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Epidemiology and comorbidity of headache Rigmor Jensen, Lars J Stovner Lancet Neurol 2008; 7: 354–61 Danish Headache Center, Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark (R Jensen MD); and Norwegian National Headache Centre, Department of Neuroscience, Norwegian University of Science and Technology and St Olavs Hospital, Trondheim, Norway (LJ Stovner MD) Correspondence to: Rigmor Jensen, Danish Headache Center, University of Copenhagen, Glostrup Hospital, DK-2600 Glostrup, Denmark
[email protected]
The burden associated with headache is a major public health problem, the true magnitude of which has not been fully acknowledged until now. Globally, the percentage of the adult population with an active headache disorder is 47% for headache in general, 10% for migraine, 38% for tension-type headache, and 3% for chronic headache that lasts for more than 15 days per month. The large costs of headache to society, which are mostly indirect through loss of work time, have been reported. On the individual level, headaches cause disability, suffering, and loss of quality of life that is on a par with other chronic disorders. Most of the burden of headache is carried by a minority who have substantial and complicating comorbidities. Renewed recognition of the burden of headache and increased scientific interest have led to a better understanding of the risk factors and greater insight into the pathogenic mechanisms, which might lead to improved prevention strategies and the early identification of patients who are at risk.
Introduction Headache is the most prevalent neurological symptom1 and is experienced by almost everyone. Headache can be a symptom of a serious life-threatening disease, such as a brain tumour, but in most cases it is a benign disorder that comprises a primary headache such as migraine or tension-type headache (TTH).2 Nevertheless, migraine and TTH can cause substantial levels of disability, not only to patients and their families but also to society as a whole owing to its high prevalence in the general population.3–7 Unfortunately, the scope and scale of the burden of headache is underestimated, and headache disorders are universally under-recognized and undertreated. An important initiative, Lifting the Burden: The Global Campaign to Reduce the Burden of Headache, focuses on these widespread aspects of headache and is a collaboration between multinational health-care organisations and professionals to raise awareness of headache disorders in general.8 Another initiative, Cost of the Brain Disorders in Europe, includes migraine as a separate neurological disorder that ranks as number nine on the list of the most costly neurological disorders in both sexes, and as number three in women.1,6 TTH is the most common form of headache and is often thought of as a normal headache, in contrast to debilitating and characteristic migraine attacks or cluster headaches. Owing to its high prevalence, disability due to TTH is greater than that for migraine at the population level.3 Headache is among the ten most disabling disorders for both sexes and, if the burden of TTH is taken into account, among the five most disabling disorders for women, in accordance with the WHO’s ranking of the most disabling disorders.3 The main objectives of this Review are to present the recent epidemiological knowledge about primary headache disorders, their comorbidities, costs, risk factors, and prognoses.
Epidemiology Prevalence Although there are no biological markers for primary headaches such as migraine and TTH, their diagnosis is made with relatively high precision on the basis of the 354
diagnostic criteria of the second edition of the International Classification of Headache Disorders (ICHD-II),9 which were published in 2004 and are now applied worldwide. There might, however, be problems with case definitions in epidemiological studies, particularly the definition of TTH, which can greatly influence the prevalence rate; for example, problems can arise because the definition of TTH can overlap with probable migraine,10 and migraine is almost always comorbid with TTH. This might explain why the prevalence of TTH tends to vary more than the prevalence of migraine. Overall, the current global prevalence of headache is 47%, of migraine is 10%, of TTH is 38%, and of chronic headache is 3%.3 As expected, the lifetime prevalences are higher: 66% for headache, 14% for migraine, 46% for TTH, and 3·4% for chronic headache.3 The ICHD criteria can be used to summarise regional prevalences of headache disorders. Migraine is more prevalent in Europe and North America than it is in Africa (figure 1),3,7,10–37 whereas the prevalence of TTH seems to be much higher in Europe (80%) than it is in Asia and the Americas (20–30%). The frequency and duration of TTH varies considerably: from infrequent, short-lasting periods of discomfort to frequent, longlasting, or even continuous, disabling headaches. Therefore, pooling these extremes into an overall prevalence figure might be