Traditional Pharmacotherapy 
for Migraine and Headache

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Dr. Grosberg: For which patients do you consider prescribing a secondary acute treatment or a rescue therapy?

Dr. Saper: Most of them. I’m pretty much convinced that no drug that we have available to us is consistently reliable from headache to headache, and that all patients need a backup not only for a rescue drug but perhaps even an alternative drug. I mean, many of the patients who I’ve treated over time have had, let’s say, a triptan or, as Dr. Purdy mentioned, a short-acting triptan together with a long-acting triptan.
Many of the patients who I’ve treated, I’ve given—not to be used on the same day or within the same 24 hours—a triptan for certain types of headaches and DHE for other kinds of headaches. For example, in women with menstrual headache, the headache may respond entirely different to one treatment than a headache at another time of the month; so, there has to be that kind of creative prescribing to bring the maximum satisfaction to some of these patients.

Dr. Grosberg: Dr. Purdy, you touched briefly on the recent study by Dr. Lipton about switching triptans, and we know that acute therapy decisions are almost always about switching treatment. How do you assess the patient’s current treatment regimen to ensure that there are no unmet needs for treatment?

Dr. Purdy: Well, I think that the information from the Los Angeles meeting is quite pertinent because it brings up some very interesting thoughts of why switching from one triptan to another doesn’t necessarily result in better efficacy or outcome. All clinicians see quite a difference in treatment at times and that was the point I believe that Dr. Goadsby was making, that possibly individual cases would be lost in the data. Also, we have to acknowledge that there are many reasons people switch medications.

I think in quick summary there may be several points that can be made. Patients switch triptans to see if others work. In other words, patients may switch medications because they think that if they take the medication earlier in the migraine attack then maybe that would get them back to their normal state. They may have to increase the dosage or they add an NSAID, as I indicated earlier.
Is the effect of their triptan consistent? In other words, sometimes, as Dr. Saper pointed out, the same patient may have migraine with aura one day or without aura another, or a moderate migraine one day and severe another, and they’re looking for a consistent response. We do know that certain triptans will do that for some patients. It’s hard to predict who will respond, so if there is a consistency need, it may be necessary to switch treatment or, again, treat early.

Recurrence is a big problem, and again treating early might help. There are two evidence-based triptans, eletriptan and frovatriptan, that seem to have lower recurrence rates, and therefore should be considered. Although, every practicing clinician knows that patients are different, so, again, all other triptans should be tried in due course.
Side effects are a major problem resulting in the switching of medications. Treating early, possibly reducing the dosage if there are major side effects, or trying something different such as almotriptan or frovatriptan, which seem to have a lesser side effect profile, are possible options.

Finally, there’s a global view addressed by Dr. Lipton and his colleagues that patients still aren’t totally satisfied with the overall care of their acute migraine although they’re getting the right medications. In that instance, he and his group justifiably point out that other things may be incorporated into their treatment, including behavioral therapy, nonmedical therapy, or complementary therapies. An alternative approach is to discuss the expectations of the patient. What is their view? Do they expect to be totally headache-free? What is the outcome they wish to achieve? I think that’s the end point patients look at which is not necessarily what we look at in clinical practice or in randomized trials.

Dr. Grosberg: Excellent. Thank you. Dr. Saper, what is the concept of headache caused by medication overuse and how does one go about avoiding it?

Dr. Saper: Well, medication overuse headache (MOH) is the phenomenon by which an increasing number of headaches occur in conjunction with an increasing amount of certain types of abortive or rescue medications. In 1983, I published findings that the frequency of medication use that exceeded 2 to 3 days a week, on a consistent basis over an extended period of time, would set an individual into the course of developing an MOH,2 and 25 years later the International Headache Society came forth with parameters based on monthly usage of medication that essentially calculated the same numbers.
I like the definition of per-week usage because technically a person could use a lot of the drug in the first several parts of the month and none of the drug for the rest of the month, so they would not be as likely to be caught in the MOH phenomenon as they would be if they used it regularly and dependably. Having said that, the only way to prevent headache associated with medicine usage is to limit the use of drugs that can cause it to a frequency of less than 2 to 3 days a week of usage, week after week, month after month, or based on a monthly calculation of 10 to 12 tablets of varying forms.
I think that one of the problems in our approach to MOH is that we fail to recognize that not everybody who has bad headaches will overuse their medicine and that a behavioral component is a very important part of the underpinning of the person who develops MOH. So, the treatment of MOH is not simply about prevention, but of how much drug the doctor gives and the frequency of visits so as to allow the physician to monitor the drugs that are given. In addition, the physician should take a proactive stance on recognizing personality and psychological features of an individual that are likely to lend themselves to the MOH over-usage pattern.
I think that in both prevention and acute treatment, the combination of the physiological and the psychological side of care has to be considered.

Dr. Grosberg: I’m now going to segue into preventive treatment for migraine and I’m going to ask you, Dr. Purdy, if you can tell me what the currently available preventive treatment options are for migraine including the standard pharmacologic agents and the complementary options as well.

Dr. Purdy: Well, for standard pharmacologic agents there are basically six classes. Historically, beta-adrenergic antagonists have been used for the treatment of migraine based mainly on serendipity initially, and some trial data later. Tricyclic antidepressants in low dosages can be quite helpful in the management of prevention of migraine headaches.
Selective serotonin reuptake inhibitors may be helpful in some patients. They are used particularly if there are other comorbid disorders such as anxiety and/or depression. Calcium channel blockers have also been used for migraine prevention and there is some benefit associated with their use. There is country-specific availability of calcium channel blockers, such as verapamil, and they have been used quite successfully. Recent guidelines from the American Heart Association/American Academy of Neurology (AHA/AAN) can be helpful here in looking at the literature.
Serotonin antagonists can also be used. I believe there is one formulation available in the United States, which Dr. Saper alluded to, and the most powerful of all the serotonin antagonists is methysergide, which is generally not available in the North American market at present.

