Migraine is a disabling headache disorder that is underdiagnosed and undertreated worldwide, which may be partially attributed to misdiagnosis and patients' expectations of poor treatment outcomes.1 The prevalence of migraine in the United States has been stable for over 20 years, around 11.7% to 13.2%.2-4 Chronic migraine (CM) represents approximately 7.7% of individuals with migraine, with a U.S. prevalence of approximately 0.9%.5 The purpose of this article is to provide a review of CM, including pathophysiology, burden, diagnosis, and management, with special emphasis on the role of NPs.
The International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3b) includes diagnostic criteria for CM among the primary headache disorders, a category that includes migraine, tension-type headache, trigeminal autonomic cephalalgias, and other primary headaches.6 Migraine is subclassified as migraine without aura, migraine with aura, and CM. Individuals with migraine without aura experience recurrent attacks with symptoms that include unilateral, pulsating pain of moderate/severe intensity, which worsens with routine physical activity and is accompanied by nausea and/or light/noise sensitivity.6
In addition to typical migraine symptoms, migraines with aura are distinguished by recurrent, slowly developing attacks with lateralized and reversible visual, sensory, speech/language, motor, brainstem, or retinal symptoms; attacks are accompanied or followed by headache and migraine symptoms.6 This aura phenomenon may be explained by a propagating wave of depolarization followed by neural suppression, known as cortical spreading depression.
Clinical understanding and the definition of CM have evolved over time. In ICHD-3b, CM is broadly defined as migraines experienced greater than or equal to 15 days/month, noting that besides increased frequency, it is impossible to distinguish individual episodes of migraine in patients with CM from the headaches with migraine characteristics experienced less than 15 days/month in patients with episodic migraine (EM) (see Distinguishing features of EM and CM).6
As defined by ICHD-3b, secondary headache disorders are characterized by headaches caused by another condition (for example, head/neck trauma and comorbid medical conditions).6 Headache disorders not qualifying as primary or secondary include painful cranial neuropathies, other facial pain, and other headache disorders.6
Risk factors for migraine progression
Given that attack frequency is the driving distinction between CM and EM, an individual patient may change categories; recently, the Chronic Migraine Epidemiology and Outcomes (CaMEO) study found that over a 3-month period, 3.4% of patients with EM progressed to CM, and 49.9% of patients with CM improved to EM in a large sample representative of U.S. patients receiving routine care.7 Several nonmodifiable risk factors are associated with migraine chronification.8 Epidemiologic studies repeatedly show that women have a higher CM prevalence than men, prevalence peaks in midlife for both genders, and is lower among adolescents and those older than 50.5 CM is also highest among those with the lowest income, and full-time employment rates are lower among those with CM.9 CM is also most prevalent among White and Hispanic individuals.9
Identified modifiable risk factors for migraine progression include high-frequency headache, medication overuse, poor treatment efficacy, comorbid pain, psychiatric comorbidities, obesity, excessive/habitual caffeine intake, sleep-related breathing disorders, and stress; risk mitigation interventions may prevent chronification.10,11 Among individuals with EM, the odds of developing CM increase with headache frequency by nearly 25-fold for those with the highest versus lowest headache frequency.12 Individuals with high-frequency headaches should treat them early during the attack, before the onset of sensitization, to decrease attack frequency and intensity.13
CM development is associated with overuse of certain medications (notably opioids and barbiturates, but also serotonin 5-HT1 receptor agonists [triptans] and nonsteroidal anti-inflammatory drug [NSAIDs]). The risk of CM development grows with the increasing number of acute medication days; however, for NSAIDs, the risk of migraine chronification is limited to patients experiencing 10 or more headache days per month.14 Poor acute treatment efficacy and ineffective medication overuse can contribute to migraine chronification.10 Analyses from the American Migraine Prevalence and Prevention (AMPP) study found that analgesic or NSAID users reported high treatment efficacy less frequently than triptan users.10
Comorbidities associated with migraine occur more frequently with CM. Prevalence of comorbid pain (for example, from chronic pain disorders, such as fibromyalgia, osteoarthritis, or chronic fatigue syndrome) increases with migraine frequency, as does the proportion of individuals reporting severe pain, even within EM and CM classifications.7,9,15 Psychiatric comorbidities, including anxiety and depression, are common among individuals with CM and are risk factors for migraine chronification.9,16 Patients presenting with migraine should be assessed for psychiatric comorbidities and given appropriate treatments for their condition.13 The prevalence of CM increases with body mass index; obesity incidence is higher in this group compared with EM.17 Data suggest weight reduction may reduce headache frequency; however, evidence-based recommendations are lacking.13
A case-control study of individuals with episodic (2-104 headache days per year; n=507) and chronic daily headache (greater than or equal to 180 headache days per year; n=206) determined the association between caffeine consumption (dietary and medicinal) and chronic daily headache.18 Current caffeine consumption was higher among individuals with migraine than those with nonmigraine headaches, and high caffeine intake was associated with chronification.18 Caffeine use induces withdrawal headache, defined in ICHD-3b as a headache that develops equal to or less than 24 hours after cessation of regular (greater than 2 weeks) consumption of greater than or equal to 200 mg/day caffeine (approximately 2 cups of coffee) and that resolves 1 hour or less after a 100-mg caffeine intake or 7 days or less with continued abstinence.6 Experts recommend slowly tapering off caffeine over several weeks to avoid withdrawal headache.13
Sleep-related breathing disorders (for example, snoring and sleep apnea) are also risk factors for chronification.13 Encourage improved sleeping habits by suggesting weight loss, smoking cessation, decreased alcohol consumption, and avoiding sedative medications. Referral to a sleep specialist to diagnose and manage primary sleep disorders should be considered.
