Editorial

Cephalalgia 0(0) 16 ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102413477736 cep.sagepub.com

Global perspectives on the burden of episodic and chronic migraine

Dawn C Buse1,2 and Richard B Lipton1,2

Recent studies have proled chronic migraine (CM) and episodic migraine (EM) in many regions of the world using samples derived from various sources. In a previous issue of Cephalalgia, Wang and colleagues contrast patients with CM and EM recruited from two headache clinics in Taiwan (1). Their results add to the growing evidence indicating that, in comparison with EM, CM is less common but far more burdensome to individuals, as evidenced by measures of headacherelated disability, medical and psychiatric comorbidities, and health-related quality of life (HRQoL), and to society, as indexed by measures of lost productive time as well as direct medical costs. In 2011, the World Health Organization and Lifting the Burden Campaign against Headache published the Atlas of Headache Disorders and Resources in the World 2011. The authors of The Atlas stated, Our view of the global burden attributable to headache disorders is incomplete. . . (2). They urged researchers around the world to gather and publish data on the prevalence, burden, and other variables related to primary headaches in order to increase the understanding of the global status of headache prevalence, burden, costs, and care. They estimated the prevalence of headache on 15 days per month (an approximation of chronic daily headache (CDH)) in Southeast Asia to be 1.7% based on a compilation of data from epidemiological studies. CM is a form of CDH; however, The Atlas did not report rates of CM. In their recent systematic review of CDH and CM in the Asia-Pacic region, Stark and colleagues (3) identied two population studies, both from Taiwan, that reported the prevalence of CM as 1.7% (reported as transformed migraine (TM)) (4) and 1.0% (reported as CDH with migrainous features) (5). They also identied 19 clinic-based studies that reported rates and features of patients with CM. They concluded that Asia may have a lower prevalence of CM and CDH than the international average, although the rates of CM reported in the studies from Taiwan are similar

to the prevalence of CM reported by the American Migraine Prevalence and Prevention (AMPP) study (6). Stark et al. also noted that CM was associated with signicant headache-related disability, functional impairment, and psychiatric comorbidity in reports of clinic studies from Taiwan, Korea, and China. These ndings from the Asia-Pacic region are similar to those reported by large international (7,8), North American (6), and European studies (9), which have also demonstrated that CM is associated with greater disease burden on multiple indices compared with EM. Making comparisons among studies and variations regions of the world is dicult because of variation in sources of study subjects and data collection methods among other factors. Fortunately, the AMPP study, the International Burden of Migraine Study (IBMS), and the study by Wang and colleagues collected and reported similar data, which allows for comparisons across studies. The AMPP study screened 120,000 United States (US) households selected to be representative of the US population and had a 64.9% response rate. Of 28,261 respondents who reported experiencing severe headache in the preceding year, 24,000 were followed annually from 2005 to 2009 with mailed, written questionnaires. The AMPP survey instrument was based on validated items from the American Migraine Studies 1 and 2 (10,11) along with validated questionnaires such as the Migraine Disability Assessment Scale (MIDAS) (12). The IBMS utilized a targeted, Webbased methodology to recruit and survey participants with EM and CM in 10 countries. Invitations were sent via email to 72,059 panelists. Of 23,312 respondents
1 2

Albert Einstein College of Medicine, NY, USA Montefiore Headache Center, NY, USA

Corresponding author: Dawn C Buse, Albert Einstein College of Medicine of Yeshiva University, Montefiore Headache Center, 1575 Blondell Ave., Suite 225, Bronx, NY 10461, USA. Email: dbuse@montefiore.org

