It’s a promising time for people with migraine, as recent treatments — both preventive and acute — are already changing lives for the better.
Among the more exciting advances in migraine research are gepants, a therapeutic approach unlike other migraine treatments. Gepants block calcitonin gene-related peptides (CGRPs), proteins that regulate the size of blood vessels in our brains. CGRPs are linked to the frequency and severity of migraine. Building up in and around the nervous system, they activate pathways that lead to head pain.
Recent studies show that CGRP levels within the blood increase during migraines. And in people who experience chronic migraine (at least 15 attacks per month), CGRP levels may tend to be consistently higher, even when they’re not having a migraine.
Gepants act as CGRP antagonists or inhibitors, aimed at reducing those CGRP levels. Like triptans developed in the 1990s, gepants were developed specifically for treatment of migraine. Other medications used to treat migraine — medications not originally developed for that purpose (for example, antidepressants, anti-epilepsy drugs, and botox) — may cause side effects for some people with migraine.
Gepants are currently available in the U.S. for acute and preventive treatment of both episodic and chronic migraine headaches. You may recognize the following brand names:
Let’s answer a few questions about gepants and how they function:
Gepants are the first line of treatment developed specifically for migraine since triptans first emerged in the 1990s. Gepants regulate CGRP levels in the blood and brain by blocking either the protein receptors or the protein itself.
This blocking action prevents the spikes in CGRP levels associated with migraine. The result: reduced frequency of attacks, shorter duration, and potentially less pain and other symptoms.
Prior CGRP antagonist treatments called for three injections of CGRP-targeted monoclonal antibodies. Intended only as a preventative, these injections required a trip to a clinic once a month, or every 3 months, depending on the type of antibody used.
Gepants, on the other hand, are small molecules that work more speedily than monoclonal antibodies to relieve migraine symptoms. As a preventative, the medication is taken around the same time each day, in pill form or as dissolvable tablets. For episodic migraine, individuals can heed the early warning signs of migraine that occur with prodrome, prompting them to take their gepants medication for quick, effective relief.
While gepants are now available to prevent as well as halt migraines, anti-CGRP monoclonal antibodies (CGRP mAbs) are approved for migraine prevention only, and are prescribed mainly for people with chronic or near-chronic migraines. Self-injected or administered intravenously, they are well tolerated and tend to show little or no interaction with other types of medications as they do not enter the stomach.
CGRP mAbs take longer to work than gepants, although they do work more quickly than tension, depression, or seizure medications often prescribed to help treat migraines. According to Virtual Headache Specialist, if an individual doesn’t respond well to a particular CGRP mAb, it may be worth trying another as the alternative option may well produce a better outcome.
CGRP mAbs currently available include:
Overall, studies of anti-CGRP treatments found them effective at reducing attack frequency and relieving symptoms, often with fewer side effects than existing medications. CGRP inhibitors are FDA-approved to treat both episodic and chronic migraine, and can be used as an acute migraine treatment or as a preventive strategy. They are also proven effective for migraine with and without aura.
Gepants were formulated with a goal of suiting all individuals who get migraines. A 2019 study showed that the newest gepants treat migraine headaches as well as triptans or ditans, but with greater tolerability and less likelihood of adverse effects, making them potentially appropriate for a wider range of patients.
CGRP inhibitors are FDA-approved to treat both episodic and chronic migraine, and can be used as an acute migraine treatment or as a preventive strategy. They are also proven effective for migraine with and without aura.
Most research suggests that the risk of medication overuse headache (MOH) – a frequent issue with oral medication for acute migraine – is not present with gepants. This means they can be taken as often as needed, unlike the oral medications.
A study of over 46,000 migraine patients across 64 clinical trials compared triptans, ditans and gepants. Gepants had the lowest risk of adverse effects, followed by triptans, then ditans (which had the highest risk of adverse effects amongst all treatments).
The most common side effects of gepants reported in clinical trials were nausea and fatigue.
CGRP inhibitors offer an alternative migraine treatment option when other migraine medications have failed to give you relief, or if you’ve experienced side effects from them. Because gepants are still a relatively new treatment path for migraine, with long-term effects not yet known, a healthcare professional is likely to prescribe them to individuals who’ve tried a number of treatments with no lasting, positive outcome.
Scientists are still debating whether gepants are safe for use during pregnancy, so it’s best to avoid them if you are pregnant or planning to be. People with serious conditions — such as heart disease or diabetes — should consult a healthcare professional before taking gepants to be sure they won’t conflict with other medical treatments.
Before you commit to anti-CGRP therapy or other forms of migraine treatment, a smart approach can be to investigate which migraine medications are most likely to work for you, based on your unique genetic profile. Mable's DNA test can help determine if anti-CGRP therapy or another treatment is an optimal match for your specific symptoms and needs.
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