Stressful life events are also a risk factor for migraine chronification.19 Major life events, such as changes in work, relationships, or residence; illness or death of a family member or friend; or personal stressful situations are associated with the development of chronic daily headache and migraine. Stress identification and modification, through counseling and mental healthcare provider referral, are integral to effective CM treatment.
As migraine attacks increase in frequency, associated symptoms may decrease in severity and frequency.20 This transition to more frequent attacks is thought to signify a change in underlying pathophysiology, which is attributed to a sensitized central nervous system (CNS). History and physical exam of patients with CM is notable for cutaneous allodynia, a clinical marker of central sensitization. Patients with cutaneous allodynia perceive normally innocuous stimuli as painful, consequent to hypersensitization of the CNS along the trigeminal nociceptive pathway.21
Although the precise locus of sensitization and causal relationship between allodynia and migraine chronification is not identified, preclinical migraine models replicating allodynia symptoms suggest that recurring migraine attacks may induce central sensitization with resultant cutaneous allodynia.22 CNS hypersensitization lowers the threshold for initiating a migraine attack, potentially increasing attack frequency and damaging the periaqueductal gray matter. This perpetuates the CM disease state with subsequent poor pain modulation and treatment refractoriness.20,23
The degree of headache-related burden associated with EM and CM varies. Because more than half of a chronic migraineur's days are spent with pain and symptoms, those with CM may experience increased headache-related burden across several domains (see Burden of EM and CM).
Multiple epidemiologic studies, including the CaMEO study, the International Burden of Migraine Study (IBMS), and the AMPP study reported higher rates of headache-related disability among individuals with CM than those with EM, as measured by the Migraine Disability Assessment (MIDAS) questionnaire.5,9,16,24 The MIDAS is a patient-assessed, 5-item questionnaire that quantifies headache-related reduction or loss of activity among three domains: schoolwork/paid employment, household work/chores, and nonwork–related activities (family, social, and leisure). Higher scores are associated with greater disability. Greater disability associated with more severe disease can have a negative impact on functionality and activities of daily living, such as work, household chores, and social relationships.9,25
The substantial disability associated with migraine affects work productivity, routine chores, and relationships—especially for those with CM.24,26 In the CaMEO study, results from the Family Burden Module found migraineurs and their partners reported a pervasive and significant impact of migraine across the domains of reduced participation in family events, missed/cancelled events, financial impact, and interactions between migraineurs, their partners, and their children. In addition, impact severity increased with migraine frequency, and migraineurs consistently perceived the impact to be greater than their partners did.27
Quality of life
Detriments to quality of life are prevalent among those with CM and are commonly measured with the Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1.9,28 The MSQ is a 14-item questionnaire that categorizes migraine-related detriment to activities of daily living across three domains: role restrictive, role preventive, and emotional functioning. Scores range from 0 to 100, where a higher score indicates a greater quality of life.29,30
In the PREEMPT clinical trials, participants (all with CM) had low baseline health-related quality of life scores, indicating that migraine restricted and prevented social and work-related activities and adversely affected emotions.28 The IBMS Study found worse migraine-specific quality of life among those with CM than those with EM.9
Barriers to medical care
In CaMEO, less than 5% of individuals with CM and headache-related disability successfully overcame three identified barriers to medical care for their condition: consulting a healthcare professional (HCP), receiving an accurate diagnosis, and receiving minimal acute and preventive pharmacologic treatment.31 CaMEO also found that individuals with CM who consulted a headache specialist were more likely to be diagnosed with CM than those consulting other types of HCP, although the diagnosis rate was still low (36.0%). The rate of CM diagnosis was 15.8% among patients who consulted nonheadache specialist prescribing HCPs.32
Healthcare resource utilization
Healthcare resource use is substantial, and higher for those with CM than EM.33 The IBMS and AMPP studies found a higher frequency of HCP visits among those with CM.9,34 The AMPP study found that those with CM reported a higher average frequency of use of most common headache-relieving drugs than those with EM.34 Increased healthcare resource use translates into increased costs for those with CM.34
Patient history. A comprehensive patient history and physical/neurologic exam are important to rule out secondary causes of migraine (head trauma, systemic disease).35 Attack frequency and duration are essential components of a migraine diagnosis; however, the number of headache-free days may provide a more accurate estimate.36 Headache diaries are preferred to patient recall for capturing attack frequency and headache duration as well as other important factors, such as headache triggers and medication response.36 Inquire about comorbidities, other areas of pain, HCPs consulted for pain/headache, and treatment history for a complete medical history.
