Experts review the introduction of novel therapies available for chronic migraine prevention.
Stephen Silberstein, MD, Peter Goadsby, MBBS, and Richard B. Lipton, MD
PUBLISHED November 08, 2018
Stephen Silberstein, MD: What is chronic migraine? It’s headaches that occur frequently, many of which are severe and disabling. It’s frequently complicated by the overuse of triptans, opioids or nonsteriodals, which frequently leads to depression. There has to be a holistic approach to patient treatment. Furthermore, comorbid illnesses need to be considered. My basic philosophy is to begin someone on a preventive medicine—don’t worry about detoxifying immediately, unless they’re taking large amounts of medicines that can be harmful. Those are the basic principles, and with some of our new drugs—biologics like botulinum toxin or the PGRP [peptidoglycan recognition protein]—many of us are not going to give prevention first and detox later.
Peter Goadsby, MBBS:The development of new acute therapies has 2 goals: firstly, to maintain efficacy that we’ve seen in the triptan era and secondly, evolve safer and better-tolerated acute therapies. It’s fair to say that both the ditans, lasmiditan, gepants, rimegepant and ubrogepant have made that message. They’ve been able to develop in a way that the efficacy is maintained, the pain-free rates are reasonable, and they’re better tolerated and clearly are going to be safer because they don’t have the baggage of vasoconstriction.
For preventive therapies, what we’ve wanted are 2 things: a migraine preventive that we haven’t had until these monoclonal antibodies came along. We now have something that does what it says on the jar: a migraine drug that treats migraine; it’s also extremely well-tolerated. These monoclonal antibodies have no truly bothersome adverse effects. We no longer have patients experiencing trade-offs between their attacks or reducing their attacks with a preventive but picking up some adverse effects. Both patients and physicians have been looking forward to this moment for a long time.
Richard B. Lipton, MD: Migraine treatment includes preventive medicines that are used to decrease the frequency of headache, even in the absence of an attack, and acute medicines that are taken when the attack occurs to relieve pain and restore the ability to function—in addition to also relieving the associated symptoms of migraine, such as nausea and sensitivity to light and sound. In the 1990s, the big step forward in migraine acute treatment was the triptans. Now, that class of medication is most widely used as a treatment for migraine.
There are currently 3 new acute medications for migraine in development; 2 of them work by blocking the receptor for CGRP [calcitonin gene-related peptide], a molecule well known to be involved in the pathophysiology of migraine. One of them works as a 5-HT1F agonist, and all 3 drugs have 2 important things in common. The first is that they’re not triptans, so they may well be an effective option for the people who don’t get the treatment response they need from triptans. The second important aspect of the CGRP and 5-HT1F-targeted therapies is that they seem to be completely free of the cardiovascular liabilities that plague the triptans. People who’ve had heart attack, stroke, angina, claudication, ischemia colitis or cardiovascular risk factors are not good candidates to take triptan. There’s emerging evidence that people who don’t respond to triptans or don’t take them are more likely to receive opioids as pain relievers. We know that opioids relieve migraine on a short-term basis but worsen long-term.
Part of the reason why these new classes of medication are exciting is because they’ll give us something to offer in people who don’t respond to triptan, but also, and perhaps more importantly, something we can give to patients for whom prescribing triptans is not appropriate.
There are various evidence-based treatment guidelines for migraine in the United States, which were developed by the American Academy of Neurology] and the American Headache Society; the International Headache Society also provides some treatment guidelines.
When we look at preventive and conventional preventive medications, excluding the CGRP antibodies, there are only 5 drugs that are FDA approved for migraine that have a large body of evidence supporting efficacy. Two of those drugs are for epilepsy: topiramate and divalproex sodium. Two of those drugs are beta-blockers. And the final drug is onabotulinumtoxinA, which is FDA approved for the treatment of chronic migraines, but not for the treatment of episodic migraine.