COMMENTARY

New Strategies for Medication Overuse Headache Treatment

Michael J. Marmura, MD; Hans-Christoph Diener, MD, PhD

Disclosures

October 17, 2022

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This transcript has been edited for clarity.

Michael J. Marmura, MD: Hi. I'm Michael Marmura. I'm an associate professor of neurology at Thomas Jefferson University in Philadelphia. I'll be speaking with Dr Chris Diener about the topic of medication overuse headache in patients with chronic migraine.

Dr Diener, do you want to tell us a little about yourself?

Hans-Christoph Diener, MD, PhD: I'm Hans-Christoph Diener. I'm emeritus professor of neurology and, at present, I'm the head of the department of neuroepidemiology at the University of Duisburg-Essen.

Marmura: Medication overuse headache is defined in the International Classification of Headache Disorders as worsening headache in association with acute headache medication use. For patients who take things like triptans, combination analgesics, opioids, or ergotamines, the threshold is 10 headache days per month or more. For patients taking simple analgesics like naproxen, aspirin, or paracetamol (acetaminophen), it's 15 headache days or more a month.

It's also said in the classification that if someone has medication overuse headache, if they stop taking the medication, they usually — but don't always — improve.

Dr Diener, you've written a lot about medication overuse headache. What's been your experience, and what do you think people should know about it in practice?

Diener: I'm an old man. This started for me in 1975 when I observed, for the first time, women who came to see us with daily headaches that were terrible. We found out that they took combination drugs containing ergotamine every day. When they stopped the intake, everything got worse for about a week and then they improved.

Some of them, who were older than 65 years, even became headache free or migraine free. This triggered our idea that if some people take too much acute medication, migraine can worsen and become chronic migraine. Thereafter, the International Headache Society came up with the definition of chronic migraine and medication overuse headache.

Marmura: We see it in our center all the time. I work in a tertiary headache center so we see that it's a large percentage of patients with this condition. Sometimes it's difficult to know if the medication is making things worse for patients, or they're just taking the medication because of uncontrolled migraine. Are there things that you look at in trying to make this determination in terms of whether it is the medicine?

Diener: This is very difficult. In most patients, you cannot determine what triggered this. One sign that, most probably, the intake triggers the headache is if the patients have additional dependence-type behavior or addictive behavior — for example, if they take laxatives, nasal drops, eye drops, or sleeping pills in addition to their headache medication. This is more an indication that the medication leads to the worsening of the headache.

Marmura: Sometimes it's unclear. It's almost a behavioral issue. I should say that this is more of a problem for people who have migraine, so someone who, say, takes aspirin because they have had a stroke, they're not going to start developing migraine. Has that been your experience?

Diener: That's correct. One typical example is cluster headache. We see patients who inject sumatriptan twice a day for [many] months if they have cluster headache, and they will not get chronic headache or medication overuse headache.

Marmura: I think the one exception — I believe they said this in the European Academy of Neurology guideline on the management of medication overuse headache — is that if you have a history of migraine or a family history, even if you have cluster headache, you may still develop medication overuse headache.

Diener: That's probably due to having the "migraine genes."

Marmura: There have been several studies about treatment of medication overuse and chronic migraine and addressing these different approaches. There have been some in Europe recently, and in the United States, comparing different approaches. I think the traditional approach has been to consider withdrawing the medication if you suspect that patients have medication overuse.

I think everyone would agree that education is important, that you really have to at least explain to the patient that overusing medication could potentially be worsening their headache or be the cause of their headache in some cases. Can you talk a little bit about your approach to treatment and some of these recent studies that have looked at this?

Diener: As you know, we wrote European and German guidelines for this. The first step is usually teaching patients about medication overuse — education. There are a number of randomized trials, in particular from Scandinavia and Italy, which show that this is successful in about 30% to [70%] of patients. If patients fail to get better — we changed our strategy in the past few years — then the next step is the initiation of prophylactic therapy, both medical and nonmedical.

We have now, I think, evidence for topiramate, onabotulinumtoxinA, and the monoclonal antibodies as being effective in people with medication overuse and medication overuse headache. If this fails, then the next step would be either pausing, if the drugs are not addictive like triptans, or withdrawal if people overuse opioids, which is very rare in Europe because physicians in Europe don't prescribe opioids for headache. This is very different in the United States.

Marmura: It's become a little less common. What we're seeing now is that fewer primary care doctors start patients on opioids for migraine.

