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Epidemiology and comorbidity of headache

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 Review
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
rigj@glo.regionh.dk
354
Epidemiology and comorbidity of headache
Rigmor Jensen, Lars J Stovner
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 diagnostic criteria of the second edition of the
Headache is the most prevalent neurological symptom1 International Classification of Headache Disorders
and is experienced by almost everyone. Headache can be (ICHD-II),9 which were published in 2004 and are now
a symptom of a serious life-threatening disease, such as a applied worldwide. There might, however, be problems
brain tumour, but in most cases it is a benign disorder with case definitions in epidemiological studies,
that comprises a primary headache such as migraine or particularly the definition of TTH, which can greatly
tension-type headache (TTH).2 Nevertheless, migraine influence the prevalence rate; for example, problems can
and TTH can cause substantial levels of disability, not arise because the definition of TTH can overlap with
only to patients and their families but also to society as a probable migraine,10 and migraine is almost always
whole owing to its high prevalence in the general comorbid with TTH. This might explain why the
population.3–7 prevalence of TTH tends to vary more than the prevalence
Unfortunately, the scope and scale of the burden of of migraine.
headache is underestimated, and headache disorders are Overall, the current global prevalence of headache is
universally under-recognized and undertreated. An 47%, of migraine is 10%, of TTH is 38%, and of chronic
important initiative, Lifting the Burden: The Global headache is 3%.3 As expected, the lifetime prevalences
Campaign to Reduce the Burden of Headache, focuses on are higher: 66% for headache, 14% for migraine, 46% for
these widespread aspects of headache and is a collaboration TTH, and 3·4% for chronic headache.3
between multinational health-care organisations and The ICHD criteria can be used to summarise regional
professionals to raise awareness of headache disorders in prevalences of headache disorders. Migraine is more
general.8 Another initiative, Cost of the Brain Disorders in prevalent in Europe and North America than it is in
Europe, includes migraine as a separate neurological Africa (figure 1),3,7,10–37 whereas the prevalence of TTH
disorder that ranks as number nine on the list of the most seems to be much higher in Europe (80%) than it is in
costly neurological disorders in both sexes, and as number Asia and the Americas (20–30%). The frequency and
three in women.1,6 TTH is the most common form of duration of TTH varies considerably: from infrequent,
headache and is often thought of as a normal headache, short-lasting periods of discomfort to frequent, long-
in contrast to debilitating and characteristic migraine lasting, or even continuous, disabling headaches.
attacks or cluster headaches. Owing to its high prevalence, Therefore, pooling these extremes into an overall
disability due to TTH is greater than that for migraine at prevalence figure might be misleading. The lifetime
the population level.3 Headache is among the ten most prevalence of TTH was as high as 86% in a population-
disabling disorders for both sexes and, if the burden of based study in Denmark, but most of the patients (59%)
TTH is taken into account, among the five most disabling had episodic infrequent TTH (1 day or less per month)
disorders for women, in accordance with the WHO’s without the need for medical attention.38 Nevertheless,
ranking of the most disabling disorders.3 24–37% had TTH several times a month, 10% had TTH
The main objectives of this Review are to present the weekly, and 2–3% of the population had chronic TTH for
recent epidemiological knowledge about primary most of their life.26,38,39
headache disorders, their comorbidities, costs, risk Data on chronic headache (lasting ≥15 days per month)
factors, and prognoses. are relatively scarce and therefore less reliable. In clinical
practice, reports of chronic headache should always raise
Epidemiology suspicion of a secondary headache due to neurological or
Prevalence systemic disease or frequent use of medication—so-
Although there are no biological markers for primary called medication-overuse headache. Medication-overuse
headaches such as migraine and TTH, their diagnosis is headache is a secondary chronic headache associated
made with relatively high precision on the basis of the with more than 3 months’ overuse of analgesics (15 days
http://neurology.thelancet.com Vol 7 April 2008
 Review

13·223
11·622

10·026
14·710
13·311 23·221 10·237
11·714 22·335
9·628 8·436
12·212
14·325
5·934
14·015
16·727
24·624

