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Migraine

Migraine Overview

Migraine is a primary headache disorder that is often characterized by a throbbing and pulsating pain accompanied by other symptoms, like sensitivity to light, sound, and nausea. It is not necessary for all of those associated symptoms to be present, though some combination of them is necessary to make the diagnosis.

The pathophysiology of migraine is very complex and is thought to be caused by a combination of predisposing factors, like genetics, a person’s sex and hormones, and environment. Patients with migraine have genetic differences in the excitability of the sensory nerves of the head, neck and brain compared to those without migraine. This can lead to abnormal coordination of signaling between certain parts of the brain, which ultimately leads to the development of pain and other migraine-associated symptoms.

The trigeminal nerve and its branches are the most responsible for relaying the pain signals during a migraine attack. The different branches of this nerve supply sensory information from the lining of the brain, several arteries and veins around the brain. Other nerves, particularly branches of the C1, C2, and C3 levels, which form the occipital nerves, are also likely involved in causing migraine pain.

Migraine Symptoms

Untreated migraine attacks can last for hours, days, or months. For some people, migraines may progress through four stages:

  1. Prodrome/premonitory
  2. Aura
  3. Headache
  4. Postdrome

Not all patients with migraine experience all four phases listed above. For example, only about 30-40% of migraine patients will experience two auras during their life, which is the number necessary to be diagnosed with “migraine with aura.”

Prodrome, or the premonitory phase, may occur one or two days before you have a migraine attack. You may notice the following symptoms:

  • Food cravings
  • Unexplained mood changes, such as depression or euphoria
  • Uncontrollable yawning
  • Increased thirst and urination
  • Neck stiffness

If experienced, an aura typically occurs prior to the onset of migraine pain. The duration of an aura can be variable, but it is expected to last somewhere between five and 60 minutes. Migraine pain often follows the resolution of the aura. It is more common to have migraine headaches without aura. Aura symptoms may include:

  • Visual disturbances
  • Numbness/tingling
  • Weakness
  • Speech difficulties
  • Confusion
  • Dizziness
  • Difficulty walking

It is very important to recognize that migraine aura can mimic symptoms of a stroke, which is a serious, life-threatening condition. It can take an experienced and knowledgeable physician to confidently differentiate between the two conditions, so if you are experiencing or have experienced the sudden onset of any of the above symptoms, we recommend you notify your physician immediately or call 911.

During the headache phase (also called a migraine attack), you may have the following symptoms:

  • Pulsating, throbbing pain that is usually on one side of the head or worse on one side compared to the other and that starts gradually builds over minutes to hours
  • Sensitivity to light, sounds, smell, or touch
  • Nausea, with or without vomiting
  • Blurred vision
  • Avoidance of activity or exertion

In the postdrome phase that follows a migraine headache, you may experience the following for up to 24 hours:

  • Exhaustion
  • Moodiness or euphoria
  • Dizziness
  • Weakness
  • Confusion
  • Sensitivity to light and sound

Many medical conditions can cause headaches and other symptoms. Contact a medical professional if you are experiencing symptoms.

Migraine Treatments

Rescue Treatments

Rescue treatments describe medicines that are given when a migraine is beginning, or when a migraine has already started. The goal of rescue treatment is to stop migraine pain from continuing. Regardless of the treatment that is chosen, it should be used at the onset of the headache. The longer you wait to treat a headache, the less likely it is to respond to medication.

Over-the-counter medications

There are several over-the-counter medication options available for the treatment of migraine. It is very common for patients to try one or several of these options before they ever see a physician for their headache disorder. Commonly used over-the-counter medications used for migraine are NSAIDs (non-steroidal anti-inflammatory drugs) and Tylenol. Several combination medications exist that contain NSAIDs with caffeine, like Excedrin.

It is not uncommon for over-the-counter medications to be ineffective for migraine, and patients will sometimes use these medications more frequently than recommended. There are several possible side effects to over-the-counter medications that are important to be mindful of. Some of these side effects are serious and potentially life-threatening. Another possible risk of overusing medication is the development of medication-overuse headache. This condition can occur in patients with an existing headache disorder and typically causes the original headache disorder to worsen. Try to avoid using over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen more than 15 days per month. Preventative medication should be used if headaches occur frequently.

