Traditional Pharmacotherapy 
for Migraine and Headache


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  • Summary:

    Dr. Brian Grosberg from the Montefiore Headache Center and the Albert Einstein College of Medicine, New York, NY moderated the topic "Traditional Pharmacotherapy for Migraine and Headache" with Drs. Allan Purdy from Dalhousie University, Halifax, Nova Scotia, Canada, and Joel Saper from the Michigan Head Pain and Neurological Institute, and Michigan State University, Ann Arbor, MI.


    The discussion focused primarily on:

    1) Acute treatment options for migraine including both non specific and specific migraine therapies

    2) first-line treatments for acute attacks of migraine

    3) comorbidities and other factors that affect acute treatment options

    4) additional factors that influence treatment decisions including the assessment of disability and migraine attack characteristics

    5) the use of algorithms for disability assessment including MIDAS and HIT-6

    6) factors that influence the failure of acute treatment options for migraines and the importance of tailoring treatments

    7) factors that influence the recommendation for secondary acute treatments/rescue therapy

    8) the importance of assessing a patient’s treatment regimen to ensure that there are no unmet needs

    9) medication overuse headaches and how to avoid them

    10) the currently available preventive treatment options for migraine including standard and complementary pharmacologic agent

    11) improving patient adherence for preventive medications

    12) patient considerations for using combination therapy.

    Med Roundtable Gen Med Ed. 2012;1(2):121–130.

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Dr. Grosberg: Migraine is a common acute and chronic neurological disorder characterized by attacks of severe headache associated with neurological, autonomic, and gastrointestinal symptoms. Frequently throbbing and unilateral, attacks are usually accompanied by nausea, vomiting, or sensitivity to light, sound, or movement. When untreated or unsuccessfully treated, these attacks typically last 4 to 72 hours. Migraine varies widely in frequency, severity, and impact on the patient’s quality of life.

A treatment plan should consider not only the diagnosis, symptoms, and any coexistent or comorbid conditions the patient may have, but also the patient’s expectations, needs, and goals. The pharmacologic treatment of migraine can be divided into preventive and abortive medications. Preventive agents are drugs that are taken on a daily basis whether or not headache is present to reduce the frequency, severity, and duration of attacks. Abortive agents are drugs that are taken to treat attacks once they have begun. Successful control of migraine in some patients may require the use of both preventive and abortive treatments.
Treatment with preventive migraine medications is necessary when migraine causes undue distress or dysfunction or the patient is at risk for clinical deterioration. Migraine preventives are now generally chosen based on clinical evidence and clinical experience or both. Choices are sometimes made on the basis of comorbid conditions, to minimize unwanted side effects, or to take advantage of potentially beneficial ones. Other considerations include cost, patient preference, convenience, and previous response to medications.

Medications for acute attacks can be divided into nonspecific and specific migraine treatments. The goals of treating acute attacks of migraine are to provide rapid and consistent relief from the pain and associated features of migraine, and to reduce the disability from the acute attacks so the overall quality of life improves. To achieve these goals, the treating physician should ensure that the diagnosis is accurate, recognize comorbidities and exacerbating factors, assess disability and attack characteristics, determine prior treatment successes and failures, understand what patients mean when they say that acute treatments “don’t work,” and then modify, monitor, and optimize treatment based on all of the above factors.

To discuss this very important topic of traditional pharmacotherapy in migraine, I have two eminent headache specialists with me today. Dr. Joel Saper is the founder and Director of the Michigan Head Pain and Neurological Institute in Ann Arbor, Michigan, and is a Clinical Professor of Neurology at Michigan State University. He is a Fellow of the American Headache Society, past president of the American Association for the Study of Headache, past chairman of the American Council for Headache Education, and an educator in the American Academy of Neurology, American Academy of Pain Medicine, American Headache Society, and the American Pain Society. Dr. Saper also has an impressive record of scientific publications that encompass all areas of headache medicine. Dr. Allan Purdy is Professor of Medicine (Neurology) at Dalhousie University in Halifax, Nova Scotia, and a Fellow of the American Headache Society. He is a past president of the Canadian Headache Society, current Treasurer of the American Headache Society, current Chair of the Scientific Program Committee of the American Headache Society, and Co-Chair of the Scientific Program for the International Headache Society in Boston in 2013. He has been the recipient of several prestigious teaching awards.

My name is Dr. Brian Grosberg. I am currently the Co-Director of the Montefiore Headache Center and the Director of the Headache and Facial Pain Fellowship Program at the Montefiore Headache Center and the Albert Einstein College of Medicine in New York.

I will begin by asking Dr. Purdy, what are the currently available acute treatments options for migraine including both nonspecific and specific migraine therapies?

Dr. Purdy: Currently we use nonspecific medication such as aspirin, acetaminophen, ibuprofen, ketorolac, naproxen, or naproxen sodium. Occasionally we use somewhat more specific therapies such as dihydroergotamine (DHE) or ergotamine, the latter being used less often than in the past, but mainly we’re now using migraine specific agents from the triptan class including sumatriptan, naratriptan, zolmitriptan, rizatriptan, eletriptan, almotriptan, and frovatriptan; there are seven in all.

Dr. Grosberg: Dr. Saper, what are your first-line treatments for acute attacks of migraine?

Dr. Saper: It varies with the patient. By the time they come to us, many patients have tried a number of standard drugs that have been mentioned by Dr. Purdy, and so we often have to begin by going through the list of drugs that have been tried and determine what works and what doesn’t work. The determination of the drug is often based on the health background and the nature of the patient’s diagnosis. The selection of a first-line drug really depends on the circumstance(s).

