Migraine Care: Prevention, Treatment, and Medication Management

Twelve percent of the US population experiences migraine, according to the Migraine Research Foundation. Migraine is the third most prevalent illness globally, and it affects 1 out of 4 US households. Moreover, migraine can be disabling, with 90% of those affected worldwide unable to work or function normally during a migraine attack.¹

Migraine Phases and Symptoms

Although migraine is sometimes thought of as just a headache, a migraine attack can involve 4 phases of various symptoms. Not every stage is present in every migraine. Pharmacists can counsel patients to keep track of their migraines with a headache journal or app because neurologists and headache specialists may be able to pinpoint patterns and detect a migraine attack before it arrives.²

A migraine attack can manifest with any of the 4 phases:

• Prodrome: This is a “preheadache” and can last several hours to several days. Symptoms include mood changes (eg, depression, irritability), sensitivity to light and sound, insomnia or fatigue, and stomach problems (eg, nausea, vomiting, diarrhea). Unique symptoms include yawning, food cravings, and increased urination.
• Aura: This phase can last from 5 to 60 minutes. Symptoms include vision disturbances, such as blurry vision or vision loss, and/or seeing patterns or flashing or shimmering lights.
• Headache: This phase can last from 4 to 72 hours. The hallmark symptom is pain, often on one side or one part of the head. Other symptoms like nausea, vomiting, anxiety, and sensitivity to light and sound may occur.
• Postdrome: This “hangover” phase usually lasts 24 to 48 hours. Symptoms may include fatigue, body pain, dizziness, and mood changes.²

One way to remember migraine symptoms is with the acronym POUND³:

P: pulsating pain

O: 1-day duration of severe untreated attacks

U: unilateral pain 

N: nausea and vomiting

D: disabling intensity

When to Consult a Specialist

It is prudent to refer patients who have frequent headaches, headaches that are increasing in severity or frequency, or headaches that interfere with functioning to a headache specialist for evaluation and a treatment plan, including preventive and acute treatment.⁴

If the patient experiences a new or unusual symptom, such as a headache that occurs within a few seconds or the worst headache they’ve ever had, refer the patient to the emergency department. Other symptoms that require emergency treatment include pain for more than 72 hours, fever, weakness, vision loss or changes, and confusion or if the patient is pregnant, is immunocompromised, or has a severe medical condition like liver or kidney disease.^4,5

Migraine Prevention

Nonpharmacological prevention of migraine

Some nonpharmacological migraine prevention tips for patients include^6,7:

• Tracking: Keep detailed information in a headache diary or app.
• Trigger avoidance: Avoid known triggers such as odors, smoke, alcohol, stress, and food triggers.
• Sleep: Keep a regular sleep schedule by waking up and going to bed at the same times every day, including weekends.
• Diet: Eat regular, healthy meals and limit sugar. Drink plenty of water to avoid dehydration. Limit alcohol and caffeine. Avoid food triggers such as aged cheeses, chocolate, MSG, and cured meats.
• Exercise: Try to get moderate, regular exercise 3 to 5 times weekly.
• Reduce stress: Lower stress with relaxation, yoga, or stress management.

Pharmacological prevention of migraine

Patients who have 4 or more migraine attacks, 8 or more migraine days per month, or other qualifying factors may need preventive treatment.⁷ Many options are available, and some of the more common preventive treatment medications include the following⁷:

β-Blockers (propranolol or metoprolol)

• Counsel patients on adverse effects (AEs) such as fatigue, depression, sexual problems, decreased heart rate, and low blood pressure.

Anticonvulsants (divalproex or topiramate)

• Divalproex: Counsel on nausea, vomiting, fatigue, and lab monitoring due to possibility of liver or pancreas problems.
• Topiramate: Counsel on paresthesia, stomach pain, fatigue, memory problems, kidney stones, nausea, vomiting, altered taste, weight loss, eye pain, and lab monitoring due to possibility of liver problems and metabolic acidosis.