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(32.4% response rate), 555 participants with CM and 9160 with EM were eligible and completed the Phase I and Phase 2 surveys (41.7%). The IBMS survey was largely composed of items and instruments from the AMPP study surveys with additional validated instruments added and translated into multiple languages. Though Taiwan was one of the 10 countries surveyed in the IBMS study, the recruited sample was too small for meaningful analysis. Wang and colleagues aimed to gather data from individuals with EM and CM from headache clinics in Taiwan to ll this gap in knowledge. Wang and colleagues based their survey on the IBMS, with the addition of physician interviews for diagnosis and translation into Taiwanese. In the current study, Wang and colleagues recruited 331 patients with migraine (164 with EM and 167 with CM) from two headache clinics in Taiwan. Diagnosis of EM or CM was made by physicians using Silberstein-Lipton criteria (13,14). Participants completed a questionnaire comprised of items on sociodemographics, headache-related disability, quality of life, medical and psychiatric comorbidities, lost productivity, and healthcare resource utilization, among other topics. The authors found that compared with participants with EM, participants with CM had signicantly higher headache-related disability, more medical and psychiatric comorbidities including higher scores on a standardized depression and anxiety screening instrument (Patient Health Questionnaire-4 (PHQ-4)), greater likelihood of endorsing a history of a range of medical and psychiatric comorbidities, increased healthcare resource utilization, and greater work productivity loss. These results are compatible with results seen in the AMPP and IBMS (68,1519). In addition, participants with CM had worse health status scores and reduced HRQoL, ndings that are comparable to those observed in the IBMS (7,8). Although Wang et al., the IBMS, and the AMPP all demonstrated that people with CM have signicantly greater headache-related disability than individuals with EM, determined by the MIDAS, there were dierences among the studies (see the Table 1). Based on the assumption that patients within a clinic generally have more severe disease than individuals within the population, it is not surprising that headache-related disability (MIDAS score/grade) was higher for individuals with CM and EM from the Taiwanese clinic sample than in the US population sample. Among participants with CM, 41.3% of those from Wang et al. had very severe headache-related disability (MIDAS Grade IV-B) (7) compared with 24.8% of those in the AMPP study. Similarly, 7.9% of those with EM from the Wang et al. study and 3.2% of those from the AMPP study had scores in the MIDAS Grade IV-B category. Although the absolute rates of very severe headache-related

Cephalalgia 0(0) disability diered across studies, the proportions of very severe headache-related disability within each sample (comparing the CM to the EM group within a study) were fairly similar. In the Wang et al. manuscript, patients with CM were 5.2 times more likely to have very severe headache-related disability than participants with EM. In the AMPP study, participants with CM were 7.8 times more likely to have very severe headache-related disability than participants with EM. Levels of headache-related disability were highest in the IBMS. Higher levels of disability in the IBMS compared with the AMPP study are not surprising owing to possible eects of the targeted recruitment strategy, which likely led to a greater participation of participants with more severe disease in the IBMS. However, higher rates of disability in the IBMS than in Wang et al. are surprising as the Taiwanese sample was derived from a specialty-care setting where increased disability is likely. Interestingly, when comparing disability per headache day (MIDAS sum score for three months/number of headache days in three months), participants from the Asian sample reported less lost productive time than those in the IBMS (Wang et al. sample: CM 0.70 lost day per headache day, EM sample 1.04 lost days per headache day) compared with those from the IBMS (CM 1.13 lost days per headache day, EM 1.39 lost days per headache day). Within both studies, participants with CM reported less lost productive time in days than participants with EM per headache. The nding that participants in the Wang et al. study had less lost productive time in days per headache may reect a reduced burden of CM and EM in Asian populations, a cultural dierence in symptom reporting or illness behavior, the benets of treatment provided in headache centers, selective participation in the IBMS, or a combination of factors. A comparison of similarities and dierences of these three studies of persons with EM and CM raises interesting questions. It is dicult to disentangle three possible inuences: 1. race, 2. reporting and 3. the source of the sample. Variation between the three samples may reect genuine epidemiological dierences based on factors such as race-related genetic dierences, social norms, healthcare access, diet, and symptom reporting. Dierences between the Asian and Western populations could arise because of genetic dierences in pain expression or illness severity. A US study found that the prevalence of migraine in Asian-Americans was 5060% that of Caucasians (20). Some research has also identied race or ethnic dierences in pain perception and response, although dierences in physiological pain thresholds have not been consistently replicated (21). Dierences could also arise because of cultural dierences in symptom reporting,