Triptans and DHE

Triptans are a class of medications commonly used to provide fast relief for migraine headaches. They work by activating the receptors for the neurotransmitter serotonin in the brain, reducing blood vessel dilation and release of the neurotransmitters that cause pain and other symptoms of migraine. Triptan medications are available as oral tablets, orally dissolving tablets, nasal sprays, and subcutaneous injection. There are seven different triptans available on the market.

Another option is dihydroergotamine (DHE), which binds to serotonin and dopamine receptors on nerve cells and decreases the transmission of pain messages along nerve fibers. Ergot derivative drugs may also be given as an injection (intramuscular or IV) or a nasal spray.

Small Molecule CGRP Antagonists (gepants)

Medications that work by blocking the activity of calcitonin gene-related peptide (CGRP) have been approved for the acute treatment of migraine pain. CGRP is a protein that is elevated during a migraine attack and can cause dilation of blood vessels and migraine pain.

The two medications in this class available for acute migraine treatment are called ubrogepant (Ubrelvy) and rimegepant (Nurtec).

Ubrelvy is available in two doses, 50mg and 100mg oral tablets. The dose can be repeated after two hours if the initial dose was ineffective. It is generally well tolerated but it could cause nausea, sleepiness, or dry mouth.

Nurtec is available in one dose, a 75mg oral disintegrating tablet. Patients are limited to one dose per 24-hour period. Like Ubrelvy, Nurtec tends to be well-tolerated, but could cause nausea.

Ditans

Another acute migraine medication is called lasmiditan (Reyvow). Like triptans and DHE, it works by activating serotonin receptors in the brain.

Unlike triptans or DHE, Reyvow does not cause constriction of blood vessels. For this reason, it is considered to be safe for patients who have coronary artery disease, hypertension, history of stroke, and history of heart attack. 

Preventative Treatments

The goal of preventative treatments for migraines is to stop the pain from happening in the first place, or to reduce the number and severity of migraine headaches.

Lifestyle Changes

The following lifestyle changes may help prevent migraine attacks:

  • Maintaining good sleep habits
  • Eating a healthy diet with regularly scheduled meals
  • Staying hydrated
  • Avoiding suspected triggers
  • Regular exercise

Headache Diary

Documenting the following in a “headache diary” can help you identify your triggers:

  • Day and time the pain began
  • What you ate and drank in the previous 24 hours
  • How much you slept
  • Stress or other emotions you were experiencing before the pain began
  • What you were doing when the pain began

The following medications may also help prevent migraine attacks:

Botox for Migraine Prevention

Botox is a drug that is often used to temporarily smooth facial wrinkles, but it can also be an effective treatment for chronic migraine. It is thought to work by preventing the release of the neurotransmitters that cause migraine. The treatment consists of 31 injections in the head and neck every 12 weeks. Each treatment takes about five to 10 minutes, and the injections have been described as feeling like tiny pinpricks.

Nerve blocks

Nerve blocks involve injecting a local anesthetic (e.g., bupivacaine or lidocaine) into the area of certain nerves associated with headache pain.

  • Occipital nerve block focuses on the area around the occipital nerves, which are located in the back of the head.
  • Trigeminal nerve block focuses on the area around the trigeminal nerve, which carries sensation from the face to the brain.
  • Sphenopalatine ganglion block focuses on the sphenopalatine ganglion, a group of trigeminal nerve cells located behind the nose. This procedure differs from occipital and trigeminal nerve blocks because it does not involve a needle. Instead, a flexible catheter is advanced up the nostril toward the SPG and lidocaine is slowly dripped onto the nerve endings.

Other Medications

  • Blood pressure medications may help reduce the frequency and severity of migraines. These include:
    • Beta blockers (e.g., propranolol (Inderal), metoprolol tartrate (Lopressor, Toprol))
    • Calcium channel blockers (e.g., verapamil (Verelan, Calan, Covera, Isoptin), diltiazem (Cardizem, Dilt-cd, Tiazac, Dilacor))
  • Antidepressants may be effective in preventing migraines, even in people without depression. These include:
    • Tricyclic antidepressants, or TCAs (e.g., amitriptyline (Elavil) and nortriptyline (Pamelor))
    • Selective serotonin reuptake inhibitors,  or SSRIs (e.g., fluoxetine (Prozac), paroxetine (Paxil, Pexeva, Brisdelle))
    • Serotonin-norepinephrine reuptake inhibitor, or SNRIs (e.g., venlafaxine (Effexor))
  • Antiseizure medications may reduce the frequency of migraines. These include:
    • Topiramate (Topamax)
    • Valproate (Depakote)
  • CGRP monoclonal antibodiesare medications that are administered either as once-monthly injections at home or by IV infusion once every three months. These include:
    • Erenumab (Aimovig)
    • Fremanezumab (Ajovy)
    • Galcanezumab (Emgality)
    • Eptinezumab (Vyepti)
  • Small molecule CGRP antagonists are medications that work by blocking the activity of calcitonin gene-related peptide (CGRP). Nurtec and Ubrelvy were listed above as acute or rescue medications for migraine, but there exist two small molecule CGRP antagonists for the prevention of migraine: rimegepant (Nurtec) and atogepant (Qulipta). Nurtec has approval from the FDA for both rescue and preventative indications, but the dosing frequency is different depending on the way you take the medication. Qulipta is an oral tablet that has three different dosing options available.