Antidepressants (such as amitriptyline or venlafaxine)

• Counsel patients on the risk of suicidal thoughts and behavior and the importance of tapering when discontinuing medication.
• Amitriptyline: Counsel on anticholinergic AEs such as dry mouth, blurry vision, constipation, urinary retention, and weight gain.

CGRP inhibitors

Calcitonin gene-related peptide (CGRP) inhibitors are a newer class of drugs that prevent migraine by targeting CGRP, which is found in higher levels during a migraine attack. CGRP inhibitors are monoclonal antibodies that block the effects of CGRP and are the first class of medications specifically designed to prevent migraine.

CGRP inhibitors approved by the FDA for the prevention of migraine are as follows^8-12:

• Erenumab-aooe (Aimovig; Amgen): 70 to 140 mg injected subcutaneously once monthly
• Fremanezumab-vfrm (Ajovy; Teva Pharmaceutical Industries Ltd): 225 mg injected subcutaneously once monthly or 675 mg injected every 3 months (as 3 consecutive injections of 225 mg each)
• Galcanezumab-gnlm (Emgality; Eli Lilly and Company): 240 mg (2 consecutive doses of 120 mg) injected subcutaneously as a loading dose, then 120 mg once monthly
• Eptinezumab-jjmr (Vyepti; Lundbeck Seattle BioPharmaceuticals, Inc): 100 mg or 300 mg by intravenous infusion every 3 months

Common AEs associated with CGRP inhibitors include injection-site reactions (pain, redness, itching) and hypersensitivity reactions.^9-12 Other AEs of erenumab-aooe include constipation (possibly with complications including hospitalization) and increased blood pressure.⁹ Eptinezumab-jjmr may also cause nasopharyngitis.¹³

Migraine Treatment

Many options are available for migraine treatment. Product selection may be based on a variety of factors, including symptoms, medical history, other medications, patient preference for specific formulation(s), AEs, and cost or insurance considerations (TABLE).¹⁴

Pharmacists can provide counseling on the following popular first-line medications for migraine treatment.

OTC options

For mild to moderate migraine attacks, acetaminophen and oral nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen, or naproxen may be used. Although acetaminophen is less effective than NSAIDs for migraine, it has fewer AEs. The combination in acetaminophen/aspirin/caffeine (Excedrin; Novartis) is also a first-line option.¹⁴

Counseling can include dosage, limitations, and the importance of avoiding alcohol. For NSAIDs and acetaminophen/aspirin/caffeine, also counsel patients on the risk of potential gastrointestinal and cardiovascular effects.¹⁵

Triptans

Triptans are effective as a first-line treatment for moderate to severe migraine. Triptans approved by the FDA for the treatment of migraine include the following14:

• Naratriptan (Amerge; GlaxoSmithKline)
• Almotriptan (Axert; Teva Pharmaceutical Industries Ltd)
• Frovatriptan (Frova; Vernalis)
• Sumatriptan (Imitrex; GlaxoSmithKline)
• Rizatriptan (Maxalt; Merck)
• Eletriptan HBr (Relpax; Pfizer Inc)
• Zolmitriptan (Zomig; AstraZeneca)

Triptans have slight differences that may cause patients to respond to certain triptans but not others. Triptans are most effective when taken early in a migraine attack and are generally well tolerated. Most triptans, with the exception of almotriptan and frovatriptan, can cause fatigue, dizziness, chest pain, and nausea.¹⁴

Other new drugs have entered the market for migraine prevention and/or treatment.

• Rimegepant (Nurtec ODT; Biohaven) is an orally disintegrating tablet indicated for both the treatment and prevention of migraine. The main AEs are nausea and abdominal pain.
  
• Ubrogepant (Ubrelvy; Allergan) is indicated for acute treatment of migraine. The most common AEs are nausea and somnolence.
• 
  Lasmiditan (Reyvow; Eli Lilly and Company) is indicated for acute treatment of migraine. The most common AEs are dizziness, fatigue, paresthesia, and sedation.