Having said that, for very severe headaches of a migraine-type we usually start with a triptan, and different triptans seem to work differently on different individuals. If they’ve tried all of the different triptans, we may try something that they haven’t tried, like DHE in its various forms and routes of delivery.
If it’s a more moderate headache or migraine we might try a drug such as Midrin or its primary ingredient, which is isometheptene mucate. We also find that some of our patients respond to the nonsteroidal drugs as mentioned by Dr. Purdy.

Dr. Grosberg: What you are saying is that the treatment approach needs to be tailored to each patient. Dr. Saper, how does the recognition of historical features such as comorbidities and exacerbating factors influence your acute treatment?

Dr. Saper: Well, it obviously determines what we can and cannot use. A person with hypertension, for example, certainly wouldn’t be given a drug that would raise blood pressure, such as the triptans or DHE. A person with asthma might have other limitations. In a person with a gastric ulcer or gastroesophageal reflux disease we wouldn’t want to use a nonsteroidal drug, at least for frequent use. It guides our selection of medications dramatically and so we have to balance the diagnosis, the individual patient’s health, and prior treatment successes and failures.

Dr. Grosberg: Would you like to add anything, Dr. Purdy?

Dr. Purdy: I agree with everything that Dr. Saper said but might add that it’s important to consider contraindications of known cardiovascular disease or sustained hypertension or other factors in choosing acute therapies.
Also, I tend to find that by the time patients get to a neurologist or a headache physician, they’ve used a lot of the nonspecific medications and maybe even a triptan or two. I tend to start with triptans. I think they’re quite safe. I will sometimes combine it with a nonsteroidal anti-inflammatory drug (NSAID), which helps by reducing recurrence of the headache or making the efficacy of the triptan last a bit longer.

Dr. Saper: I might also add that the best route of delivery varies from patient to patient, depending on such factors as gastroparesis or the presence of adverse effects or if the headache buildup is so accelerated that it exceeds the likelihood that an oral medicine will work. We then must resort to other routes of delivery at this point such as parenteral, rectal, or nasal spray treatments.
In addition to what Dr. Purdy said, perhaps adding an enhancing drug such as an NSAID or an antihistamine onto an acute migraine drug would be successful. We also have to consider the ideal route of delivery for that individual.

Dr. Purdy: I also think age is important. A recent trial has shown a benefit of one triptan in treating adolescents. Triptans maybe useful at equivalent doses depending on the size of the adolescent or even a slightly lesser dose. Based on severity and quickness of action, subcutaneous sumatriptan is by far the most effective triptan and quick acting. Some will appear to work better than others but, in fact, that’s always seen in practice.
At a recent meeting of the American Headache Society, a paper by Richard Lipton and colleagues suggested that switching triptan regimens or switching from a triptan regimen to another pharmacologic therapy for acute migraine does not appear to be associated with improvements in headache-related disability.1

There was a very important question posed at the time by Dr. Peter Goadsby from the University of California San Francisco Headache Center who indicated that individual cases were perhaps lost in that group data, which would be important because some patients clearly, at least from the point of view of practicing clinicians, benefited from one triptan more than another.

Dr. Grosberg: I certainly agree with what both of you have said. In addition, identifying comorbidities and exacerbating factors such as allodynia (the abnormal experience of pain in response to normally nonpainful stimuli), mood disorders (i.e., anxiety and depression), attack frequency, caffeine overuse, history of head injury, nausea/vomiting, other pain disorders, acute medication overuse, obesity, snoring, and stressful life events are crucial to providing the appropriate acute treatment.

Dr. Grosberg: Dr. Purdy, what other factors do you consider in choosing new treatments, and how does the assessment of disability and attack characteristics influence your acute treatment decisions?

Dr. Purdy: Some physicians use various tools for disability assessment. They can use the Migraine Disability Assessment Questionnaire (MIDAS) or the 6-question Headache Impact Test (HIT-6) scale, among others. I think for the clinicians who like to use this kind of information to assess disability or attacks in their patients or to compare one treatment with another, these are quite acceptable. A lot of us use calendar information, which gauges disability or headache severity on a Likert scale, and this gives us a good idea after we’ve known the patient for several months or years on how to assess that in the context of their particular case.

Dr. Grosberg: Dr. Saper, patients may report to you that acute treatments for their migraines “don’t work.” Recognizing what patients mean by this statement is key to the optimal acute treatment of their attacks. What are some examples of why acute treatments for migraines “don’t work”?

Dr. Saper: Well, I think one has to begin to understand what “doesn’t work” means by asking the patient what they mean by that statement. Is the patient referring to the amount of pain relief, the duration of the pain relief, the recurrence of pain some time later? Different patients mean different things. We might, as physicians, consider a drug to have worked remarkably well and the patient will say, “Well, it didn’t work.”
I continue to be amazed by the varying ways that phrase is used, but assuming that means that the drug was not effective in that particular individual, I think we have to look at several variables. One, was the drug taken at the right time? Did it need to be taken earlier? Was the dose proper? Dosing varies from patient to patient. Even within the same individual, headaches may vary in their characteristic features and response to acute treatments. I think there are many physiological variables that determine treatability in a given individual. One has to be very creative in responding to a patient who says, “It doesn’t work.”

We’ve talked a little bit about the issue of gastric delay or gastroparesis and the need to find an alternate route of delivery. As I’ve said, in many of my patients, most of these drugs work, but the heads to which they’re given are different. By that I mean that one really has to tailor a treatment and alternate treatments for an individual because what worked for the last headache may not work for the next headache. We have to respond to that varying degree of treatability in order to reduce the frequency with which we hear “It didn’t work.”