11·613 8·516 7·733

8·5
7
10·129
10·07 9·032
13·519
12·6 7
3·0
30

9·37
16·317 5·031
8·27

5·318

7·320 5·07

Africa 4·0 (2 studies) Europe 14·8 (9 studies) • IHS or modified IHS criteria
Asia 10·6 (6 studies) North America 11·1 (7 studies) • Population or community based
Australia South America 9·6 (10 studies) • >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
For more on the global
campaign to lift the burden of
headache worldwide see http://
headache, in general, decreases with age. The prevalence www.liftingtheburden.org/
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.
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

http://neurology.thelancet.com Vol 7 April 2008 355

 Review
30
Women
25 Men
Migraine prevalence (%)
20
15
10
5 migraine cost studies have been done there were large
0 differences in methodology and the data available.59 All the
<10 10–19 20–29 30–39 40–49 50–59 60–69 70–79
Age (years)
Figure 2: Migraine prevalence in relation to age in men and women in Europe
Reproduced with permission from Blackwell Publishing.50
studies. The sex difference in patients with TTH differed
from migraine and no association with educational level
was observed.54 There are only few data on the incidence
of cluster headache, and this varies betweeen 2·5 per
100 000 person years in an Italian study45 and 9·8 per
100 000 person years in a US study.55 The peak incidence
in men was between the ages of 40 and 49 years and in
women between 60 and 69 years.55 Intriguing data from
the USA indicate that the incidence might be decreasing,
but the case-finding method and the case definitions of
this study are unconventional, and the results need to be
confirmed.56
Costs and disability
Costs
The total economic burden of migraine has been
estimated in the USA57 and Europe58 on the basis of
population-based prevalence studies, which reported a
prevalence of about 14% in both regions. The two studies
used different types of data sources for the cost estimates,
although the results of both clearly show that most of the
cost of migraine can be attributed to indirect costs, such
as absence from work or reduced efficiency when working
with headache. The US study,57 which used cost data from
1994, estimated the total cost of 22 million migraineurs
aged between 20 and 65 years to be $14·4 billion. The
direct costs (eg, medication, consultations, investigations,
and hospitalisation) accounted for only $1 billion,
whereas the indirect costs were estimated at $13.3 billion.
Woman incurred about 80% of both the direct and the
indirect costs of migraine. An important conclusion of
the study was that the burden of migraine disproportionally
falls on the patients and their employers.57
The European estimate was published in a report on the
cost of all brain disorders in the 25 EU countries at the
time plus Iceland, Norway, and Switzerland.58 The basis of
356
the estimate was a review of the available migraine cost
studies in Europe59 combined with a review of the
epidemiological evidence50 corrected for comorbidity and
differences in purchasing power of the different countries.58
The total estimated cost of migraine was €579 per patient,
or €27 billion for the 41 million patients aged between 18
and 65 years;1 almost 90% were indirect costs.58,59 Migraine
was by far the most prevalent of all the purely neurological
disorders, and although it had the lowest cost per patient it
was more costly than other neurological disorders, such as
stroke, multiple sclerosis, Parkinson’s disease, and
dementia.1 However, in the different countries where
variations in the cost estimates, most probably owing to
European studies were done before or soon after the
triptans were available; therefore, the high cost of this
group of drugs was not taken into account.
Relatively little is known about the cost of TTH. The
results of two Danish studies have shown that the
number of work days missed in the population owing to
TTH was three times higher than the number for
migraine;60,61 and a US study has also found that
absenteeism due to TTH is considerable.34 The indirect
costs of all headaches are several times higher than the
costs for migraine alone, which suggests that the costs of
non-migrainous headaches (mainly TTH) are higher
than those for migraine.29 Under the assumption that the
indirect costs of TTH far outweigh the direct costs, we
can speculate that the cost of TTH is greater than the cost
of migraine.3,11,58,62 However, proper studies on the cost of
TTH are urgently needed to appraise the real burden of
headache.
The direct costs due to medical services and medications
are 54% higher for TTH than for migraine because of the
higher prevalence of TTH and because the probability of
consulting a physician is higher in the many younger
patients who have TTH.58,60–61 Owing to the lack of a
specific and effective treatment for TTH, patients usually
consult many doctors and spend large sums of money on
so-called alternative treatments but have to live most of
their lives without effective pain relief for the headaches.
The burden of cluster headache has been studied in a
series of 78 consecutive patients from The Danish
Headache Center and compared with the use of health-
care services in the general population:63 all patients had
consulted their GP; 43·5% had seen specialists; 10·6%
had required emergency services; and 1·2% had been
admitted to hospitals. The indirect costs were also
substantial: 29·6% of the gainfully employed patients
with cluster headache had been absent from work
compared with the headache-related absence rate of
12·3% in the general population.63
Disability
The US Migraine Cost Study calculated that migraine
was the cause of 112 million bedridden days per year,
http://neurology.thelancet.com Vol 7 April 2008
 Review

which corresponds to 300 000 people staying in bed

30 Global
every 24 hours because of headaches.57 In population- Asia
based studies from Sweden, patients with migraine Europe
have also reported impairment between attacks,64 and North America
25
South and Central America
9% have stated that they do not recover completely from
attacks.65
Disability-adjusted life years—a measure of disease 20

