Traditional Pharmacotherapy 
for Migraine and Headache

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Dr. Saper: No. I think that is a very thoughtful list of parameters and circumstances and it goes back to something that both Dr. Purdy and I mentioned earlier, which is that one has to tailor the treatment to the individual, and not try to make the individual fit into the treatment. One has to carefully obtain the parameters of that person’s condition, their health profile, and their vocational and life demands and find a treatment that fits that lifestyle and health profile. I think that the perspective that the Canadian Headache Society provided, just mentioned by Dr. Purdy, was clearly in that direction and achieved its goal.

Dr. Grosberg: Dr. Purdy, what is your approach to initiating and titrating pharmacologic therapy for migraine prevention?

Dr. Purdy: This is big. I think Dr. Saper already alluded to some patients “getting it” and some not. I think the way I would put it is, patients have to buy in to this therapy. In other words, they have to be fully informed and cognizant of the medication, the side effects, benefits, and all material risks, which are not insignificant.
We’re looking at preventive medications that by and large reduce a number of headache attacks per month by 50%. That variability can go higher with certain medications and lower with others, and it will vary between individuals. Patients have to know that even though they’re going on a daily medication, which they take with or without a headache, they probably are still going to need their acute medication and other lifestyle and behavioral management.

We have to explain all the reasonable side effects in reasonable terms that they can understand. We have to let them know that the side effects do occur and are expected. The historical recommendation to start a low dose and go slow is always good advice for any neurological medication. The recommendation to be careful not to stop the drug acutely or abruptly and use for at least 3 months and better for 6 or more is also sound advice.
Anecdotally, I think most things will work for headache for 3 months. If a drug can work for 6 months or longer, it probably is having a biological effect. If it works for only 3 months, then one should be concerned about the potential for placebo involvement. The next step, of course, is follow-up. It’s very important that if you put a patient on these types of medications that it be followed on a regular basis either by their primary care physician, neurologist, headache specialist, or by people who see a lot of headache patients.
But by far I think the most important thing with a prophylactic medication is to ensure that the patient understands that there is a commitment on their part and to simply take it for a few days and stop it isn’t really worth the time or effort of anybody’s involvement in their care.

Dr. Grosberg: Dr. Saper, how long do you keep patients on preventive medications for migraine?

Dr. Saper: Well, if the drug or drugs are working and without adverse effects, then I maintain them for an extended period of time, monitoring carefully for adverse effects, blood chemistry changes, etc. If the drug must be interrupted for safety reasons, such as with an ergot derivative, that requires an every-6-month drug holiday, then of course we eliminate that drug for at least a month or more. I should emphasize that monitoring for adverse effects, liver function, renal function, weight gain, etc. is important to undertake. As long as the drug is working and working effectively and safely, then I maintain the treatment.
My own experience is that most patients do not take the drug for more than 6 or 8 months, as Dr. Purdy mentioned. I do think though that it can work for up to 3 months and still not be placebo, but Dr. Purdy’s point is still a valid one and that is that very short-term value is of little value because it forces us to change drugs regularly. Many patients become very impatient with a drug that does not work for a month or more. Unfortunately, it takes longer for most drugs to work and for the proper dose to be determined.
The answer to your question is that I will keep a person on a safe and reliable drug for as long as it continues to work, and very often will have to adjust the dose or add an enhancing/complementary drug to it if it lessens in value.

Dr. Purdy: I agree with all of that. I would like to add that with the new anti-epileptic drugs, most neurologists recognize that we keep patients on anti-epileptic or anti-seizure medication for years, therefore there’s no real problem in lower dosages of these medications for a very long time, in my opinion, and I think that’s something new in the use of these particular agents. You can point out to patients that there’s probably no harm or downside to long-term use, but I totally agree that at some point during their therapeutic alliance they can come off the medication or reduce it for a few months to see if there’s any change in the biology of the underlying migraine diathesis.

Dr. Grosberg: Dr. Purdy, Dr. Saper just touched on one of the reasons why preventive medications may not work if the patient is taking it for only a month. Can you expand on why some preventive treatments for migraine prevention may not work?

Dr. Purdy: First of all, physicians can get the wrong diagnosis and so it doesn’t matter how good you are. Even the best experts in the world can get the wrong diagnosis. There are other primary headache disorders that look like migraine that aren’t. Let’s assume in the first instance that the diagnosis is correct but something isn’t working. I would challenge the physician, no matter how experienced, to reconsider the diagnosis and start over with the history from baseline.