misleading. The lifetime prevalence of TTH was as high as 86% in a populationbased study in Denmark, but most of the patients (59%) had episodic infrequent TTH (1 day or less per month) without the need for medical attention.38 Nevertheless, 24–37% had TTH several times a month, 10% had TTH weekly, and 2–3% of the population had chronic TTH for most of their life.26,38,39 Data on chronic headache (lasting ≥15 days per month) are relatively scarce and therefore less reliable. In clinical practice, reports of chronic headache should always raise suspicion of a secondary headache due to neurological or systemic disease or frequent use of medication—socalled medication-overuse headache. Medication-overuse headache is a secondary chronic headache associated with more than 3 months’ overuse of analgesics (15 days http://neurology.thelancet.com Vol 7 April 2008
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IHS or modified IHS criteria Population or community based >500 participants Covering at least age groups 25–60 years
Figure 1: Studies on the 1-year migraine prevalence in adults3,7,10–37
or more intake per month) or more specific substances, such as triptans or ergotamine (≥10 days’ intake per month).9 The global prevalence of chronic headache is 3·4%, and it is most common in Central and South America (5%), and least common in Africa (1·7%).3,40–44 There are only a few large-scale epidemiological studies of cluster headache, and the lifetime prevalence in five European studies ranges from 0·06% to 0·3%.45–49 Whether regional differences are real or mainly a result of differences in the methodology of the various studies is uncertain. Many factors in addition to case definition influence the calculation of headache prevalence; these include the time frame of the headache, the method of data collection, the age and sex of the population, the participation rate, how the diagnostic criteria are applied, which diagnoses are considered, and, most importantly, how the screening questions are asked.50
Sex and age The male:female ratio for migraine among adults varies from 1:2 to 1:3, and women have more migraine without aura than migraine with aura.51,52 In prepubertal children, there is generally no sex difference.53 The male:female ratio for TTH is 4:5, indicating that, unlike for migraine, women are only slightly more affected than men.26,38,39 For both sexes, the prevalence of TTH peaks between the ages of 30 and 39 years, and the prevalence of http://neurology.thelancet.com Vol 7 April 2008
headache, in general, decreases with age. The prevalence of migraine increases with age until a peak is reached during the fourth decade of life; thereafter, the prevalence declines, with a more pronounced decline in women than in men.3,26,38,51,52 The most common age of onset of migraine is in the second and third decades of life (figure 2).26,52 The average age of onset of TTH is higher than for migraine, namely between 25 and 30 years in cross-sectional epidemiological studies,24,26,52 and TTH as well as other chronic headaches are probably lifelong disorders: prevalences tend to increase until the fifth decade, with only a minor decline with increasing age.
For more on the global campaign to lift the burden of headache worldwide see http:// www.liftingtheburden.org/
Incidence The incidence of developing migraine de novo has been estimated only rarely with uncertain results. In a Danish epidemiological follow-up study, the annual incidence of migraine was 8·1 per 1000 person years (male:female ratio 1:6) and 14.2 per 1000 person years for frequent TTH (male:female ratio 1:3).54 Both rates decreased with age. Risk factors for migraine include familial disposition, lack of secondary education, high work load, and frequent TTH. The risk factors for TTH include poor self-rated health, inability to relax after work, and sleeping for only a few hours per night. The incidence of migraine was higher than previously estimated from cross-sectional 355
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0 30) than in those who are normal weight.78 The area is further complicated because obesity is also a dependent risk factor for depression and anxiety. The association between depression and migraine is reported to be bidirectional: migraineurs have a fivefold higher risk of depression than the general population, and patients with depression have a threefold higher risk of migraine than the general population.87 There is a similar bidirectional association between anxiety and migraine. Taken together, the results of these studies support theories of a common neurobiology.88,89 However, when population-based data were adjusted for coexisting TTH, it was clear that TTH but not pure migraine was the main predictor for depression and anxiety.90 Therefore, in future long-term epidemiological studies, and in our work as headache doctors, it is important to identify comorbid disorders, including coexisting headache diagnoses, because the neurobiology, management, and outcome of headache are closely correlated with comorbidity.