Physical exam. New patients should receive a thorough physical exam to determine any deficits that may be contributing to the patient's headaches (hypertension, heart murmur, cervical dystonia). Continued follow-up care establishes improvement or decrements in contributing conditions. Refer patients to specialists as needed.
Role of imaging. Headache experts discourage imaging studies in patients with stable headaches meeting migraine criteria outlined in the ICHD-3b. Evidence has shown that the incidence of imaging findings is not different among patients with migraine and those without migraine, and therefore, should not be used as a diagnostic tool.37 Instead, migraine diagnosis relies upon a detailed patient history and medical/neurologic exams.38
Differential diagnosis. To diagnose CM, experts recommend initial elimination of secondary headache causes by identifying red flags, such as sudden symptom onset, worsening of preexisting headache in the absence of risk factors, and presence of systemic illness (cancer, HIV, lupus erythematosus, arteritis).35,38,39 Applying ICHD-3b criteria then classifies symptoms as a primary headache disorder followed by the appropriate diagnosis within that classification.38 Prevalence of headache subtypes (and in turn the frequency that one can be expected to encounter in these patients) can also aid in differential diagnosis.
While the prevalence of migraine has been reported to be 11.7%, other types of headache have much lower prevalence rates, including chronic tension-type headache (2%), cluster headache (0.4%), and hypnic headache (0.07%).3 New daily persistent headache, hemicrania continua, and paroxysmal hemicrania all occur rarely.35
NPs can help their patients identify potential lifestyle adjustments in their treatment protocol to help reduce the risk of migraine progression (see Treatment options for migraine).35,36 All patients with migraine should have access to acute pharmacologic treatments;36 patients with CM also require preventive treatment.31 The American Headache Society (AHS) provides recommendations for acute and prophylactic migraine medications (www.americanheadachesociety.org/professional_resources/practice_parameters_guidelines_and_classification).40,41
The AMPP study found a large underutilization of prophylactic migraine medication (indicated for 39% of migraineurs, but used by 12%), representing an area for great potential impact.3 Only one drug, onabotulinumtoxinA, is approved specifically for CM prophylaxis. The safety and efficacy of onabotulinumtoxinA for CM prophylaxis have been demonstrated for up to nine treatment cycles.42-44 OnabotulinumtoxinA has also been shown to improve patient quality of life, as early as 12 weeks (one treatment cycle).28 All NPs qualify for training to perform onabotulinumtoxinA injections.45 Even for NPs who do not inject, knowledge of the injection process can help educate patients regarding realistic treatment outcomes and appropriate provider referral for injection and/or other strategies for management.
Complementary and alternative treatment use is high among those with migraine/severe headache.46 American Academy of Neurology/AHS guidelines recommend (Level A evidence: medications with established efficacy) butterbur for migraine prevention, and recommend considering (Level B: medications that are probably effective) feverfew, magnesium, and riboflavin.47 Other expert-recommended nutraceutical options include coenzyme Q10 and B vitamins.48
Not all patients will respond favorably to treatment; patients with severe baseline pain, long headache duration, nausea, psychologic disorders (anxiety, depression), and acute medication overuse often have poor treatment response.49-52 A detailed patient history should alert the NP to any of these characteristics so they may be addressed and treatment adjusted accordingly.
NP role in patient management
NPs knowledgeable about diagnostic criteria for EM and CM and evidence-based treatment strategies reduce two barriers critical to positive patient outcomes.36 With CM, complete pain relief may not be achievable; therefore, NPs play a key role in educating patients regarding treatment adherence and expectation management.36 Counseling patients regarding medication options, reducing medication overuse, lifestyle choices, trigger management, and the importance of keeping a detailed diary of headache intensity, frequency, and duration is essential.
