Current Series: Chronic Migraine: Current Treatment Options and Recent Advances

Richard B. Lipton, MD: There are a group of patients who have refractory migraine. And although people have argued about the definition of refractory migraine, if someone has tried and failed multiple treatments and is still having very frequent headache attacks, I would consider that refractory migraine.

The question to ask then the patient with refractory migraine is why the headaches aren’t getting better, and there are a number of reasons why that might occur. One reason is that you got the diagnosis wrong, that the patient doesn’t have chronic migraine but instead has another disorder that can be mistaken for chronic migraine like a daily persistent headache, or hemicranial continua. That’s an important factor to consider.

Another possibility is that the patient has more than one headache diagnosis. So occasionally patients will have both chronic migraine and another disorder, and it may be that you’ve successfully treated the chronic migraine but not the other disorder, and only by recognizing the other disorder can you formulate an effective treatment plan.

A very common reason treatment fails is that there’s an unrecognized trigger factor that the patient is experiencing. And far and away the most common unrecognized trigger is some medication that’s being overused. So doctors are very savvy about identifying overuse of prescription drugs. But caffeine containing [a] combination of ingredients, for example, may make migraine refractory because as the caffeine wears off that actually initiates the next headache.

Another reason treatment may fail is that dosing of the preventive medication may be inadequate. I will often see people who say, “Oh, I’ve tried everything,” and then they will have tried such a low dose of a beta blocker for such a short period of time that it doesn’t have a chance to work. So it’s very important on the preventive treatment side to be sure that the trial of therapy was adequate both in terms of dose and duration.

When acute treatment fails very often it’s because the patient is treating too late. And to some degree, we induce that because we say to people, “Well, you know, you can’t take this treatment more than 8 times a month, and I’m only going to give you 9 tablets a month.” And so the patient waits to take the treatment till the pain is very severe. And it may well be if they had treated while their pain was mild the headaches would have gotten better. But they wait and delay treatment and then the treatment is ineffective and we end up considering that a refractory patient.

Finally, there are patients who have comorbidities that make the disorder refractory. Migraine, particularly chronic migraine, is highly comorbid with depression, with anxiety, with panic disorder, with bipolar disease. So recognizing the comorbid disorder and treating it is sometimes part of the pathway to get the patient from stuck in a refractory state to unstuck.

Stephen Silberstein, MD: What do we mean by refractory chronic migraine? Actually, a while ago we did some investigation into the term, refractory. If you’re a general practitioner, an internist, somebody who’s refractory may have failed amitriptyline, propranolol, and a triptan. On the other extent, somebody who’s refractory for an insurance company may have failed three drugs and/or Botox to get a high on medication.

So basically, why are patients refractory? Often, they did not get the right drug, for the right amount, for the right time. Often, they may be overusing narcotics or Fiorinol or Fioricet. So, you need to find out why they’re refractory and how they’ve been treated. And those are the patients who we target for inpatient treatment.

Peter Goadsby, MB BS: I see many patients who come to me labeled with refractory migraine, refractory chronic migraine. And I start by trying to get a very clear history about what they’ve had, what medicines they’ve had, what doses they’ve had, how long they’ve had them for and about tolerability. There’s three problems I think that I see. The first problem is that the diagnosis is wrong. So, it’s worthwhile pausing and making sure they’ve got migraine. Of course, it usually is correct but occasionally you see the one-side, the person with hemicrania continua, something else is going on. So, make sure the diagnosis is correct. Number 2, when someone says that they’ve tried everything, and nothing worked, then you really need to go through the dosing because there’s a significant group of people who tried many things at half-baked doses. And what’s really failed is the way that they’ve been used. And then the third group of people have truly refractory problems.

It’s unusual not to find something to be able to do. So many people who have failed a number of medicines haven’t had neuromodulation approaches, and I particularly like using, for chronic migraine, the single pulse transcranial magnetic [stimulation]…. I will offer them procedures like occipital nerve injection. We’ll naturally have a discussion about botulinum toxin. We’ll have a discussion about inpatient care with, for example, dihydroergotamine as a way to break this difficult cycle. I think now it’s reasonable to have a discussion about the use of a monoclonal antibody, specifically about erenumab, which is now available as a treatment. So, I think that what’s happened is our options and ways of thinking and dealing with refractory migraine are really changing.