Conference Coverage

A Migraineur’s Headache Frequency Varies Over Time

Data suggest that transitions between episodic and chronic migraine occur more often than is understood.


BOSTON—Patients with migraine may have greater fluctuation in headache frequency than was previously understood. The rate of transition from episodic migraine to chronic migraine is higher than previously reported, and about three-quarters of people with chronic migraine have a period of episodic migraine during one year, according to a study described at the 59th Annual Scientific Meeting of the American Headache Society.

Richard B. Lipton, MD

The results suggest that headache days alone are not an adequate criterion for headache classification, said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology, and Daniel Serrano, PhD, Clinical Assistant Professor of Neurology, both at Albert Einstein College of Medicine in New York. The findings also have implications for epidemiologic studies and the design of clinical trials, they added.

An Analysis of CaMEO Data

Epidemiologic research has provided information about the profiles of people with chronic migraine and people with episodic migraine. Investigators also have clarified the frequency with which people transition from episodic to chronic migraine. Comparatively little is known, however, about individual variation in headache frequency.

Dr. Lipton and colleagues conducted a study to assess the rates of transition between episodic and chronic migraine and to model the variation in headache days over the course of one year. The investigators examined data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, which includes a representative sample of Americans with episodic migraine or chronic migraine.

Dr. Lipton’s group screened participants with an electronic version of the American Migraine Study/the American Migraine Prevalence and Prevention diagnostic module. They used modified International Classification of Headache Disorders 3-beta criteria to classify people as having episodic migraine, and modified Silberstein–Lipton criteria to classify patients as having chronic migraine. Every three months, the researchers asked participants how many days they had had headache during the previous quarter. Participants completed as many as five surveys during 2012 and 2013.

Daniel Serrano, PhD

To examine within-person change in headache frequency over time, the investigators asked about chronic migraine onset in people with episodic migraine at baseline, and asked about transition to episodic migraine in people with chronic migraine at baseline. Finally, Dr. Lipton and colleagues plotted participants’ longitudinal data and modeled them using adjusted and unadjusted generalized linear mixed models.

High Variation in Headache Days

At baseline, 15,313 respondents had episodic migraine, and 32.4% of them had episodic migraine at baseline only. In addition, 1,476 had chronic migraine at baseline, and 62.3% of them had chronic migraine at baseline only. The investigators observed a “striking level of within-person variation in headache days,” said Dr. Lipton. The number of headache days per month ranged from none to 31.

In further analyses, the investigators examined subpopulations of participants who provided data most consistently throughout the study. Of the 5,464 patients with episodic migraine at baseline for whom at least four completed surveys were available, 92.4% had episodic migraine at every follow-up. In addition, 7.6% of these participants crossed the diagnostic threshold into chronic migraine during at least one quarter. “In the American Migraine Prevalence and Prevention study, the transition rate from episodic migraine to chronic migraine was about 2.5%,” said Dr. Lipton.

A total of 526 patients had chronic migraine at baseline and completed at least four surveys. Of this subpopulation, 26.6% had chronic migraine at every time point, and 73.4% had episodic migraine during at least one quarter. “My suspicion is that the patients that we see in our practices are the people with chronic migraine that remain chronic migraine,” said Dr. Liption, “or at least that our headache practices are enriched with these people whose chronic migraine persists until we make heroic efforts to cause their headache to abate.”

A model unadjusted for covariates, but adjusted for random effects, indicated that the rate of headache days increased by 19% per quarter for participants with chronic migraine, compared with those with episodic migraine. After the researchers adjusted the model for covariates and random effects, it indicated that headache days increased by 26% per quarter for participants with chronic migraine, compared with those with episodic migraine.

Results May Influence Future Investigations

An appropriate goal of future studies would be to clarify the concept of chronic migraine, said Dr. Lipton. Allodynia, comorbidity, and treatment refractoriness are essential components of this disease and may help clarify the border between episodic and chronic migraine. Research also could attempt to identify trait predictors of episodic migraine and chronic migraine.

Furthermore, the findings suggest that the methodology of future epidemiologic studies should be reconsidered. “More frequent sampling will likely identify higher rates of chronic migraine onset,” said Dr. Lipton. The results also suggest that enrolling people with 15 or more headache days per month into clinical trials may lead to reductions in headache frequency that are unrelated to treatment, which could contribute to a strong placebo response.

On July 13, the Italian Society for the Study of Headaches recognized Drs. Lipton, Serrano, and colleagues for their research with the 2017 Enrico Greppi Award. The manuscript will be published in the Journal of Headache and Pain.

Erik Greb

Suggested Reading

Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.

Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.

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