Medical Review by Dawn C. Buse, PhD

“The pain is throbbing, pulsating, stabbing. On a bad day, I have difficulty leaving my bed, let alone my home. I cannot go to work on almost half of a month, cannot enjoy playing with my children or even meeting friends for a coffee.”


Can you relate? If you are one of the many people who live with Chronic Migraine, you know how much it impacts your life. This account, written by an anonymous person with Chronic Migraine, continues:

“There are weeks during which I barely manage to keep my place in order. I feel nauseous almost all of the time and everyday odors make me want to throw up. Darkness and silence are my friends of late. I basically don’t recognize myself anymore ( ).

An estimated 11-15% of the adult population of the US meet the criteria for Migraine. And about 1-4% of those with Migraine meet the criteria for Chronic Migraine (CM). Chronic Migraine is defined by the International Classification of Headache Disorders (ICHD-3) as:

headache days on 15 or more days per month

for a period of 3 months

with at least 8 headache days fulfilling the criteria for migraine.

CM usually develops from episodic migraine (EM), which is defined as headache days less than 15 days per month ( ).

Common Risk Factors for Migraine Progression

Several sources have identified a wide range of factors that may contribute to new onset of CM. The process of developing new-onset CM from EM has been called transformation, chronification, or progression ( ).


Risk factors are broken up into two categories: those you can change and those you cannot change. Nonmodifiable risk factors (those that you cannot change) include genetic factors, female sex (prevalence largest in mid-life), Caucasian race, worse socioeconomic status, low education levels, and head injury.

Modifiable risk factors (those that you may be able to change) include medication overuse, ineffective acute treatment, headache symptoms (like allodynia, nausea), caffeine use/misuse, smoking, sleep disorders like snoring and sleep apnea, stressful life events, and comorbidities. Common comorbidities include depression, anxiety, asthma, chronic pain disorders, and obesity.

Identifying and managing your modifiable risk factors can help prevent progression to CM. It can also help bring on remission back to EM.

In a 2013 discussion called “Suboptimal Treatment of Episodic Migraine Increases Risk of Progression to Chronic Migraine,” lead study author Dr. Richard Lipton said:

“We have seen in the AMPP Study that those with episodic migraine have certain risk factors, such as headache frequency, medication use, and depression, that are associated with increased risk of chronic migraine. as treatment is increasingly optimized, the risk of progression from one year to the next declines ( ).”

Migraine progression and Chronic Daily Headache


Most people with EM do not progress to CM. Because of this, write the authors of Migraine Progression published in 2018 in the journal Headache, understanding the risk factors that predict the new onset of CM may provide insights into the mechanisms, pathophysiology, prevention, and treatment of CM ( ).

Migraine Progression reviewed all of the available scientific evidence on risk factors associated with CM progression including chronic daily headache (CDH). Studies published before March 2018 were included. CDH is defined as primary headache on 15 or more days per month for at least 3 months with attacks lasting 4 hours or more. CDH includes the diagnoses of chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache.

Risk Factors Studies: Analysis of Number, Type of Study & Strength of Evidence

The review included 17 original, peer-reviewed articles that met the study criteria – 13 longitudinal cohort studies and 4 case-controlled studies. It identified a range of risk factors for new onset of CM/TM (transformed migraine), CDH, or related chronic headache diseases.

Risk factors were grouped into clinically relevant categories and labeled in the table below (adapted from Table 3, p.24). Risk factors, the number of studies, the type of study (case-control or cohort), and the strength of evidence were each rated from fair to strong.

The strongest data support increased headache day frequency, acute medication overuse/high-frequency use and depression as potentially modifiable risk factors.

The study authors write that a lack of evidence or strong evidence for a risk factor does not mean there is not a relationship. For some risk factors, little or no research has been documented or the studies did not meet the authors’ inclusion criteria for this review.

Lead study author Dawn C. Buse, Ph.D., commented on the data, saying:


“Identifying risk factors for the new onset of CM is very useful as they give both patients and health care professionals additional targets for treatment. It is especially encouraging to identify risk factors that can be modified. The more we know about Migraine the better we can treat it-translating to more Migraine-free days, improved freedom and functioning and better quality of life for people with Migraine.”

The criteria and definition of CM and evolving case definitions for CM, TM, and CDH are mentioned as limitations of the study.

Allodynia: Risk factor or biomarker?

