Over the past decade, there has been a significant amount of progress made in the development of new preventative migraine therapies that differ from previous treatment types. One such breakthrough was the recent FDA approval of medications in a novel class of drugs known as calcitonin gene-related peptide (CGRP) antagonists, which reduce the burden of migraine with minimal side effects. Subsequently, they are considered favorable alternatives to older migraine drugs which can have more side effects for certain populations. In addition to the anti-CGRP class of migraine medications that are now on the market, there are new treatments that are currently in development for the prevention of migraine headaches.
One of the more recent advances in migraine treatment has been the use of oral anti-CGRP medicines for migraine prevention which are presently under research. It is felt that one of the ways that anti-CGRP medicines are effective at preventing migraine attacks may be due to inhibiting the inflammatory nature of 
CGRP in the brain. In humans, calcitonin gene-related peptide is a potent vasodilatory neuropeptide which causes trigeminovascular inflammation and subsequently results in the sensitization of pain that is key to the pathogenesis of migraine (Natekar, Sahu, Yuan, & Nahas, 2019). During a migraine attack, levels of CGRP are elevated; therefore, anti-CGRP therapies block and reduce levels of CGRP in the brain which then mitigates and helps prevent migraine episodes.
-Gepants, a novel type of acute and/or preventative migraine treatments have been in development for over a decade that has shown promise as an effective and safe therapeutic agent. These small molecule CGRP receptor antagonists have been studied in the treatment and prevention of migraine in which early clinical trials of -gepants have demonstrated superior clinical efficacy to placebo. Their low side effect profile makes them a potentially ideal option for those with contraindications to triptans and ergots (Natekar et al., 2019). While earlier trials of -gepants revealed hepatoxicity, the latest generation of this drug class has not been associated with significant liver damage. Two later generation -gepants drugs, rimegepant and atogepant, are currently under investigation for the prevention of migraine. So far, clinical research trials on atogepant have shown promising findings, with a notable reduction in the number of monthly migraine days/probable migraine days. Based on the data from the atogepant trials, the most common side effects include nausea, constipation, fatigue, and urinary tract infection. Also, the liver safety profile for this drug was favorable, as it was found to be similar to placebo. Another -gepants drug, rimegepant, is expected to have clinical trial data ready sometime in 2020 (Natekar et al., 2019).
The current state of migraine headache treatment and prevention is promising. In the past year, several new anti-CGRP medicines were FDA-approved for the prevention of migraine. While these are effective for many, they do not work for everyone and are not always well tolerated, so there are more treatments being developed in the near future that can potentially help others who don’t always respond well to existing therapies. As previously discussed, -gepant drugs are one example of a new alternative acute and preventative treatment option that are likely on the horizon (Natekar et al., 2019). Additionally, it should be mentioned that there are a variety of preventative therapeutic agents for migraine that are early in development. Some of these include agents that target the kappa opioid receptor, the orexin receptor, acid-sensing ion channels, the oxytocin system, and more (Natekar et al., 2019). With a future that is likely to deliver more novel acute and preventative migraine treatments that are effective and well tolerated, there is no shortage of hope for those seeking effective and reliable relief from their migraine burden.
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References:
Natekar, A., Sahu, M., Yuan, H., & Nahas, S. (2019). Migraine Preventive Therapies in Development. Practical Neurology, 18(4), 54-57.