Neurologist Dr. Susan Lee answers common questions about new treatments for migraine and where the future of migraine research is headed.

Standard treatments taken at the onset of a migraine episode (also called acute or abortive treatment) include oral medications, such as:

The Ask the Expert logo which features the words "Ask" and "Expert" in black bold letter and the word "the" in a teal speech bubble
  • over-the-counter analgesics (pain relievers), such as aspirin, ibuprofen (Advil, Motrin IB), and acetaminophen (Tylenol)
  • triptans, such as sumatriptan (Imitrex) and rizatriptan (Maxalt)
  • ergots, such as dihydroergotamine (DHE-45, Migranal)
  • anti-nausea medications, such as metoclopramide (Reglan, Metozolv ODT) and ondansetron (Zofran, Zofran ODT, Zuplenz)

Traditionally, oral migraine preventive medications were those that served dual purposes, including:

  • anti-hypertensives, such as propranolol (Hemangeol, Inderal, InnoPran XL) and verapamil (Calan, Calan SR, Verelan)
  • antiseizure drugs, such as topiramate (Topamax, Eprontia) and valproate (Depakene, Depakote, Stavzor)
  • antidepressants, such as amitriptyline (Elavil, Vanatrip) and venlafaxine (Effexor, Venbysi XR)

Botox injections were Food and Drug Administration (FDA)-approved for chronic migraine in 2010.

This is a very exciting time for migraine treatment due to the introduction of migraine-specific treatments. These treatments target specific pathways and mechanisms thought to be involved in migraine.

Within the past few years, several newer treatments have been introduced. These include:

  • calcitonin gene-related peptide (CGRP) antagonists
  • lasmiditan
  • neuromodulating devices

The first CGRP antagonist, erenumab (Aimovig), heralded a new wave of migraine medications as CGRP antagonists were the first migraine-specific medications to be approved since triptan therapy was introduced in the early 1990s.

CGRP antagonists include:

  • injectable medications for preventive treatment, such as erenumab, galcanezumab-gnlm (Emgality), fremanezumab (Ajovy), and eptinezumab-jjmr (Vyepti)
  • oral medications for acute treatment, such as ubrogepant (Ubrelvy) and rimegepant (Nurtec)
  • oral medication for migraine prevention, such as rimegepant and atogepant (Qulipta).

The CGRP antagonists are also unique in that they offer varying modes of delivery (as discussed below).

Lasmiditan (Reyvow) is a serotonin 5-HT1F receptor agonist indicated for the acute treatment of migraine.

The neuromodulating devices each target different nerves thought to mediate migraine pain. These devices can be used to treat a migraine episode in the moment or as daily preventive therapy. They include:

  • GammaCore
  • Cefaly
  • Nerivio
  • Relivion
  • sTMS mini (single-pulse transcranial magnetic stimulation)

The newer preventive treatments are the injectable CGRP antagonists (erenumab, galcanezumab-gnlm, fremanezumab-vfrm, and eptinezumab-jjmr) and the oral drug atogepant (Qulipta), also known as a gepant.

These have been shown to have a favorable side effect profile, including a favorable cardiovascular safety profile.

There are no definitive studies comparing the efficacy of the newer treatments to the previously available preventive treatments for migraine.

However, eptinezumab-jjmr has been shown to be effective for migraine prevention from day 1 of administration and to maintain its level of efficacy throughout 12 to 18 months of treatment.

The newest short-term migraine treatments are the CGRP antagonists ubrogepant, rimegepant (which has a dual indication for both acute and preventive migraine treatment), and zavegepant (Zavzpret).

As discussed above, these medications have a favorable side effect profile and have not been shown to increase cardiovascular or bleeding risk, which may occur with some of the older treatments (such as triptans or nonsteroidal anti-inflammatory drugs).

Lasmiditan (Reyvow), while proven effective for acute treatment of migraine and considered safe in patients with cardiovascular disease, is known to cause dizziness and driving impairment.

Therefore, patients given this medication should not drive or operate potentially hazardous machinery for at least 8 hours after taking this medication.

CGRP stands for calcitonin gene-related peptide. It’s a neuropeptide (brain chemical) that’s released from nerves and arteries and found to be elevated during migraine attacks, thus mediating pain during a migraine episode.

The discovery of CGRP’s role in migraine has revolutionized migraine treatment. CGRP antagonists act to block CGRP, thereby decreasing migraine symptoms or preventing them altogether.

Current research in this field has focused on different CGRP-targeted therapies, such as:

  • monoclonal antibodies, including:
    • erenumab
    • galcanezumab-gnlm
    • fremanezumab
    • eptinezumab-jjmr
  • small, gepant molecules, including:
    • ubrogepant
    • rimegepant
    • atogepant
    • zavegepant

The latest migraine treatments include:

  • at-home injections, such as erenumab, galcanezumab-gnlm, fremanezumab (Ajovy)
  • orally disintegrating tablets (rimegepant)
  • IV infusions (eptinezumab-jjmr)
  • intranasal sprays (zavegepant)

There are also neuromodulating devices that may be:

  • worn on or around the head (Cefaly, Relivion)
  • worn around the arm (Nerivio)
  • placed at the back of the head (sTMS)
  • used as a stimulator to the neck (Gammacore)

A transdermal patch device (Zecuity) was previously available, but this treatment was withdrawn due to safety concerns.

The different delivery systems for migraine treatment allow prescribers and patients to choose the best mode of delivery based on the type of migraine and patient characteristics.

The identification of migraine biomarkers would allow for a more accurate diagnosis of migraine. Currently, migraine is a clinical diagnosis.

Reliable and accurate diagnosis of the condition using biomarkers would allow for earlier treatment. Additionally, identifying migraine biomarkers could potentially allow for personalized migraine treatment by targeting specific biomarkers.

Future migraine treatments are likely to focus on varying migraine biomarkers.

Much of the research on lifestyle changes for migraine focuses on sleep, stress reduction, and nutraceuticals (foods that may offer health benefits beyond their nutritional value).

There are now several wearable devices to help track and improve sleep.

Smartphone technology, including apps, is also available to help migraine patients track their migraine episodes. Apps also provide resources for stress management, such as meditation and cognitive behavioral therapy (CBT), to help manage migraine symptoms.

Finally, there’s increased interest in nutraceuticals as a “natural” treatment of migraine, with increasing data to support its use.

I believe personalized medication will continue to grow, including in the field of migraine. The ideal migraine treatment would be one tailored to meet each individual’s specific set of symptoms, taking into account their genetics and comorbidities. It would be exciting to see migraine research head in this direction.

Furthermore, a relatively unknown and uncommon treatment for migraine is surgical intervention, either through nerve decompression surgery or the implantation of a stimulating device.

Additional research is warranted to determine if these surgical treatments are safe and effective. While we do not yet have a cure for migraine, there are more treatment options than ever and more on the horizon.

Dr. Susan W. Lee is an ABMS board certified neurologist with fellowship training in clinical neurophysiology. She currently practices in Los Angeles, California, and her subspecialty interests include the management of epilepsy and headache disorders.