Prognosis The results of a 40-year follow-up of 73 children with pronounced migraine showed that before the age of 25, http://neurology.thelancet.com Vol 7 April 2008
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23% of the patients did not have migraine, and women were significantly more likely to have migraine,91 but more than 50% still had migraine when they were around 50 years old. In a 12-year longitudinal epidemiological study from Denmark, 549 people participated in the follow-up study. Of 64 migraineurs at baseline, 42% were in remission, 38% had low-frequency migraine, and 20% had a poor outcome—more than 14 migraine days per year—at follow-up. Poor outcome was associated with a high frequency of migraine at baseline and an age of onset younger than 20 years,54 which accords with the results of a UK study on the prognosis of headache in general.92 Few studies have investigated the prognosis of patients with TTH. In the longitudinal study of the Danish population, 45% were in remission, 39% had unchanged frequent episodic TTH, and 16% had unchanged or newly developed chronic TTH at follow-up. Poor outcome was associated with chronic TTH at baseline, coexisting migraine, not being married, and sleeping problems.54 In a clinic-based 10-year follow-up study of 62 patients with episodic TTH, 75% continued to have episodic headache, whereas episodic TTH had developed into the chronic form in 25% of patients. In those patients with initial chronic TTH, at follow-up 31% were unchanged, 21% had developed medication-overuse headache, and the remainder had reverted to the episodic form, with or without prophylactic treatment.93 Depression, anxiety, and medication overuse were predictors of poor outcome in the clinical setting, and these patients might request increased medical attention in the future. Also, there are few clinical longitudinal reports for cluster headaches. In a 10-year Italian follow-up study, 13% of patients with an episodic form of cluster headache developed chronic cluster headache, whereas 33% of those with a chronic form developed the episodic form,94 and only 10% had no cluster headache during the past 3 years.94
Conclusions In conclusion, headache disorders are among the most prevalent, burdensome, and costly diseases in the world, and there is an urgent need for acceptance, education, and scientific interest. Most of the severely affected patients also have profound comorbid disorders, which complicate their overall management and outcome. Thus, the burden of headache on the patient, their families, and on society is considerable. Limited knowledge of the underlying pathophysiology combined with a lack of academic interest has previously resulted in the use of non-specific treatments, although management of migraine has improved and interest has increased during the past decade. Headache-related disability can be markedly reduced by increasing general awareness of headache, better education among health-care professionals, and the identification of trigger factors combined with http://neurology.thelancet.com Vol 7 April 2008
Search strategy and selection criteria References for this Review were identified by searches of MEDLINE between 1988 and September, 2007, and from the extensive files of the authors. The search terms “migraine”, “cluster headache”, “tension-type headache”, “daily headaches”, “epidemiology”, “comorbidity”, “prognosis”, and “burden of headache” were used. Abstracts from meetings were also included. Only papers published in English were included. The final reference list was compiled on the basis of originality, quality, use of the ICHD classification system, and relevance to the topic.
pharmacological management, although we still lack specific preventive modalities. Most importantly, early intervention, the identification of risk factors, and lifestyle associations might lead to effective strategies to prevent chronification of headache, which will have considerable benefits for the patient and the society. Contributors RJ made the initial plan and wrote the abstract, the introduction, and the sections about prevalence, incidence, and comorbidities. LJS participated in the planning of the Review, the literature list, and wrote the sections about cost and disability of headache. Conflicts of interest We have no conflicts of interest. References 1 Andlin-Sobocki P, Jönsson B, Wittchen HU, Olesen J. Cost of disorders of the brain in Europe. Eur J Neurol 2005; 12: 1–27. 2 Jensen R, Rasmussen BK. Burden of headache. Expert Rev Pharmacoeconomics Outcomes Res 2004; 4: 353–59. 3 Stovner L, Hagen K, Jensen R, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007; 27: 193–210. 4 Schwartz BS, Stewart WF, Simon D, Lipton RB. Epidemiology of tension-type headache. JAMA 1998; 279: 381–83. 5 Boardman HF, Thomas E, Croft PR, Millson DS. Epidemiology of headache in an English district. Cephalalgia 2003; 23: 129–37. 6 Olesen J, Leonardi M. The burden of brain diseases in Europe. Eur J Neurol 2003; 10: 471–77. 7 Morillo LE, Alarcon F, Aranaga N, et al. Prevalence of migraine in Latin America. Headache 2005; 45: 106–17. 8 Steiner TJ. Lifting the burden: the global campaign against headache. Lancet Neurol 2004; 3: 204–05. 9 The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004; 24 (suppl 1): 9–160. 10 O’Brien B, Goeree R, Streiner D. Prevalence of migraine headache in Canada: a population-based survey. Int J Epidemiol 1994; 23: 1020–26. 11 Schwartz BS, Stewart WF, Lipton RB. Lost workdays and decreased work effectiveness associated with headache in the workplace. J Occup Environ Med 1997; 39: 320–27. 12 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 2001; 41: 646–57. 13 Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology 2002; 58: 885–94. 14 Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA 1992; 267: 64–69. 15 Stewart WF, Lipton RB, Liberman J. Variation in migraine prevalence by race. Neurology 1996; 47: 52–59. 16 Kryst S, Scherl E. A population-based survey of the social and personal impact of headache. Headache 1994; 34: 344–50.
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