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Additional Information

How common are migraines?

About 12 percent of the United States population experiences migraines.

Who gets migraines?

Migraines are three times more common in women than in men, and attacks usually begin sometime between childhood and early adulthood.

Migraine sufferers typically have other family members with migraines. Although migraines seem to be genetic, few specific genes have been identified.

Migraines occur more frequently in people with other medical conditions, such as depression, anxiety, bipolar disorder, sleep disorders, and epilepsy.

Migraine triggers vary from person to person, but common triggers include:

  • Sudden weather changes
  • Too much or too little sleep
  • Strong odors or fumes
  • Stress or other emotions
  • Overexertion
  • Sudden or loud noises
  • Illness
  • Skipping meals
  • Tobacco use
  • Head and neck trauma
  • Certain medications, as well as medication overuse or missed preventive medication doses
  • Hormonal changes and menstrual cycle
  • Bright or flashing lights
  • Certain foods, food additives, and drinks, such as processed meats, cheese, dark chocolate, aspartame, MSG, and red wine

How are migraines diagnosed?

Your doctor may use the following to diagnose migraines:

  • Personal and family medical history
  • Physical and neurological examinations
  • Imaging tests to rule out other headache causes if necessary

Additional Resources

National Institute of Neurological Disorders and Stroke
American Migraine Foundation

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About 12 percent of the United States population experiences migraines.

References

  1. Cowan RP, Rapoport AM, Blythe J, Rothrock J, Knievel K, Peretz AM, Ekpo E, Sanjanwala BM, Woldeamanuel YW. Diagnostic accuracy of an artificial intelligence online engine in migraine: A multi-center study. Headache. 2022 Jul;62(7):870-882. doi: 10.1111/head.14324. Epub 2022 Jun 3. PMID: 35657603; PMCID: PMC9378575.
  2. Blumenfeld AM, Knievel K, Manack Adams A, Severt L, Butler M, Lai H, Dodick DW. Ubrogepant Is Safe and Efficacious in Participants Taking Concomitant Preventive Medication for Migraine: A Pooled Analysis of Phase 3 Trials. Adv Ther. 2022 Jan;39(1):692-705. doi: 10.1007/s12325-021-01923-3. Epub 2021 Dec 7. PMID: 34874514; PMCID: PMC8799553.
  3. Knievel K, Buchanan AS, Lombard L, Baygani S, Raskin J, Krege JH, Loo LS, Komori M, Tobin J. Lasmiditan for the acute treatment of migraine: Subgroup analyses by prior response to triptans. Cephalalgia. 2020 Jan;40(1):19-27. doi: 10.1177/0333102419889350. Epub 2019 Nov 19. PMID: 31744319; PMCID: PMC6950889.
  4. Blumenfeld AM, Kaur G, Mahajan A, Shukla H, Sommer K, Tung A, Knievel KL. Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review. Pain Ther. 2023 Feb;12(1):251-274. doi: 10.1007/s40122-022-00452-3. Epub 2022 Nov 22. PMID: 36417165; PMCID: PMC9845441.
  5. Ailani J, Lipton RB, Hutchinson S, Knievel K, Lu K, Butler M, Yu SY, Finnegan M, Severt L, Trugman JM. Long-Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52-Week Extension Trial. Headache. 2020 Jan;60(1):141-152. doi: 10.1111/head.13682. Erratum in: Headache. 2021 Jun;61(6):978-981. PMID: 31913519; PMCID: PMC7004213.
Medically Reviewed by Kerry Knievel, DO, FAHS and Shane Root, MD on September 4, 2022