Number two, patients could have the wrong medication or they could be taking interfering medications as noted earlier in terms of agents that interfere with prophylactic medications such as opioid analgesics and other pain killers. Side effects may be a good reason why patients don’t use the medication. Patients come off medications for three reasons; one, they don’t work, which makes sense; two, they cause side effects, which makes sense; and three, they work. Someone who’s been taking a medication for several months and says, “I’m coming off it because I don’t have any headaches,” may not realize that the medication is actually stopping their headaches.

Now, epileptic patients understand that clearly. If they come off their medication and have another seizure, that indicates that they have a seizure tendency that has to be prevented. Migraine patients who come off their medication may also get more headaches, and then they will realize the same thing. Cost is also a major factor to some patients. Finally, drug interactions are the last area that I would say cause major trouble with them not working. The majority of drugs that we use in patients today for a multiplicity of medical disorders all produce headaches.

Dr. Grosberg: Dr. Saper, for whom do you consider combination therapy where you add another preventive agent to the current one?

Dr. Saper: If a patient is not doing well or if I can’t push the dose of a particular drug higher but still want to maintain it. I may also consider combination therapy in patients in whom I think there are multiple mechanisms in play. Of the various preventive drugs that Dr. Purdy mentioned, there are a wide array of mechanisms of action, or at least presumed mechanisms of action. I don’t think we really know how some of these drugs work and every year we change our mind on how we thought they worked. Some drugs work on different channels in the neuron; some drugs work on serotoninergic, gamma-aminobutyric acid, and dopamine receptors; and some affect inflammatory neuropeptides and nitrous oxide pathways and inflammatory mechanisms.

I think that in some of the more difficult patients that we see, we have to combine multiple mechanisms of action in order to get maximum benefit. In such patients I often have a combination of preventive drugs that I use and rarely do I find myself able to treat with only one preventive agent.

Dr. Grosberg: Dr. Purdy, we’ve touched on this briefly but preventive treatments are clearly underutilized. According to a 2007 study in the journal Neurology5 nearly 38% of migraine sufferers could benefit from preventive therapy but less than half of them currently use it. How do we bridge the gap in ensuring that this subset of patients receives preventive therapy?

Dr. Purdy: I do believe in all honesty that better diagnosis will help. Recognizing the migraine diathesis, and the fact that a lot of other disorders look like migraine but aren’t such as tension headache and sinus headache, will help bridge this gap. A better understanding of the neurobiology of migraine will be important as well.
Something we don’t think about is that patients don’t always do what their doctors tell them. Patients frequently will stop taking medication even though they’re told to do so. Patients will have different perceptions of why they take the medication and they may differ from the physician prescribing them. I think patients also don’t want to take medication on a regular basis if they can’t see any benefit.
I think what happens now is that the diagnosis is reasonable and the provision of early treatment works both acutely and preventively, but the difficult part of headache, and particularly migraine therapy, is management and in particular long-term management. At one end of the spectrum we have physicians seeing patients and then diagnosing and sending them back to their primary care physicians. At the other end of the spectrum we have highly sophisticated clinics that have to deal with very complex and difficult headache problems such as the ones that Dr. Saper runs, and in between we have all sorts of variations on the theme.
The more we can get doctors to learn to manage patients rather than simply diagnose them, then I think the longer-term outlook for patients will be good. Once patients take some control of their migraines they tend to do better. I think that’s where we’re headed and I think in the next 10 years there is a large opportunity to do that.

Dr. Grosberg: Sounds excellent. Dr. Saper, is there anything that you’d like to add?

Dr. Saper: I think that Dr. Purdy has said it quite well. We have to consider the treatment of headache as an art. It is a creative undertaking. We’re dealing with an illness that is almost entirely subjective that tests the skill, creativity, and innovativeness of the physician. It is also a test of endurance because it’s an incurable but treatable condition, and various treatments must be tried and properly dosed. It’s a condition that is not completely understood from a pathophysiological point of view, and all of that goes into making the treatment a challenging exercise for both the doctor and the patient. The approach to a patient with headache is often complex and individualized but can be a very rewarding undertaking, which I know all both Dr. Purdy and I, as well as you, Dr. Grossberg, have enjoyed.

Dr. Purdy: I think that was well said. I think headache is an art and a science. The science is getting better. In the past 20 years there have been leaps in knowledge and understanding of basic pathophysiology, drug pharmacology, and neuroimaging of migraine and other related disorders, but the art is still important. For any practicing physician you need evidence but you also need experience, so the two together with the right doctor and the right patient are the magic formula.

Dr. Grosberg: Thank you both very much.