There was a recent study published in Neurology looking at treatment strategies for medication overuse. In the study, they really compared just two strategies, not including withdrawal. One was to start patients on a preventive therapy and not allow them to continue taking their overused medicine, but to switch to a different medication. If a patient was taking, say, a combination analgesic, you might switch them to a triptan. The other strategy was simply to start patients on preventive therapy, along with the normal education about medication overuse, but not ask them specifically to stop their current or overused medication.

It turned out that both groups did about the same. There were some differences. Patients with anxiety didn't do as well with the switching to a new medication. Patients with a very frequent headache did a little better with switching. For the most part, both approaches were successful. This makes me think that we want to try to individualize the therapy for our patients. Withdrawal may be the best strategy for some people, but not for everyone.

Certainly, it seems like preventive therapies can be effective even in patients who have medication. We were involved in the eptinezumab studies as investigators, and we did publish some information. Did you want to talk a little bit about what we found in our patients with chronic migraine and medication overuse headache?

Diener: About 50% of the population with chronic migraine had medication overuse. Not necessarily all had medication overuse headache, which means there were a few who had headaches on 10-15 days per month. In the group that received eptinezumab, the migraine improved compared with the placebo group, and this was a big difference. There was also a reduction in the intake of acute medication.

I think this tells you that you do not always have to start with pausing or withdrawal of the medication. I think it's fair to start with preventive therapy with a monoclonal antibody, for example. If this fails, then you have to withdraw or stop the overused medication. This pausing or withdrawal is much easier if the patient is on preventive medication because the preventive medication will take away some of the withdrawal symptoms, which patients like.

There is another point. When I start to talk to a patient about this, my first sentence is always "You have to change your life; you have to start all over again." This is not only about taking medications. It's also about changing your lifestyle. You have to exercise. You have to do relaxation. You have to do stress management. We teach patients about all this in separate sessions. I think the combination of medical therapy and nonmedical therapy is really successful.

Marmura: Absolutely. Behavioral treatments — we have our patients work with a psychologist on the first visit, and then we'll have follow-up visits after that — it's very important. Sometimes people are taking medications and they don't even work. They're just taking them because they have to do something about their headaches. I think that's a real problem too. I think that education about this is very important. I think working together with patients to get them to do all these lifestyle interventions, that's very important. It's not just about the medication.

Has your practice changed because of these recent studies?

Diener: Yes, it has. This was, let's say, a very pleasant surprise that these drugs, the new monoclonal antibodies, also work in people who have medication overuse and medication overuse headache. This makes the life of these patients much, much better. Remember, the background of our first topiramate study in patients with this condition, which I did with Peter Goadsby. The hypothesis was that topiramate would not work in people with medication overuse. To our big surprise, it worked. The first study basically disproved our hypothesis. Then this result was replicated with Botox, for example, and some monoclonal antibodies.

Marmura: Yes, I agree. I think that in some ways, it's not that surprising if you think that for someone who takes something and it actually works, maybe something like a preventive therapy will work well. Whereas people who say, "Nothing works for my migraine," I almost worry more about those people.

I think I've changed much of my language about how I talk about medication overuse with patients. I never really understood why simple analgesics would make migraine worse. I'm not sure that they do, but there's often a behavioral issue, as you said.

What I don't say to patients now is, "You won't get better because you're taking this medication." Unless there's a very clear cause and effect, such as they started taking triptans every day and they're doing worse. I usually say, "This could be a problem, but I'm not sure. Why don't we treat you and see how you do?" I don't say, "You'll never get better because you're taking acute medication too often." I've changed that.

The practice is not necessarily that much different. We still do all the behavioral and nonpharmacologic therapies, but I try to use different language on how I characterize the disorder now.

Diener: I changed my language. I no longer say "withdrawal." I say "pause." It's a "pausing" of acute medication because I don't want to give people the impression that they are addicted. That, I think, makes it easier for them to accept, or at least to test whether they do better if they pause the acute medication.

Marmura: It's been a real pleasure to see these new studies come out. I think it's been really helpful. When you speak to doctors about these studies, they say that's actually what they have seen in their practice.

I will say that these studies did not really look at people who were on opioids or barbiturates on a frequent basis, so we can't really say that these studies are applicable to those patients. Those patients may need more intensive care or infusion therapies and things like that. That's the one thing we really can't comment on right now.

Thank you.

Diener: Thank you very much.

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