Migraine Progression Risk Factors: A Systematic Review

New research published in Headache® identifies risk factors for the progression of episodic migraine to chronic migraine. 

A range of risk factors have been identified for the new onset of chronic migraine (CM) or related chronic headache diagnoses among people with episodic migraine (EM) according to a systematic review published in Headache®. Dawn C. Buse, PhD, FAHS; Richard B. Lipton, MD, FAHS; and colleagues identified and summarized studies that reported on these migraine progression risk factors. Then, they determined the strength of the evidence behind them. 

Buse says she hopes that healthcare professionals and people with migraine find the review helpful. This is because it gathers existing data on risk factors associated with new-onset CM in one place. She also notes that potentially modifiable risk factors may provide areas of focus for people with migraine and healthcare professionals to potentially improve the course of the disease.

“Only a subset of individuals with EM progress to CM over any given time period,” Buse says. “Understanding the factors that predict the new onset of CM may provide important insights into mechanisms, pathophysiology, prevention, and treatment.”

The Study

Researchers summarized the findings of studies on risk factors associated with the new onset of CM, chronic daily headache or related diagnoses. Scientific literature published before March 2018 was found on PubMed and other databases. Longitudinal studies with follow-up data and case-control studies were included. Researchers reported on methodology, analytic criteria, and results for each manuscript and the review.

There were 17 studies that met the eligibility criteria for inclusion in this analysis. Researchers reviewed the strength of evidence for each of the identified risk factors using a modified version of AB Hill’s criteria for causation. Risk factors were categorized as nonmodifiable, modifiable, and based on putative mechanisms. Researchers further categorized risk factors into 5 categories: sociodemographics, lifestyle factors and habits, headache features, comorbid and concomitant diseases and conditions and factors related to pharmacologic treatment-related. They then reviewed theories of the pathophysiology underlying the development of new-onset CM or increasing attack frequency.


In summary, researchers found strong data in support of several risk factors for progression. These included increased headache day frequency, depression and use of certain acute headache medications, particularly opioids and barbiturate containing combination analgesics. Additionally, Risk factors for new-onset CM and CDH in children and adolescents were similar to those identified in adults.


Lipton, the study’s senior author, says these results need to be interpreted with caution. He notes that many of the studies were longitudinal in nature, and there may be other yet-undiscovered risk factors. Lipton adds that there is still additional work to do on genetic and epigenetic mechanisms of headache progression.  

Buse also notes that while she and her colleagues used the term “risk factors,” the causality between a risk factor and CM can not be determined in many cases. She says there are several potential relationships, but that a lack of strong evidence—or any evidence—does not mean that there aren’t relationships between certain risk factors and new-onset CM or related disease. Buse says this may just suggest a lack of research. 

“It is probable that additional risk factors exist which have not been identified,” Buse says. “It’s also possible that those that have been identified have not been studied extensively and rigorously enough, or even published.”

This review gives us hope that improved treatment for migraine is around the corner. For information on all of the latest advancements in headache medicine, visit the American Headache Society’s News page.

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