Stephen Silberstein, MD: I’m going to talk about the comorbid conditions that are common with migraine—namely depression—because a patient walks into the office with depression and has migraine headaches and they’ll blame the migraine on the depression. I tell my patients all the time that they just have headache, they’re not depressed. You must be schizophrenic. If they had cancer and it’s eating through their bones, they weren’t depressed, there was just something wrong with them.

We know that if you have depression that somehow or other risk of migraine increases, and vice versa. As David Dodick, MD, has shown, from genetic testing it’s quite clear that the only disorder that’s associated with a psychiatric disorder is migraine. Why? We don’t know. It’s a common genetic thing that leads both; it’s not that migraine produces depression or depression produces migraine; a common biology can lead to both. Maybe it’s hypersensitivity or an increased reactivity. I don’t think we know. Perhaps migraine is a disorder of increased sensory information, and bipolar depression could be increased emotional reactivity. You need to think about anxiety, depression, and bipolar disease because, if you don’t treat your patients, they are not going to get better.

Stu, what factors can worsen or transform migraine from episodic to chronic?

Stewart Tepper, MD: For the neurologist, it’s worth remembering that we have long defined episodic migraine as being headaches occurring less than 15 times per month—generally in discrete episodes of 4 to 72 hours. And chronic migraine headaches are defined as 15 or more days per month with at least 8 days per month having migrainous features, with the duration of the attacks being at least 4 hours per day and generally for longer than 3 months. We conceive of chronic migraine as having evolved out of episodic migraine in most patients.

The advent of the data on monoclonal antibodies showing a magnitude of effect comparable between chronic and episodic migraine suggests that, perhaps, this division is not as clear as we thought. A prospective population-based study called the CAMEO trial, conducted by Richard Lipton et al., in which headache diaries were obtained every 3 months on patients with high frequency migraine, showed that patients went from episodic at 1 month, to chronic at 3 months.

Before we actually talk about a directionality of going from episodic to chronic, it’s worth considering the possibility that that border is not as hard as we previously thought. Now David’s colleague Todd Schwedt, MD, has done functional imaging that suggests that at 15 or more days per month one can reliably say that the functional imaging in a blinded manner will look different than for patients who have less than 15 headache days per month.

There is some fluidity in the way that we’re thinking about this. It’s clearly not a one-way street. We do know, thanks to Lipton’s work, that a number of clinical features of episodic migraine appear correlated with chronic migraine. One of them is actually the number of headache days per month that a person has at the beginning of a year: The more headache days that a person has, the more likely there is a transformation.

Another is the use of acute medications: As intake rises, this appears to be correlated with the transformation of migraine from episodic to chronic. Other pain conditions—obesity and snoring—seem to contribute to this transformation as well. All of these are features that are associated with transformation, many of which are remediable if not modifiable. Then we have an opportunity to talk later about people moving from chronic migraine back to episodic, with newer medications. It’s been extremely exciting to watch patients make these progressions.

Stephen Silberstein, MD: You stated the fact that the arbitrary dividing line between 15 days, more or less, is an artifact. You’re right. The other problem is that chronic migraine has so many meanings. In other disorders that means it’s been present for more than 3 months. Clusters mean it’s been present for more than 11 months. In migraine, what’s important is how many occurrences there are per month. I think the crucial issue is that there are risk factors that can help people regress back to baseline.