprofen, which she notes works only 30% to 50% of the time, and topiramate, which she stopped after a week because of significant cognitive side effects and inability to focus at work. Her primary care physician (PCP) told her she cannot take propranolol because of her history of asthma but said that the headaches will subside when she goes through menopause. She has not tried any other preventive agents. Diagnostic workup prior to this visit included a computed tomography (CT) scan and magnetic resonance imaging (MRI), both of which were negative for other secondary causes of headache (eg, tumors, bleeding, infections).

Discussion

Migraine is a chronic neuroinflammatory disorder that occurs across a patient’s lifespan. Patients can experience episodic exacerbations and age-dependent changes in clinical presentation and prevalence. Migraine affects approximately 15% of the US population1,2 and is more common than type 1 diabetes, asthma, and epilepsy combined.3,4 According to the American Migraine Foundation, 1 in 4 American households have a person with migraines. Women have a 3-fold higher prevalence of migraine compared with men, with 30% of women experiencing migraines in their lifetime.3

Racial disparities in migraine diagnosis and management are also found. The American Migraine Foundation noted that only 47% of Black patients and 50% of Hispanic patients with headaches have an official headache diagnosis compared with 70% of White patients.5 Black patients with migraine also report higher pain intensity than White patients but are less likely to receive acute pain medication. Only 14% of Black patients receive prescriptions for acute migraine medications compared

TABLE 1. Pharmacotherapy for Migraine and Headache Treatment13

Generic Brand Dose

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

Rimegepant Nurtec ODT

Ubrogepant Ubrelvy

Zavegepant Zavzpret

Ergot Alkaloid

Dihydroergotamine mesylate

Migranal

Trudhesa

Adults: 75 mg once as needed (max daily dose). The safety of using more than 18 doses in a 30-day period has not been established. Children: not established.

Adults: Initially 50 mg or 100 mg tablet; may give a second dose ≥2 hrs after initial dose (max 200 mg/d). The safety of treating more than 8 migraines in a 30-day period has not been established. Children: not established.

Adults: Maximum dose 10 mg (1 spray) in 24-hour period. The safety of treating more than 8 migraines in a 30-day period has not been established. Children: Not established

Adults: 1 mL IV at 1 hr intervals; max 2 doses/day. Or, 1 mL IM or SC at 1 hr intervals; max 3 doses/day. For all: max 6 doses/wk. Not for chronic use. Children: not established.

Adults: 1 nasal spray in each nostril, repeat 15 mins later; max 6 sprays/24 hrs and 8 sprays/wk. Children: not established.

Adults: 1 nasal spray in each nostril, may repeat at least 1 hr later if needed; max 2 doses (4 sprays) within 24 hrs or 3 doses (6 sprays) within 7 days. Children: not established.

Ergotamine tartrate

Caffeine

Ergotamine tartrate

Caffeine

Adults: 2 tablets at onset of attack, then 1 tab every ½ hr if needed; max 6 tabs/attack, 10 tabs/wk. Children: not recommended.

Adults: 1 rectal suppository at onset of attack, then 1 supp after 1 hr if needed; max 2 supps/attack, 5 supps/wk. Children: not recommended.

Non-Steroidal Anti-inflammatory (NSAID)

Celecoxib Elyxyb

Adults: 120 mg (4.8 mL) oral solution. Max: 120 mg/d. Use for the fewest number of days per month, as needed. Moderate hepatic impairment, CYP2C9 poor metabolizers: max 60 mg (2.4 mL). Children: not established.

Diclofenac potassium Cambia ≥18 yrs: Mix 1 packet (50 mg) with 30–60 mL of water only and drink immediately. Packet contains phenylalanine. Not interchangeable with other forms of diclofenac. <18 yrs: not recommended.

Ibuprofen Advil Migraine ≥18 yrs: Usually 400 mg once daily. Max 2 caps/24 hrs. <18 yrs: consult physician.

Selective 5-HT1B/1D Receptor Agonist

Almotriptan (as malate)

≥12 yrs: 6.25–12.5 mg single dose tablets; may repeat once after 2 hrs; max 25 mg/24 hrs. Hepatic impairment, CrCl 10–30 mL/min, or concomitant potent CYP3A4 inhibitors: initially 6.25 mg once; max 12.5 mg/24 hrs. The safety of treating an average of more than 4 migraines over 30 days is not established. <12yrs: not established.

Eletriptan HBr Relpax ≥18 yrs: one 20 mg or 40 mg tablet; max single dose: 40 mg. May repeat once after 2 hrs; max 80 mg/day. The safety of treating an average of more than 3 headaches in a 30-day period has not been established. <18 yrs: not established.

