The Evolving Treatment Paradigm for Migraine: An Interview With Timothy R. Smith, MD, RPh (Part 1 of 2)

Timothy R. Smith, MD, RPh, is president and chief executive officer of StudyMetrix Research. He is a fellow of the American College of Physicians and the American Headache Society, a certified physician investigator of the Academy of Clinical Research Professionals, and vice president of the National Headache Foundation. Dr Smith has a special interest in patient and physician issues related to the treatment of headache in primary care. This is part 1 of an interview conducted by an editor from The American Journal of Managed Care®.

The American Journal of Managed Care® (AJMC):

What is migraine and what differentiates migraine from other types of headaches?

Timothy R. Smith, MD, RPh: Migraine is a neurologic disorder that is characterized by head pain, but it’s much more than that. It is predicated on a central nervous system sensitivity that allows events of pain and associated symptoms to take place from a pathophysiologic standpoint. It has to do with activation of the trigeminovascular system, and this trigeminovascular system activation leads to vasodilation of the meningeal vasculature, inflammation in the perivascular areas and in the meninges, enhanced pain transmission through the brain stem, and activation of higher centers. The net result is migraine attacks that are characterized by throbbing head pain that is many times on one side of the head or the other, although it can switch sides or be bilateral. Attacks are also accompanied by nausea and sometimes vomiting, and sensitivity to light and noise. Migraine attacks are aggravated by routine physical activity. One of the hallmark features of migraine is that it impairs the patient’s quality of life and functionality at least on an intermittent basis.


What age groups are most affected by migraine?

Smith: The age group that’s most affected by migraine is working age females. Children can experience migraine, but the prevalence is much lower in preadolescent children than in other age groups. In adolescence, we see the prevalence of migraine goes up considerably, especially among females. The prevalence peaks in the working years, the childbearing years—the twenties, thirties, and forties—and then with aging tends to return to lower levels, especially after menopause for females.

Overall, about 12% of the population has some version of migraine, and females outnumber males 3 or 4 to 1. Among working age females, it’s been said that as many as 18% to 20% of females in their thirties and forties have migraine syndrome.


You mentioned that migraine more commonly affects females. Is there a connection between frequency of migraine and the menstrual cycle? Is there a hormonal link? Do symptoms tend to get better or worse with pregnancy, for example?

Smith: There's definitely a hormonal linkage. It's not 100% for all women, but in general, migraine attacks can be more severe and more frequent in association with the menstrual cycle.

Most women are better during pregnancy. Their migraine frequency is less, the migraine severity is less, but we do see some women who get worse with their pregnancy, and that’s unfortunate because the treatment options are limited. With menopause, sometimes migraine can be a little worse in the premenopausal period when hormone levels are erratic, but about two-thirds of women are much better postmenopausally than in their menstruating years.


How do the symptoms of migraine affect a patient’s quality of life? How are activities of daily living and the ability to work impacted?

Smith: One of the diagnostic criteria for migraine is that the symptoms are worse with routine physical activity. Patients with migraine have this throbbing headache pain along with sensitivity to light, noise, and smells, and they have nausea and sometimes vomiting. All of those symptoms are worse when they’re up and about and trying to do something. This can be just routine activity, ambulating around the house, around the workplace, just going up and down a flight of stairs can aggravate their migraine symptoms.

Anything that restricts you from doing what you need to do or want to do is bad for your quality of life, and many studies have borne this out. The more migraine attacks patients have, the worse their quality of life.


When and where do patients with migraine typically seek care? Do they typically experience these episodes for weeks, months, or years before seeking care?

Smith: A large proportion of patients have not been to a clinic or been evaluated for their headaches by a healthcare professional. Of those that have been or do go to clinical offices or locations for care, most of the care is provided through primary care offices. Patient surveys suggest that about 60% or more of care for migraine is conducted in primary care offices—family practice or internal medicine offices. About 10% to 15% of care is provided is in neurology offices, and then there’s a very small fraction, about 2%, that go to dedicated headache clinics.

Urgent care and emergency room use is fairly common, but it’s mostly for refractory attacks. Patients may go to the emergency room if they have taken the medications that they have at their disposal and the medications haven’t worked. They may be having severe pain, they may be having extreme nausea and vomiting. In my experience, patients typically do not like to go to the emergency room because it’s not an environment that is very friendly for someone who is having a migraine attack. The bright lights, strong smells, long wait times, and sometimes chaotic atmosphere tend to make migraine attacks more difficult to bear.


How long does it typically take from the onset of symptoms until the patient receives an accurate diagnosis? Is misdiagnosis common? If so, how long do patients go misdiagnosed?

Smith: A lot of people go for a long time without getting a diagnosis of migraine. One report many years ago stated the average time to diagnosis is about 5 years. People may have failed 4 or 5 treatment attempts over the course of that time period.

Misdiagnosis is still fairly common. Perhaps as many as half the people who have been to a medical setting and had a medical interview for their headache diagnosis came away with an inaccurate diagnosis. One of the common misdiagnoses is the so-called sinus headache. Pain from the sinuses without infection is exceedingly rare, so the notion of debilitation due to sinus pain is a common misconception. Also, sometimes we see people get misdiagnosed with tension headache or sometimes patients will be erroneously diagnosed with stress headaches or hormonal headaches.


What are some of the barriers that patients encounter when they seek care?

Smith: In terms of barriers to care, being uninsured is obviously a problem. I think that most patients have access to good primary care doctors. However, some patients who need more advanced care—for example, those who live in smaller communities or more rural areas—may not have access or easy access to specialists or headache clinics. That is a concern. I think advances in telemedicine are starting to address this issue in some areas.

Other barriers to care have to do with access to medications. Again, being uninsured is a problem. Some of the more recently approved treatments are more expensive, and that makes it difficult for indigent or uninsured people to be able to afford them. Also, insurance coverage limitations and other policies may prevent patients from getting access to effective therapies.

Also, I think that in some communities and in some practices, some clinicians don’t take migraine management very seriously. Those clinicians may deal with migraine more passively and may not partner with patients very well to help them find effective therapies. An example of that would be not using biobehavioral interventions. It can be challenging for patients to afford or get access to healthcare professionals who can train them in biofeedback and other biobehavioral interventions—it’s an unmet need. Those are some of the obstacles or barriers to care as I see it.

AJMC®: What is the role of primary care providers in diagnosing and managing migraine? When should a patient with migraine be referred to a specialist?

Smith: In my opinion, migraine is a mostly a primary care illness. It is a highly prevalent, highly disabling disorder. We have a better understanding of pathophysiologic mechanisms, and there are good treatments out there that work. I think primary care doctors are perfectly capable of providing excellent care to most patients with migraine.

Certain patients may need to be referred to neurologists who specialize in headache management. The patients who have difficulty getting their headache frequency down, who have failed more than 1 or 2 prophylactic medications, who are using lots of abortive therapies, who are burning through the triptans every month—those patients may benefit from a referral to a specialist. The specialist can work out a plan with rational polypharmacy, for example, and then incorporate biobehavioral techniques and sometimes physical medicine techniques into the treatment plan, depending on the symptoms. Some patients need that kind of multimodal approach.

A small group of patients with severe symptoms sometimes would benefit from treatment in an inpatient setting.