Introduction
Migraine is a debilitating headache disorder. Including both episodic and chronic forms, it affects 14% of the population, and up to 18% of women [
1,
2]. Migraine is currently ranked by the World Health Organization (WHO) as 19th among causes for years lived with disability [
1]. Given the current barriers, improving diagnosis and optimizing treatment paradigms could substantially reduce this global burden.
Because there are no biological markers for migraine, diagnosis is based on clinical history and the exclusion of other headache disorders. Health care professionals apply clinical criteria to guide diagnoses and subsequent treatment. The definition of migraine without aura from the second edition of the International Classification of Headache Disorders (ICHD-2) requires all of the following symptoms: a) recurrent headaches (at least 5 lifetime attacks); b) untreated or unsuccessfully treated headache duration of 4 to 72 h; and c) at least two of the following pain characteristics: unilateral, pulsating, moderate or severe intensity, or aggravated by routine physical activity. In addition, the migraine attacks are associated with at least one of nausea/vomiting, photophobia, or phonophobia. Finally, other causes of headache must be excluded [
3].
Episodic migraine (EM) is characterized by those with migraine who have 0 to 14 headache days per month, while chronic migraine (CM) is characterized by 15 or more headache days per month. Specifically, revised ICHD-2 (ICHD-2R) criteria define CM as headache on 15 or more days per month for 3 or more months, of which 8 or more days meet criteria for migraine without aura and/or respond to migraine-specific treatment, occurring in a patient with a lifetime history of at least five prior migraine attacks not attributed to another causative disorder and no medication overuse [
4].
The relationship between EM and CM is complex. EM progresses to CM at the rate of 2.5% per year [
5], and CM often remits to EM (2-year transition rate of 26%) [
6]. The use of a frequency score of 15 or more days per month to classify CM is admittedly somewhat arbitrary. Nonetheless, these clinical definitions identify groups that differ in epidemiologic and symptom profiles, functional consequences and disabilities, indirect and direct costs, patterns of consultation and treatment, and rates of comorbidities. In addition, the patterns of treatment response for EM and CM differ, raising the possibility of both overlapping and distinct biological mechanisms.
Large observational studies have provided valuable information on the distinct clinical characteristics observed in CM and EM [
7••,
8••,
9,
10••]. Much of the recently published data that highlight the epidemiological distinction between CM and EM have been generated by three large observational studies: the International Burden of Migraine Study (IBMS), the American Migraine Prevalence and Prevention (AMPP) study, and the German Headache Consortium (GHC) study. IBMS is a web-based, cross-sectional, multinational survey that identified and evaluated persons with CM and persons with EM [
7••]. The AMPP study is a large United States (US) population–based, mail-based, longitudinal survey that identified 24,000 respondents with headache and followed them annually for 5 years (2004–2009) [
8••]. The GHC study is a German population–based longitudinal survey where respondents completed questionnaires via mail (
n = 4642) or phone (
n = 4708) and were identified as either CM, high-frequency EM (9–14 headache d/mo), or low-frequency EM (0–8 headache d/mo) and then evaluated on an annual basis [
10••].
Herein and with an emphasis on recent key findings, this article provides an update on the similarities and differences between CM and EM in their epidemiologic and symptom profiles, functional consequences and disabilities, indirect and direct costs, patterns of consultation and treatment, and rates of comorbidities.
Onset and Risk Factors for Progression from Episodic Migraine to Chronic Migraine
Epidemiological and clinical observations support the progression of EM to CM [
24] Progression from EM to CM occurs in about 2.5% of those with EM annually [
5]. Because not all those with EM progress to CM, it is important to identify those at high risk for progression. Risk factors can be broken into two categories: those that are easily modified and those that are not readily modifiable (eg, age, female sex, Caucasian race, low educational level/socioeconomic status, and head injury) [
25]. Identification of modifiable risk factors for progression to CM, such as obesity, depression, and medication overuse, is important because physicians can implement approaches through behavioral and pharmacologic interventions to help the patient maintain a stable, healthy lifestyle, thus reducing the risk of CM [
26]. Below are brief discussions of potential modifiable risk factors and their associations with the transition between EM and CM.
Modifiable Risk Factors
Studies have linked obesity to frequent headache [
26]. Although obesity (defined as having BMI > 30) is not a risk factor for the development of EM, it is a risk factor for progression of EM to CM [
26]. One large population-based study reported that the prevalence of CM ranged from 0.9% in normal-weighted persons to 1.6% in the obese population (OR 1.7 [1.2–2.4]) and 2.5% in the morbidly obese population (OR 2.2 [1.5–3.2]) [
27].
Depression, anxiety, and chronic pain disorders all have been associated with CM at higher rates than with EM [
8••]. It has been difficult to determine the causal relationship between depression and migraine because there is a bidirectional relationship between the two disorders; thus, those experiencing either migraine or depression are at increased risk for developing the other [
28]. To explain this relationship, two possible hypotheses are depression as a risk factor for CM onset or depression as a consequence of CM [
29]. However, recently presented results support a casual rather than consequential relationship between depression and the onset of CM. Adjusted longitudinal modeling of the AMPP study data aimed to assess the role of depression as a predictor of new onset of CM among persons with EM and concluded that, among persons with EM, severe depression was associated with an about 1.28-fold increased risk of the subsequent onset of CM the following year, even after controlling for factors of headache-related disability and headache-day frequency [
29]. Additionally, the effects of depression, anxiety, and obesity are additive, such that migraine-related disability increases when obese individuals have comorbid depression or anxiety compared to non-depressed obese migraineurs [
30,
31].
Stressful life events such as divorce, moving, employment changes, or problems with children have been considered a risk factor for chronic daily headache [
32]. Results from the frequent headache epidemiology study demonstrated that, compared to episodic headache control patients, those with chronic daily headache had more major life changes in the year before or the same year as the onset of chronic daily headache [
32].
Traditionally, acute medication overuse (generally defined as use of medications on more than 10 or 15 d/mo, depending on the class) [
5] has been considered a risk factor for poor migraine prognosis [
33,
34]. Recent epidemiological data have shown that intake of (overuse or use of) certain classes of medication increase the risk of CM in those who already have EM. Specifically, follow-up data from respondents in the 2006 AMPP study demonstrated that those with EM in 2005 had an increased risk of developing CM when they used compounds that contained barbiturates (OR 2.06; 95% CI, 1.3–3.1) and opiates (OR 1.98; 95% CI, 1.4–2.8) [
5]. The use of triptans or NSAIDs was not associated with increased risk for developing CM [
5]. These findings support other population-based [
35‐
37] and clinic-based studies [
34] in chronic daily headache.
Another possible risk factor for progression to CM is the consumption of caffeine. A population-based study that investigated caffeine consumption among participants in a general health survey determined that high medicinal (first-choice medication containing caffeine) or dietary (287 mg/d) consumption of caffeine before chronic daily headache onset was a modest risk factor (OR 1.5;
P = 0.05), with an increase in women (OR 1.9;
P = 0.006) and those who were under 40 years (OR 3.4;
P < 0.001) [
38].
Risk-factor modification, such as decreasing headache frequency with behavioral and pharmacological treatment; weight loss management; avoiding medication overuse and caffeine consumption; and screening and treating depression and other psychiatric comorbidities, remains a component to optimizing care [
26].
Acknowledgment
The authors would like to thank Allergan, Inc. for funding Imprint Publication Science (New York, NY) to provide editorial support in the preparation and styling of this manuscript.