Frovatriptan (as succinate)

Frova ≥18 yrs: 2.5 mg tablet with fluids; may repeat once after 2 hrs; max 7.5 mg/24 hrs. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Naratriptan HCl Amerge ≥18 yrs: 1 mg or 2.5 mg tablet with fluids; may repeat once after 4 hrs; max 5 mg/24 hrs. The safety of treating, on average, more than 4 headaches in a 30-day period has not been established. Mild-to-moderate renal/hepatic impairment: initially 1 mg; max 2.5 mg/24 hrs. <18 yrs: not recommended.

Rizatriptan (as benzoate)

Maxalt ≥18 yrs: Initially 5 mg or 10 mg tablet or ODT; may repeat after 2 hrs; max 30 mg/24 hrs. Concomitant propranolol: 5 mg; max 15 mg/24 hrs.The safety of treating, on average, more than 4 headaches in a 30-day period has not been established. <6 yrs: not established. 6–17yrs (<40 kg): 5 mg; (≥40 kg): 10 mg. Concomitant propranolol (≥40 kg only): max 5 mg/24 hrs. The efficacy and safety of treating with ≥1 dose/24 hrs have not been established. ODT contains phenylalanine.

Maxalt-MLT with 37% of White patients.5 Migraines impose a substantial direct and indirect financial burden.The combined cost of direct medical expenses and lost productivity from migraines is $20 million in the US alone.3 On average, a person with migraine misses 9 workdays annually because of their condition.6

Migraine is one of the most common and debilitating diseases encountered by primary care providers (PCPs).4 Primary care is the predominant site for migraine consultation and management for 70.3% of patients, and migraine accounts for 5 to 9 million PCP office visits annually in the US.1,7 Most patients (73.5%) who present with migraine symptoms to a PCP are not referred to a neurologist and remain in primary care.8

Disease Course and Treatment

Migraines are often undiagnosed and undertreated.The understanding of migraines shifted in the late 1990s.9-11 Modern understanding of migraine pathophysiology radically changed the migraine treatment paradigm, ushering in a new era of migraine-specific therapies such as 5-hydroxytryptamine 1F (5-HT1F) receptor agonists and calcitonin gene-related peptide (CGRP) receptor antagonists (Table 1).12,13 Neuromodulatory devices approved by the Food and Drug Administration (FDA), including Cefaly, Nerivio, and Relivion, are guideline-recommended for acute treatment of migraines and gammaCore is approved to treat and prevent migraines in people older than age 12 years.14 As with any chronic disease, migraine prevention is the cornerstone of migraine management.15 Episodic migraine (EM) is 0 to 14 headache days per month and chronic migraine (CM) is 15 or more headache days per month.16

The American Headache Society (AHS) recommends migraine preventive management for patients with 6 or more migraine headache days per month.14 The AHS guidance outlines strategies for optimal drug selection of preventive treatment and agents with established efficacy in migraine

TABLE 1. Pharmacotherapy for Migraine and Headache Treatment13

Generic Brand Dose

Selective 5-HT1B/1D Receptor Agonist (continued)

Sumatriptan Imitrex Injection ≥18 yrs: 6 mg SC (may start at lower dose if 6 mg not tolerated). May repeat after 1 hr; max two 6 mg doses in 24 hrs. <18 yrs: not recommended.

Imitrex Nasal Spray ≥18 yrs: One 5 mg, 10 mg, or 20 mg nasal spray. May repeat dose once after 2 hrs; max 40 mg/day. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Imitrex Tablets ≥18 yrs: 25–100 mg once, swallow tablet whole with fluids as soon as possible after migraine onset; may repeat dose at intervals of at least 2 hrs, max 200 mg/day; or single-dose tablets up to 100 mg/day if injection has been used. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Onzetra Xsail ≥ 18 yrs: One nosepiece (11mg) in each nostril (22 mg total), using Xsail delivery device. May repeat once after ≥ 2 hrs; max 44 mg (4 nosepieces)/day or one dose of Onzetra Xsail and one dose of another sumatriptan product separated by ≥ 2 hrs. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not established.

Tosymra ≥18 yrs: 10 mg as single nasal spray in one nostril. Reevaluate if no response. Max cumulative dose: 30 mg in 24 hrs with each dose separated by ≥1 hr. May also be given ≥1 hr after another sumatriptan product. <18 yrs: not recommended.

Zembrace Symtouch ≥18 yrs: 3 mg SC. May repeat after ≥1 hr; max 12 mg in 24 hrs. May also be given ≥1 hr after another sumatriptan product. <18 yrs: not recommended.