Collaboration between NPs, headache specialists, mental health providers, and pain specialists ensures that comorbid disorders are addressed in conjunction with headaches, with timely follow-up to address new symptoms or changes in headache. Special consideration should be given to patients with hemiplegic migraine, migraine with aura, and mixed migraine, as well as pregnant women with migraine.
CM represents an area of growing interest and research with increasing knowledge of the burden it places on individuals and society. Novel biologic drugs targeting calcitonin gene-related peptide are in early clinical development for CM treatment.54 Ongoing migraine databases collect information on populations that cannot be studied in controlled trials; databases may collect enough information to demonstrate that certain treatments in these populations are safe. Evolving patient support systems include websites where clinicians, family, and friends can offer empathetic feedback in a virtual extension of face-to-face patient groups. The authors believe that NPs are well positioned to provide increased support and improved outcomes for patients with CM.
1. Miller S, Matharu MS. Migraine
is underdiagnosed and undertreated. Practitioner
. 2014;258(1774):19–24, 2-3.
2. Victor TW, Hu X, Campbell JC, Buse DC, Lipton RB. Migraine
prevalence by age and sex in the United States: a life-span study. Cephalalgia
3. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine
prevalence, disease burden, and the need for preventive therapy. Neurology
4. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine
in the United States: data from the American Migraine
Study II. Headache
5. Buse DC, Manack AN, Fanning KM, et al. Chronic migraine
prevalence, disability, and sociodemographic factors: results from the American Migraine
Prevalence and Prevention Study. Headache
6. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia
7. Scher AI, Lipton RB, Fanning KM, Largent J. Pain Comorbidities of Episodic and Chronic Migraine
: Results from the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study. Paper presented at: 67th Annual Meeting of the American Academy of Neurology (AAN); April 18-25, 2015; Washington, DC.
8. Cho SJ, Chu MK. Risk factors of chronic daily headache or chronic migraine
. Curr Pain Headache Rep
9. Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine
Study (IBMS). Cephalalgia
10. Lipton RB, Fanning KM, Serrano D, Reed ML, Cady R, Buse DC. Ineffective acute treatment of episodic migraine
is associated with new-onset chronic migraine
11. Scher AI, Midgette LA, Lipton RB. Risk factors for headache chronification. Headache
12. Katsarava Z, Schneeweiss S, Kurth T, et al. Incidence and predictors for chronicity of headache in patients with episodic migraine
13. Bigal ME, Lipton RB. Modifiable risk factors for migraine
progression (or for chronic daily headaches)—clinical lessons. Headache
. 2006;46(suppl 3):S144–S146.
14. Lipton RB, Serrano D, Nicholson RA, Buse DC, Runken MC, Reed ML. Impact of NSAID and triptan use on developing chronic migraine
: results from the American Migraine
Prevalence and Prevention (AMPP) study. Headache
15. Buse DC, Manack A, Serrano D, Turkel C, Lipton RB. Sociodemographic and comorbidity profiles of chronic migraine
and episodic migraine
sufferers. J Neurol Neurosurg Psychiatry
16. 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
17. Bigal ME, Lipton RB. Obesity is a risk factor for transformed migraine
but not chronic tension-type headache. Neurology
18. Scher AI, Stewart WF, Lipton RB. Caffeine as a risk factor for chronic daily headache: a population-based study. Neurology
19. Manack AN, Buse DC, Lipton RB. Chronic migraine
: epidemiology and disease burden. Curr Pain Headache Rep
20. Bigal ME, Lipton RB. Concepts and mechanisms of migraine
21. Bigal ME, Lipton RB. Migraine
chronification. Curr Neurol Neurosci Rep
22. Boyer N, Dallel R, Artola A, Monconduit L. General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine
23. Bigal ME, Lipton RB. Modifiable risk factors for migraine
24. Bigal ME, Serrano D, Reed M, Lipton RB. Chronic migraine
in the population: burden, diagnosis
, and satisfaction with treatment. Neurology
25. Stewart WF, Lipton RB, Dowson AJ, Sawyer J. Development and testing of the Migraine
Disability Assessment (MIDAS) Questionnaire to assess headache-related disability. Neurology
. 2001;56(6 suppl 1):S20–S28.
26. Buse DC, Dodick DW, Manack Adams A. Family Burden of Chronic Migraine
to the Migraineur: Results of the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study. Paper presented at: National Conference on Pain (PAINWeek); September 2-6, 2014; Las Vegas, NV, USA. Poster 13.