Table 1. Selected data from Wang et al., IBMS and AMPP study. Wang et al. study CM EM CM EM CM EM International Burden of Illness Study (IBMS) American Migraine Prevalence and Prevention (AMPP) study

Buse and Lipton

Variable

Sociodemographics and headache frequency1,2 Average age (years) % Female % Obese (BMI 30) % Employed full time % Married % Completed bachelors degree and higher Income 42.2 76.6% 3.0% 52.7% 60.5% 38.9% NT$1,300,001 (approx. $43,333 US) 8.4% 22.0 64.4 10.4 40.3 78.7% 4.3% 64.0% 64.6% 45.1% NT$1,300,001 (approx. $43,333 US) 9.8% 4.6 41.2 87.4% 24.3% 35.5% 49.9% 28.0% >Median county income 28.5% 39.7 81.3% 19.4% 49.3% 46.8% 34.5% >Median county income 31.9% 47.7 78.6% 25.5% 37.8% 59.3% 28.2% Income $60,000/ yr 32.6%

46.0 80.0% 21.0% 52.3% 60.8% 31.7% Income $60,000/ yr 36.3%

46.1 41.3% 21.6% 46.1/66.0 0.70 7.9% 43.9% 14.4/13.8 1.04

14.4

72.6 63.5% 6.8% 72.6/64.4 1.13

14.5 6.3% 30.7% 14.5/10.4 1.39

24.8% 42.7%

3.2% 65.1%

Days in the last month with headache of any intensity Days in the last three months with headache of any intensity1 Headache-related disability3,4 Average MIDAS sum score (headache-related disability) % MIDAS Grade IVB (very severe) % MIDAS Grade I (none or minimal) Lost productive time per day with headache (MIDAS score/ number of headache days in past three months)6 Quality of life3,5 MS-QOL- RFR MS-QOL- REP MS-QOL_ EF Comorbidities1,2 Number of comorbid conditions SR-PD pain comorbidities (group) SR-PD cardiovascular disease risk factors (group) SR-PD cardiovascular disease events (group) SR-PD psychiatric disorders (group) 56.4 70.1 62.0 70.8 81.4 78.1 61.4 44.4 48.3 71.7 56.5 67.2 40.7% 29.9% 13.2% 43.1% 20.1% 22.0% 5.5% 24.4% 2.1 38.0% 41.6% 8.5% 45.6%

1.7 18.2% 33.7% 3.5% 29.7%

3
(continued)

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NT: New Taiwan dollars. Exchange rate as of August 2012 was approximately $1 US 30 NT dollars; SR-PD: respondent self-report of ever receiving a physician diagnosis of a given condition; CM: chronic migraine; EM: episodic migraine; BMI: body mass index; 1IBMS data from Payne et al., 2011; 2AMPP data from 2005 AMPP survey, Buse et al., 2010; 3IBMS data from Blumenfeld et al., 2011; 4AMPP data from 2004 AMPP survey, Buse et al., 2012; 5Quality of life data was assessed with the Migraine Specific Quality of Life instrument, version 2.1 (MSQ v2.1). RFP: role functioning preventive; RFR: role functioning restrictive; EF: emotional functioning. Higher scores indicate better quality of life; lower scores indicate worse quality of life; 6Estimated from Wang et al. by multiplying number of days in past month by three. MIDAS: Migraine Disability Assessment Scale; PHQ-4: Patient Health Questionnaire.