In Migraine Progression, researchers indicate progression from EM to CM may be linked, by a range of risk factors, to increasingly persistent activation of the trigeminovascular pathway. The trigeminovascular pathway is an area in the brain associated with the headache phase of Migraine.

They suggest this sustained activation may contribute to headache progression and central sensitization of the nervous system (sensitivity to pain and touch). Allodynia then may be an indicator of Migraine progression (or a biomarker for the pathology of sensitization), rather than a risk factor.

The role of Genes in Chronic Migraine

Your risk of progression from EM to CM and the severity of your migraine experience may also be influenced by genetic risk factors. In an interview about heredity and genetic mutations in patients with CM who predominantly report a family history of the disease, Dr. David Dodick said:


“Recently it’s been shown that the more variations an individual inherits—something called the polygenetic risk score—the more likely it is that they’re going to express Migraine as a disease, express a severe form of the disease, and the more likely it is that they’re going to express it at an earlier age. The more variations in those genes and the more genes that they’ve acquired or inherited, the more likely they are to express severe forms of the disease ( ).”

The blurry line between Episodic and Chronic migraine

Studies have documented a small percentage of people with EM (2.5%-3.1%) progress to CM each year. About 26% of people return to EM within 2 years of onset of CM.

However, in an award-winning study published in 2017, researchers from the CaMEO Study reported that there are substantial variations in the number of headache days per month within-persons with EM and CM during a 12 month period. Follow-up at 3-month intervals revealed many individuals with EM cross the less than or equal to 15 days per month CM diagnostic boundary. And nearly 75% of persons with CM will drop below this point at least once ( ).

Because of these fluctuations across diagnostic boundaries, some people with EM may have some months that look more like CM and those with CM may have periods that resemble EM.

Researchers identified four partially overlapping clinical trajectories (paths) in persons with EM:

complete clinical remission of EM or CM: an individual with EM or CM may achieve complete clinical remission, becoming symptom-free for long periods of time

an individual with or may achieve complete clinical remission, becoming symptom-free for long periods of time partial clinical remission: Migraine attacks may become less frequent, less severe and/or have fewer associated features those with CM may revert to EM, those with high-frequency EM(HFEM-10-14 headache days per month), may revert to low-frequency EM(LFEM- <5 headache days per month) and, individuals may also be reclassified with probable migraine or tension-type headache.

Migraine attacks may become less frequent, less severe and/or have fewer associated features persistence: an individual may persist without major changes in frequency, severity, or symptom profiles

an individual may persist without major changes in frequency, severity, or symptom profiles progression: some individuals may experience progression to CM(chronification). In these individuals, attack frequency may increase from LFEMto HFEM or CM, and symptom profiles and headache-related disability may increase ( ).

Preventing and Treating Chronic Migraine

Knowledge is power. Risk factors have been associated with increased headache day frequency. Increased headache day frequency is associated with greater Migraine disease burden.


Fluctuations in headache day frequency can move you across the boundary between EM and CM in both directions. Understanding your own risk factors and how they can influence the frequency of your headache days can help you be proactive about your Migraine management.

Genetic factors cannot be changed. However, three things you can discuss with your health care professional to decrease your risk of CM and promote remission to EM are:

1 – Your headache days are increasing in frequency.

A consultation with a headache specialist may be necessary to develop an effective acute and preventive Migraine treatment plan.

2 – You are taking more and more acute medication to manage your attacks and headache days

Your acute and/or preventive medication may be ineffective and you may need your treatment plan reassessed to avoid medication overuse headache. Consider adding cognitive behavioral therapy, guided imagery, meditation, and other nonpharmacological therapies to your treatment plan. Review your trigger and lifestyle management strategy.

3 – You are having difficulty managing Migraine and/or comorbid conditions like depression or anxiety.

“Whether you have episodic Migraine and want to avoid Chronic Migraine, or you have Chronic Migraine and want to improve your Migraine management, talk to your healthcare professional about these three important topics. The good news is that there is a wide range of proven pharmacological treatments, behavioral therapies, and lifestyle changes that can make a big difference, says Dawn C. Buse, PhD.

“Together you can develop a plan that may help you avoid developing Chronic Migraine and/or lower the number of days that you live with Migraine and the negative impact of Migraine on your life,” she said.


No matter where you are on your Migraine journey, understanding and addressing your personal risk factors can help you take control. More Migraine control means more freedom and less suffering. Who doesn’t want that?

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