27. Buse DC, Fanning KM, Manack Adams A, Lipton RB. Migraine
Burden on Migraineurs and Their Spouses/Domestic Partners: Results From the Chronic Migraine
Epidemiology & Outcomes (CaMEO) Study. Paper presented at: 17th Congress of the International Headache Society (IHC); May 14-17, 2015; Valencia, Spain.
28. Lipton RB, Varon SF, Grosberg B, et al. OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine
29. Cole JC, Lin P, Rupnow MF. Validation of the Migraine
-Specific Quality of Life Questionnaire version 2.1 (MSQ v. 2.1) for patients undergoing prophylactic migraine
treatment. Qual Life Res
30. Martin BC, Pathak DS, Sharfman MI, et al. Validity and reliability of the migraine
-specific quality of life questionnaire (MSQ Version 2.1). Headache
31. Dodick DW, Lipton RB, Buse DC, et al. Effects of Demographic and Socioeconomic Characteristics on Barriers to Chronic Migraine
, and Treatment: Results From the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study (Poster 12). Paper presented at: National Conference on Pain (PAINWeek); September 2-6, 2014; Las Vegas, NV, USA.
32. Buse DC, Lipton RB, Reed ML, Serrano D, Fanning KM, Manack Adams A. Barriers to Chronic Migraine
Care: Results of the CaMEO (Chronic Migraine
Epidemiology & Outcomes) Study. Paper presented at: American Association of Nurse Practitioners Annual Meeting (AANP); June 17-22, 2014; Nashville, TN, USA.
33. Lanteri-Minet M. Economic burden and costs of chronic migraine
. Curr Pain Headache Rep
34. Munakata J, Hazard E, Serrano D, et al. Economic burden of transformed migraine
: results from the American Migraine
Prevalence and Prevention (AMPP) study. Headache
35. Dodick DW. Clinical practice. Chronic daily headache. N Engl J Med
36. Dougherty C, Silberstein SD. Providing care for patients with chronic migraine
, treatment, and management. Pain Pract
37. Loder E, Weizenbaum E, Frishberg B, Silberstein SAmerican Headache Society Choosing Wisely Task Force. Choosing wisely in headache medicine: the American Headache Society's list of five things physicians and patients should question. Headache
38. Lipton RB. Chronic migraine
, classification, differential diagnosis
, and epidemiology. Headache
. 2011;51(suppl 2):77–83.
39. Bigal ME, Lipton RB. The differential diagnosis
of chronic daily headaches: an algorithm-based approach. J Headache Pain
40. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine
in adults: The American Headache Society evidence assessment of migraine
41. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine
prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology
42. Diener HC, Dodick DW, Turkel CC, et al. Pooled analysis of the safety and tolerability of onabotulinumtoxinA in the treatment of chronic migraine
. Eur J Neurol
43. Aurora SK, Winner P, Freeman MC, et al.OnabotulinumtoxinA for treatment of chronic migraine
: pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011;51(9):1358–1373.
44. Blumenfeld A, Inocelda A, Purdy C, Dalfonso L, Magar R. The Durability of OnabotulinumtoxinA for the Treatment of Chronic Migraine
: CLARITY Pilot Study (Poster 9). Paper presented at: The National Conference on Pain (PAINWeek); September 2-6, 2014; Las Vegas, NV, USA.
45. Blumenfeld A, Silberstein SD, Dodick DW, Aurora SK, Turkel CC, Binder WJ. Method of injection of onabotulinumtoxinA for chronic migraine
: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache
46. Wells RE, Bertisch SM, Buettner C, Phillips RS, McCarthy EP. Complementary and alternative medicine use among adults with migraines/severe headaches. Headache
47. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine
prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology
48. Mauskop A. Nonmedication, alternative, and complementary treatments for migraine
. Continuum (Minneap Minn)
49. Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB. Transformed migraine
and medication overuse in a tertiary headache centre—clinical characteristics and treatment outcomes. Cephalalgia
50. Friedman BW, Hochberg ML, Esses D, et al. Recurrence of primary headache disorders after emergency department discharge: frequency and predictors of poor pain and functional outcomes. Ann Emerg Med
51. Radat F, Mekies C, Géraud G, et al. Anxiety, stress and coping behaviours in primary care migraine
patients: results of the SMILE study. Cephalalgia
52. Jensen R, Zeeberg P, Dehlendorff C, Olesen J. Predictors of outcome of the treatment programme in a multidisciplinary headache centre. Cephalalgia
53. Starling AJ, Dodick DW. Best practices for patients with chronic migraine
: burden, diagnosis
, and management in primary care. Mayo Clin Proc
54. Silberstein SD, Edvinsson L. Is CGRP a marker for chronic migraine