Cephalalgia 0(0) though that is very dicult to examine without specifically designed studies. Dierences may also be due to the sources of the samples. In general, patients who seek specialty medical care have more severe disease than those in the general population (22). Interestingly, this was not the case in terms of comorbidities, where 38.0% of those with CM in the IBMS study and 40.7% of those in the Wang et al. study reported one or more pain conditions (other than headache), and 45.6% of those with CM in IBMS and 43.1% of those with CM in Wang et al. reported being diagnosed with depression or anxiety by a physician. These ndings are in line with a recent Brazilian study that found similar rates of depression between people with CM from a clinic (n 43) and those sampled from the community (n 41) (23). Using a structured clinical interview, psychiatrists found that 39.3% of patients with CM in a tertiary-care setting and 32.6% of residents in a city borough met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for depression. The study by Wang and colleagues is an important addition to the scientic literature. It oers valuable data from Taiwan, expands our perspective on patterns of disease severity, disability, and comorbidity of CM and EM, and allows for comparisons with studies with similar variables and instruments. Comparisons across cultures and regions of the world are challenging because of possible dierences in illness biology, culture and treatment. However, the use of similar items and instruments between the AMPP study, the IBMS and the present report by Wang et al. facilitates comparisons across samples of dierent types (clinic vs. population) and among dierent regions of the world. In this review, we nd that patients with CM and EM in Wang et al. had greater headache-related disability than seen in the population-based AMPP study. However, disability and comorbidity rates were higher in the IBMS than in Wang et al. Wang and colleagues also report data on health resource utilization, quality of life, medical and psychiatric conditions, and other important indices of disease severity and burden. Broadly, the results show that EM and CM are both disabling and both disrupt quality of life and are associated with medical and psychiatric comorbidities, yet the burden is consistently greater among those with CM. Based on this study, the studies summarized in the Table and on an expanding body of literature, we conclude that the burden of CM greatly exceeds that of EM in North America, Europe, and Asia, particularly Taiwan. In comparison to people with EM, those with CM have greater individual burdens, as measured by lost time due to headache, unemployment, and underemployment as well as

American Migraine Prevalence and Prevention (AMPP) study

10.6% 13.9% 9.0% 6.6%

International Burden of Illness Study (IBMS)

26.5% 20.4% 16.9% 21.2%

18.9% 9.8% 1.8% 1.3%

Wang et al. study

38.3% 19.8% 7.2% 17.4%

SR-PD chronic pain SR-PD high blood pressure SR-PD arthritis PHQ-4 (depression anxiety) severe3

Table 1. Continued.

SR-PD depression SR-PD anxiety

Variable

28.7% 32.3%

CM

6.7% 20.7%

EM

33.7% 34.2%

CM

17.8% 21.7%

EM

31.5% 33.7% 33.6% Depression with PHQ9 30.2% 41.2% 30.2%

CM

15.1% 25.6% 22.2% Depression with PHQ9 17.2% 25.6% 18.8%

EM

Buse and Lipton reduced HRQoL. They also produce a greater societal burden, as measured by direct and indirect medical costs. Future work should continue to gather data on the burden, comorbidities, and direct and indirect costs of EM and CM in geographic regions around the world in a variety of settings to continue to expand our knowledge and understanding of migraine.