The biggest and latest group of drugs that seem to be very effective in preventing migraine are the anti-seizure agents. This group of medications seems to have a commonality in how they treat headache and how they may affect the actual pathophysiological properties of the disorder, which is supported both clinically and by basic science research.
Today any new anti-epileptic medication that comes on to the market will probably be used for migraine rather quickly. Migraine and epilepsy, of course, share similar mechanisms and both episodic disorders require intermittent and continuous therapy.

Dr. Grosberg: Can you tell us about some of the complementary options or non-oral formulations of prevention?

Dr. Purdy: Yes. There are several formulations that are currently available including vitamins such as riboflavin, enzymes such as coenzyme Q10, and other treatments such as butterbur. I personally don’t use a lot of these on a regular basis because by the time the patients come to see me they’ve most likely tried many of these options and none seem to help too much. Again, coenzyme Q10, butterbur, riboflavin, and magnesium have been shown to be quite useful in some patients and in some settings, with some limited data to support their usage; certainly not at the level of a randomized clinical trial for most of these agents.

Dr. Grosberg: Dr. Purdy, who in your opinion needs preventive treatment for migraine or would benefit from it?

Dr. Purdy: Well, I think that there are variations on this. I think it depends on from whose point of view. When the patient perceives that they have a major problem with headache despite acute therapy, I think that’s an indication. I don’t think we’re at the stage in epilepsy where a patient has a single isolated seizure and declares they don’t want any more that one can fully understand the desire not to have a generalized seizure in a work place or otherwise.
But migraine patients do not really want to tolerate a lot of headaches. Traditionally it was more than three headaches a month, or four moderately severe episodes, that were considered frequent. Also, if they start to overuse medication, as Dr. Saper mentioned, such as opioids or other analgesics, they run the risk of developing MOH. In that setting they may be wise to cut back on those particular types of medications and use a preventative medication supported by an acute medication.

I think there are no absolute data in this area, but looking at the classification and clinical practice, if patients start to use acute medications more than 8 days a month, which constitutes about 2 or 3 days a week, then I think they’re in a situation where they should consider the use of preventative agents. Even the triptans, of course, can produce MOH.
I believe it is partly individualized but it’s becoming clearer and clearer that what patients may be doing is using triptans two or three times a month in the hopes of avoiding daily medication, with an efficacy rate somewhere in the range of reducing 50% of the headaches. Therefore, these options are open to them and it becomes very individualized in most cases. But those are general guidelines that most doctors use.

Dr. Grosberg: Dr. Saper, touching on what Dr. Purdy just said, what are the goals in preventive treatment for migraine and how do you communicate realistic expectations of the selected medication to patients?

Dr. Saper: Well, the goals would be to either reduce the frequency and intensity of the existing headaches or, and I think all of us have seen this clinically, to enhance the efficacy of the abortive or rescue medicines. Early on in our history of treating headaches with beta-blockers and tricyclics, which Dr. Purdy mentioned in his list of available preventive drugs, we began to see that many of the patients who did not notice a dramatic reduction in frequency, intensity, or disability were nonetheless reporting that their abortive/rescue medicine actually worked better when they were taking the preventives. It’s almost as though the preventives were opening the door a bit so that the abortive would work.

I think that one of the points that should be emphasized to patients is that while we want to improve the quality of their life by reducing the frequency and intensity of the headaches, we also want to enhance the treatability of an inevitable breakthrough headache.
So it’s very important to describe to a patient that these are our goals but that we can’t achieve those goals in everyone. It should be explained that we need to try for a sustained period of time with every drug and that these drugs work slowly. They don’t necessarily work overnight or over a weeks’ time. The dose must be determined. There is no set dose for most of these drugs, and we may have to combine the drugs for synergistic benefit. Some patients understand this and appreciate it, while others don’t.

Dr. Grosberg: Dr. Purdy, how do you decide which medications to prescribe for individual patients in the context of recognizing the historical features such as comorbidities and exacerbating factors?

Dr. Purdy: Actually, I must allude to a recent publication by the Canadian Headache Society in our journal on guidelines to manage migraine and strategies.3 This was mentioned in a recent article in Headache authored by Elizabeth Loder and colleagues in a review of American Headache Society guidelines compared with Canadian Headache Society guidelines.4 They list several areas and various strategies that we put together.
A first-time strategy for new patients historically has included beta-blockers and tricyclics; a low side effect strategy, which includes complementary treatments, such as magnesium, coenzyme Q10, butterbur, riboflavin, or feverfew; increased body mass index strategy, which generally today would include topiramate, because there are very few preventive agents that don’t produce weight gain; hypertension strategy, with beta-blockers; depression strategy, amitriptyline or selective serotonin re-uptake inhibitors; a refractory strategy, which is an approach that uses two medications, as alluded to by Dr. Saper, possibly with different pathophysiologic mechanisms or different ways of working such as a beta-blocker and tricyclic; and pregnancy and lactation strategy, which is to avoid most medications and make sure they’re safe. I suppose we could also include strategies for menstrual migraines.
These are the kinds of strategies that one can determine for various groups, and this is very useful for doctors and patients.

Dr. Grosberg: Dr. Saper, do you have anything to add to this?