Medication-Overuse Headache

An important consideration when talking with patients is the possibility of medication-overuse headache, also known as a rebound headache—part of a vicious cycle of having headaches and taking more and more medication to relieve them, which results in near-daily or daily headaches.¹⁶

Patients who experience headaches every day, or almost every day, especially when the pain begins upon awakening, may be experiencing a medication-overuse headache. Refer the patient to a headache specialist, who can help the patient establish a new treatment plan that includes stopping acute medications, starting preventive treatment, and slowly reintroducing a limited amount of acute medicines as needed.¹⁶

Drug Interactions and Serotonin Syndrome

An essential consideration in either preventive or acute treatment is the presence of drug interactions. Pharmacists can help patients by checking for drug interactions and being especially aware of the possibility of serotonin syndrome, a life-threatening condition that is more likely to occur with triptans and other medications that increase serotonin levels.

References

1. Migraine facts. Migraine Research Foundation. Accessed April 12, 2021. https://migraineresearchfoundation.org/about-migraine/migraine-facts/
2. The timeline of a migraine attack. American Migraine Foundation. January 18, 2018. Accessed April 12, 2021. https://americanmigrainefoundation.org/resource-library/timeline-migraine-attack/.
3. When headaches are more than a pain. Harvard Health Publishing. March 2019. Accessed April 15, 2021. https://www.health.harvard.edu/pain/when-headaches-are-more-than-a-pain
4. Know your headaches. Cedars-Sinai blog. February 8, 2018. Accessed April 12, 2021. https://www.cedars-sinai.org/blog/know-your-headaches.html
5. When to go to the emergency room for a headache or migraine. American Migraine Foundation. February 13, 2017. Accessed April 12, 2021. https://americanmigrainefoundation.org/resource-library/when-to-go-to-the-er-for-headache-migraine/
6. Trigger avoidance information. American Headache Society. Accessed April 12, 2021. https://americanheadachesociety.org/trigger-avoidance-information/
7. Ha H, Gonzalez A. Migraine headache prophylaxis. Am Fam Physician. 2019;99(1):17-24. Accessed April 27, 2021. https://www.aafp.org/afp/2019/0101/p17.html
8. Mohanty D, Lippmann S. CGRP inhibitors for migraine. Innov Clin Neurosci. 2020;17(4-6):39-40. Accessed April 27, 2021. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413335/
9. New drug class employs novel mechanism for migraine treatment and prevention. FDA. Updated January 29, 2019. Accessed April 14, 2021.https://www.fda.gov/drugs/news-events-human-drugs/new-drug-class-employs-novel-mechanism-migraine-treatment-and-prevention
10. Aimovig- erenumab-aooe injection. DailyMed. Updated February 11, 2021. Accessed April 14, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b998ed05-94b0-47fd-b28f-cddd1e128fd8
11. Ajovy- fremanezumab-vfrm injection. DailyMed. Updated October 27, 2020. Accessed April 14, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e344ea-5916-4947-b6f2-4a76ccc04b6b
12. Emgality- galcanezumab-gnlm injection, solution. DailyMed. Updated September 28, 2020. Accessed April 14, 2021.https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=33a147be-233a-40e8-a55e-e40936e28db0
13. Vyepti- eptinezumab-jjmr injection. DailyMed. Updated February 21, 2020. Accessed April 14, 2021. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79065861-6aa5-4d1f-829f-3a6471286b36
14. Mayans L, Walling A. Acute migraine headache: treatment strategies. Am Fam Physician. 2018;97(4):243-251. Accessed April 27, 2021. https://www.aafp.org/afp/2018/0215/p243.html
15. Ghlichloo I, Gerriets V. Nonsteroidal anti-inflammatory drugs (NSAIDs). In: StatPearls (Internet).StatPearls Publishing; 2021. Accessed April 14, 2021. https://www.ncbi.nlm.nih.gov/books/NBK547742/
16. Medication overuse headaches. Cleveland Clinic. Updated December 18, 2020. Accessed April 14, 2021.https://my.clevelandclinic.org/health/diseases/6170-medication-overuse-headaches