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6. Buse DC, Manack AN, Fanning K, et al. Chronic migraine prevalence, disability, and sociodemographic factors: Results from the American Migraine Prevalence and Prevention Study. Headache. Epub ahead of print 22 June 2012. DOI: 10.1111/j.1526-4610.2012.02223.x. 7. 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 2011; 31: 301315. 8. Payne KA, Varon SP, Kawata AK, et al. The International Burden of Migraine Study (IBMS): Study design, methodology, and baseline cohort characteristics. Cephalalgia 2011; 31: 11161130. 9. Katsarava Z, Yoon M-S, Obermann M, et al. Prevalence and sociodemographic differences between episodic and chronic migraine: Respondents in a GHC study. European Headache and Migraine Trust International Congress, London, UK, 47 September 2008. 10. Lipton RB, Stewart WF and Simon D. Medical consultation for migraine: Results from the American Migraine Study. Headache 1998; 38: 8796. 11. Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: Data from the American Migraine Study II. Headache 2001; 41: 646657. 12. Stewart WF, Lipton RB, Kolodner K, et al. Reliability of the migraine disability assessment score in a populationbased sample of headache sufferers. Cephalalgia 1999; 19: 107114. 13. Silberstein SD, Lipton RB, Solomon S, et al. Classification of daily and near-daily headaches in the headache clinic. Proposed revisions to the International Headache Society criteria. In: Olesen J (ed.) Frontiers in headache research. New York: Raven Press Ltd, 1994, pp.117126. 14. Silberstein SD, Lipton RB and Sliwinski M. Classification of daily and near-daily headaches: Field trial of revised IHS criteria. Neurology 1996; 47: 871875. 15. Buse DC, Manack A, Serrano D, et al. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry 2010; 81: 428432. 16. Buse DC, Manack AN, Serrano D, et al. Headache impact of chronic and episodic migraine: Results from the American Migraine Prevalence and Prevention study. Headache 2012; 52: 317. 17. Stewart WF, Bruce C, Manack A, et al. A case study for calculating employer costs for lost productive time in episodic migraine and chronic migraine: Results of the American Migraine Prevalence and Prevention Study. J Occup Environ Med 2011; 53: 11611171. 18. Stewart WF, Wood GC, Manack A, et al. Employment and work impact of chronic migraine and episodic migraine. J Occup Environ Med 2010; 52: 814. 19. Stokes MS, Werner JB, Lipton RB, et al. Cost of health care among patients with chronic migraine and episodic migraine in Canada and the USA: Results from the International Burden of Migraine Study (IBMS). Headache 2011; 51: 10581077.

Funding
This research received no specic grant from any funding agency in the public, commercial, or not-for-prot sectors.

Conflicts of interest
Dawn C. Buse, PhD, has received honoraria and/or research funding from Allergan Pharmaceuticals, Merck Inc, MAP Pharmaceuticals, NuPathe, and Novartis. Richard B. Lipton, MD, has received research support from the National Institutes of Health (NIH) (PO1 AG03949 (program director), PO1AG027734 (project leader), RO1AG025119 (investigator), RO1AG022374-06A2 (investigator), RO1AG034119 (investigator), RO1AG12101 (investigator), K23AG030857 (mentor), and K23NS051 40901A1 (mentor), and K23NS47256 (mentor)); the National Headache Foundation and the Migraine Research Fund; serves on the editorial board of Neurology; has reviewed for the National Institute on Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS); holds stock options in eNeura Therapeutics (a company without commercial products in the US); and serves as consultant, advisory board member, or has received honoraria from: Allergan, American Headache Society, Autonomic Technologies, Boston Scientic, Bristol Myers Squibb, CogniMed, Colucid, Eli Lilly, Endo, eNeura Therapeutics, GlaxoSmithKline, MAP, Merck, Nautilus Neuroscience, Novartis, NuPathe, and Pzer.

References
1. Wang SJ, Wang PJ, Fuh JL, et al. Comparisons of disability, quality of life, and resource use between chronic and episodic migraineurs: A clinic-based study in Taiwan. Cephalalgia 2013; 33(3): 171181. 2. World Health Organization and Lifting the Burden Campaign Against Headache. Atlas of headache disorders and resources in the world 2011. Geneva: WHO, 2011. 3. Stark RJ, Ravishankar K, Siow HC, et al. Chronic migraine and chronic daily headache in the Asia-Pacific region: A systematic review. Cephalalgia. 2013; 33(4): 266283. 4. Lu SR, Fuh JL, Chen WT, et al. Chronic daily headache in Taipei, Taiwan: Prevalence, follow-up and outcome predictors. Cephalalgia 2001; 21: 980986. 5. Wang SJ, Fuh JL, Lu SR, et al. Chronic daily headache in Chinese elderly: Prevalence, risk factors, and biannual follow-up. Neurology 2000; 54: 314319.

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20. Stewart WF, Lipton RB and Liberman J. Variation in migraine prevalence by race. Neurology 1996; 47: 5259. 21. Alabas OA, Tashani OA and Johnson MI. Effects of ethnicity and gender role expectations of pain on experimental pain: A cross-cultural study. Eur J Pain. Epub ahead of print 16 October 2012. DOI: 10.1002/j.15322149.2012.00229.x.

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