Zomig-ZMT

Zolmitriptan Zomig ≥18 yrs: Initially 1.25–2.5 mg tablets or ODT; max recommended single dose: 5 mg. If headache returns, may repeat after 2 hrs; max 10 mg/day. The safety of treating an average of more than 3 headaches in a 30-day period has not been established. Hepatic impairment (moderate to severe): 1.25 mg; (severe): max 5 mg/day. Concomitant cimetidine: max single dose: 2.5 mg, not to exceed 5 mg in 24 hrs. <18 yrs: Not recommended. ODT contains phenylalanine

Zomig Nasal Spray ≥12 yrs: Initially 2.5 mg nasal spray used once; max single dose: 5 mg. If headache returns, may repeat once after 2 hrs; max 10 mg/day. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. Moderate to severe hepatic impairment: not recommended; use other forms. Concomitant cimetidine: max single dose: 2.5 mg, not to exceed 5 mg in 24 hrs. <12 yrs: Not established.

Selective 5-HT1B/1D Receptor Agonist + Non-Steroidal Anti-Inflammatory (NSAID)

Sumatriptan succinate/naproxen sodium

Treximet ≥12 yrs: 1 tablet (85/500 mg) once; may repeat once after 2 hrs; max 2 tablets/day. Mild-to-moderate hepatic impairment: 1 tab (10/60 mg)/day. The safety of treating an average of more than 5 migraines in a 30-day period has not been established. <12 yrs: Not established. 12–17 yrs: 1 tablet (10/60 mg) once; max 1 tablet (85/500 mg) a day. The safety of treating an average of more than 2 migraines in a 30-day period has not been established.

Selective 5-HT1F Receptor Agonist

Lasmiditan Reyvow Adults: 50–200 mg tablets once as needed; max 1 dose/24 hrs. The safety of treating an average of >4 migraines in a 30-day period has not been established. Children: Not established.

Notes

IM, intramuscular; IV, intravenous; ODT, orally disintegrating tablets; SC, subcutaneous injection; soln, solution; supp, suppositories aTable is not an inclusive list of medications, official indications, and/or dosages. Please see drug monographs at eMPR.com, contact companies for full drug labeling and/or consult your health care provider. Reprinted with permission from eMPR.com.

prevention.14 The AHS also recommends considering use of neuromodulatory devices as an adjunct to the existing treatment plan for all patients requiring preventive treatment.14

Clinicians Need More Migraine Training

Despite the relatively high prevalence and morbidity associated with migraine, more than one-quarter of PCPs (28%) lack familiarity with the AHS recommendations and 53% fail to prescribe migraine preventive medications.17 The average gap between diagnosis and initiation of preventive medications is 4 years and the majority of patients with episodic migraines who meet criteria for preventive therapy are not prescribed treatments. Suboptimal migraine preventive management results in frequent office visits, increased disability, barbiturate and opioid overuse, absenteeism, and increased rates of urgent care and ED visits. The inadequate use of preventive management strategies is concerning given the high rates of

TABLE 2. Pharmacotherapy for Migraine Prevention13

Generic Brand Dose

PROPHYLAXIS

Antiepileptic Drugs

Divalproex sodium Depakote

Depakote ER

Topiramate Topamax Capsules

Topamax

Eprontia migraine-related disability and high percentage of ED visits with migraine as the chief complaint (25%).18

No standardized approach exists for teaching headache medicine in medical school, PA, or nurse practitioner (NP) programs. Education in headache medicine varies from institution to institution. On average, less than 2 hours are dedicated to headache disorders in medical schools despite the very high prevalence of headache disorders in the general population. Most graduates do not receive the training needed to recognize and treat headache disorders during residency.17

The American Migraine Prevalence and Prevention (AMPP) study showed that PCPs are hesitant to prescribe migraine preventive medications because of the lack of understanding of AHS treatment guidelines and novel therapies.8

Another barrier is the lag time between publication and uptake in clinical practice. On average, it takes 17 years from the publication of research findings to implementation in clinical

Adults: Initially 250 mg delayed-release tablet twice daily; usual max 1 g/day. Elderly: reduce initial dose and titrate slowly; monitor. Concomitant rufinamide: initiate at a low dose and titrate. Children: Not recommended.

Adults: 500 mg extended-release tablet once daily for 1 week, then 1 g once daily. Elderly: reduce initial dose and titrate slowly; monitor. Concomitant rufinamide: initiate at a low dose and titrate. Children: Use other forms.

