Stephen Silberstein, MD: We have written guidelines in the past for the preventative treatment of migraine. And the drugs with the best scientific evidence include most of the beta-blockers—valproate; topiramate [Topamax], the tricyclic antidepressant; and the SNRIs [serotonin and norepinephrine reuptake inhibitors], such as duloxetine [Cymbalta]. In addition, some other medications, we’re not exactly sure how well they work. So, our general concept is to pick a drug, which has been shown to be effective, that the patient can tolerate and for which there’s no contraindication. In addition to that, onabotulinum toxin type A [Botox] is now approved for patients with chronic migraine.
Most recently, there are 2 new drugs that are approved. Most of these drugs block CGRP or its receptor. And the first drug that was approved blocked the receptor. The second drug that was approved blocked CGRP itself. What’s important about these drugs is their new mechanism of action, and they can be used with patients for both episodic and chronic migraine.
Peter Goadsby, MB BS: It’s important to listen to what patients say to understand when they’re going to need a preventive. And I could say that the trigger is counting the number of days, and if you have more than 4 migraine days a month, you should have the conversation. Most people wouldn’t get into a ‘pitch battle’ about whether it was 3 or 4, what the number was. Probably more important is to stand back and try to understand what the disability is of the person sitting in front of you. Now, if they have 3 attacks a month, but their acute therapies don’t work and they’re losing time off of work or whatever it’s interrupting, that’s very bothersome for them. You listen to that. If they’re having 5 attacks a month and taking naproxen, and it works in a half-an-hour, maybe that’s not a discussion in prevention you need to have. I like to try to get inside a person’s head to understand what it is; why they’ve come to see me and how disabled they are by the problem. Because that’s really going to drive ultimately when they need a preventive, and it will drive whether they’ll actually take it.
Richard B. Lipton, MD: So, in addition to the CGRP monoclonal antibodies, there are 5 other FDA-approved drugs for the prevention of migraine and 1 additional drug that has a level of evidence that I think would make it approvable. The major medications that are FDA approved for migraine are anti-epilepsy drugs, and there are 2 of those: divalproex sodium [Depakote] and topiramate. There are 2 beta-blockers that are FDA approved. And then approved for chronic migraine only is onabotulinum toxin type A.
Approval requires at least 2 adequate-powered, well-designed randomized trial; so those drugs all have that level of evidence. There are other drugs with a little bit less evidence that have advantages that lead to their playing an important role in migraine preventive therapy. One of them is memantine [Namenda], which is a drug that’s actually FDA approved for Alzheimer’s disease. But there is evidence that it’s effective in migraine and it is free of cognitive side effects and, in fact, is used often as a cognitive enhancer. So that’s a drug that we find somewhat attractive.
Candesartan cilexetil [Atacand] is another drug which was developed for blood pressure, but that drug has 2 double-blind studies that show it’s effective. And candesartan has 2 advantages. One is a very favorable side effect profile, and the other is—as Peter Goadsby, MBBS, has shown—that in people who tried and failed other preventives, candesartan is as likely to work in those difficult-to-treat patients as it is in patients who’ve never received prevention before.
Then in addition to those agents, there are now 3 injectable CGRP monoclonal antibodies that have been approved, including erenumab [Aimovig], fremanezumab [Ajovy], and galcanezumab [Emgality], which [were] approved starting in June of 2018.
There are 3 FDA-approved devices for migraine at the moment. One of them is a form of transcutaneous electrical nerve stimulation [TENS]. The nerves that are stimulated are the supraorbital nerves. The device that provides the stimulation is called the Cefaly device, and that device was originally approved as a preventive treatment. The idea was, once-a-day for 20 minutes, you would stimulate your supraorbital nerves and that could have the benefit of decreasing frequency of headache. It’s subsequently been approved as an acute treatment as well, and there’s a 1-hour stimulation paradigm that people use at the onset of migraine to help turn off the attack. TENS is an example of what’s called the neuromodulatory therapy: a treatment that works by stimulating the nervous system to evoke a response that helps dampen down the experience of pain.
For the TENS device, I like to use it in people who don’t want to take prescription drugs. I also like to use it in people who are on prescription drugs and getting some benefit but need a boost. I like to use it in people who habitually overuse medication. So many of the acute treatments we use to relieve migraine—barbiturate-containing combination products and opioid-containing combination products—as a problem, they lead to the acceleration of headache. And so, in people who have the habit of saying, “Oh, I have a headache, I have to reach for a pill,” giving them a TENS unit gives them something else to reach for. It produces a behavioral break; it relieves the pain. In patients at risk for medication overuse or with a tendency to medication overuse, I find using Cefaly, both acutely and preventively, quite useful.
Another example of an FDA-approved neuromodulatory device, that delivers a treatment called single-pulse transcranial magnetic stimulation, is a device made by a company named eNeura, Inc. When the device is used preventatively, people apply a small device to the back of the head and push a button. It delivers a magnetic pulse that actually stimulates the brain, and that device also works both as an acute treatment and as a preventive treatment.
Then the third neuromodulatory device is vagus nerve stimulation, and that device was FDA approved in, I believe, July of 2018. It’s a device that’s been on the market for a short time. It’s approved only as an acute treatment, but it’s currently being studied as a preventive treatment. The advantage of devices is that they’re safe and they don’t have side effects in the same way that medications do. As far as we know, they don’t cause overuse syndromes the way some medications do. So, they’re really important options for people who want to avoid drugs or people who need enhanced benefit from the medications that they’re happily taking.