≥12 yrs: Titrate at 1-week intervals to target dose of 100 mg/day. Initially 25 mg once daily in the PM, then 25 mg twice daily, then 25 mg in the AM and 50 mg in the PM, then 50 mg twice daily. <12 yrs: Not established.

Adults: Initially 25 mg once daily in the PM, then 25 mg twice daily, then 25 mg in the AM and 50 mg in the PM, then to target dose 50 mg twice daily. Titrate at 1 wk intervals. Children: Not established.

Beta-Blockers

Propranolol

Timolol

Inderal LA

Adults: Initially 80 mg scored tablet daily in divided doses. Usual range: 160–240 mg/day. Discontinue if poor result after 4–6 wks. Children: Not recommended.

Adults: Initially 10 mg tablet twice daily. Increase weekly if needed; max 30 mg daily in 2 divided doses. Evaluate at 6–8 wks. Children: Not recommended.

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

Atogepant Qulipta

Eptinezumab-jjmr Vyepti

Erenumab-aooe Aimovig

Fremanezumab-vfrm Ajovy

Galcanezumab-gnlm Emgality

Adults: Episodic migraine: 10 mg, 30 mg, or 60 mg tablets once daily. Chronic migraine: 60 mg tablet once daily. Children: Not established.

Adults: IV infusion over 30 mins. 100 mg every 3 mos; some patients may benefit from 300 mg every 3 mos.

Children: Not established.

Adults: 70 mg SC once monthly; some patients may benefit from 140 mg monthly. Children: Not established.

Adults: 225 mg SC once monthly or 675 mg (three 225 mg injections) every 3 mos. Children: Not established.

Adults: Initially 240 mg SC loading dose (two 120 mg injections), followed by 120 mg monthly.

Children: Not established.

Rimegepant Nurtec ODT Adults: Episodic migraine: 75 mg ODT every other day. The safety of using more than 18 doses in a 30-day period has not been established. Children: Not established.

Notes

IM, intramuscular; IV, intravenous; ODT, orally disintegrating tablets; SC, subcutaneous injection; soln, solution; supp, suppositories aTable is not an inclusive list of medications, official indications, and/or dosages. Please see drug monographs at eMPR.com, contact companies for full drug labeling and/or consult your health care provider. Reprinted with permission from eMPR.com.

practice. According to Haines and Jones’s Translation Model, these long delays result in suboptimal patient care outcomes. To build an overall culture change, multiple dissemination approaches to aid PCPs with complex migraine preventive management should be utilized.19

Preventive migraine therapies include pharmacologic (Table 2) and biobehavioral therapies, as well as neuromodulation devices for migraine patients with 6 or more migraine headache days per month.The AHS launched the First Contact — Headache in Primary Care website16 to provide access to current information from headache specialists and to provide educational resources for PCPs.

Case Resolution

The patient was diagnosed with episodic menstrually-related migraines. She was prescribed frovatriptan 2.5 mg to be started 2 days prior to the onset of menses for menstrual migraine prophylaxis (2.5 mg twice daily for 6 days). She was also prescribed rimegepant as needed for acute headache (75 mg for a total of 8 doses a month). Rimegepant is an orally disintegrating tablet that has a fast onset of action. She wanted a fast-acting medication that did not need to be taken with water because it is difficult for her to leave the classroom when her headache starts. She is very pleased with her treatment outcome: since starting frovatriptan, she has experienced only 1 or 2 moderate headaches a month, for which she takes rimegepant, which works within 15 to 20 minutes.

Conclusion

When possible, migraine should be managed by a primary care provider. However, many primary care providers do not utilize the full spectrum of migraine preventive management options and prescribe preventive medications mostly for patients with chronic migraines.The lack of familiarity with the current AHS recommendations could be the single most important factor contributing to the failure to treat migraines preventively. Adherence to the latest AHS migraine preventive management recommendations helps to improve inadequate preventive treatment, minimize barbiturate and opioid overuse, and decrease the average 4-year gap between diagnosis and initiation of preventive medications. Providers can also download the free Android or Apple app Primary Care Migraine© developed by The National Headache Foundation (www.pcmigraine.com). ■

Vera Gibb, DNP,APRN, FNP-C,AQH, CCTP, is an assistant professor in the Graduate Studies Department of The University of Texas Medical Branch at Galveston School of Nursing, Galveston,Texas. She practices at Village Medical, Friendswood,Texas. Safa’a Al-Arabi, PhD, RN, MPH, MSN, is an associate professor and the Clinical Nurse Leader (CNL) Track Administrator in the Graduate Studies Department of The University of Texas Medical Branch at Galveston School of Nursing.

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