Burden of headache
burden used by the WHO—is the sum of the years of life
lost and the years lived with disability.66 Although 15
migraine entails no increased mortality (ie, years of life
lost=0), it was ranked 19th in the leading global causes of
disability-adjusted life years among women aged 15–44; 10
with regard to years lived with disability, migraine was
ranked 19th for both sexes and 12th for women,
5
irrespective of age.6 By use of the WHO data to calculate
the burden of brain disorders (ie, psychiatric and
neurological disorders) in Europe, the overall burden of 0
migraine was lower than the seperate burdens of the Migraine Tension-type headache Total
major psychiatric disorders, dementias, stroke, and
injuries, but higher than the burden of epilepsy, multiple Figure 3: The burden of headache
sclerosis, and Parkinson’s disease, respectively.6,66 The burden of headache is calculated as headache days per year per person in the population multiplied by the
average intensity of headache. Reproduced with permission from Blackwell Publishing.3
The results of a Swedish study show that 27% of
patients have 70% of the migraine attacks, and thereby
carry most of the burden.64 This calculation has been
replicated through the application of the Migraine Sex life 7 8 28 Highly negative influence
Negative influence
Disability Assessment Scale.66,67,68 In France, 22% of Some negative influence
Love life 3 6 22
patients with active migraine, who correspond to 1·5%
of the whole population, had a Migraine Disability Finding
12 8
friends
Assessment Scale score of three or four, which indicates
Social
11 days or more absence from work during a 3-month position
3 10 24
period, a 50% or more reduction in productivity (job or
household chores), or an inability to participate in social Leisure time 8 14 37

activities.68 In the USA69 and England,70 the proportion

Finances 4 6 20
of patients with migraine who had a Migraine Disability
Assessment Scale score of three or four was more than Family
6 23 38
situation
50%.
Although Migraine Disability Assessment Scale score Studying 9 12 27
data are available for only a few countries, a recent review3 Work
of the global prevalence and burden of headaches has 11 18 47
attendance
tried to estimate the burden by the use of data on Career
3 8 16
migraine prevalence, attack frequency, and intensity. The progression
migraine burden was relatively similar for the four 0 20 40 60 80
continents that had sufficient data (Europe, Asia, North Percentage of migraineurs
America, South and Central America; figure 3).3 The
results of the study also showed that the burden of TTH Figure 4: Effect of migraine on important aspects of life
was greater than the burden of migraine, which is Reproduced with permission from Blackwell Publishing.65
supported by the finding that absence from work owing
to TTH is much greater than absence from work owing in patients with moderate or severe migraine,70 and a
to migraine.60 study from the Netherlands found that the negative
Some studies have measured quality of life with the influence of migraine was larger than the negative
SF-36 questionnaire, which enables migraine to be influence of disorders such as asthma.71 Comorbidities,
compared with other chronic disorders and eight quality such as depression, add to the reduction in the quality
of life measures. One US study69 that recruited patients of life of migraineurs,72 and the lower quality of life
with migraine from a medication trial found that remains after adjustments for socioeconomic status and
migraineurs had a lower quality of life than the general depression.72
US population. The authors of a population-based study The negative effect of migraine on family life has been
in the UK reported lower quality of life on all measures assessed in studies from Sweden, the UK, and the USA.

http://neurology.thelancet.com Vol 7 April 2008 357

 Review
In Sweden, migraine affected family, love life, and sex
life almost as much as it affected work (figure 4).65 The
US and UK studies69,70 also found considerable effects on
the partners of patients with migraine: 24% of partners
missed days of family or social activities, and 12% avoided
making plans for family or social activities owing to the
proband’s migraine. The patients with migraine also
reported that the disease considerably influenced their
ability to be a good parent, and a minority (0·4%) stated
that they avoided having children because of their
migraine.
The effects of TTH on the individual include physical
suffering, loss of quality of life, and economic effects, but
these are difficult to quantify. Chronic TTH had a
profound negative effect on the emotional life of the
affected patients because they were seven times more
likely to be classified as impaired on all subscales of the
applied quality of life surveys than were the controls,
which is similar or worse than for patients with a well
accepted diagnosis of chronic pain.73 Specific measures
of disability and quality of life in patients with TTH have
not been developed.
With regard to cluster headache, 78% of patients
reported restrictions in daily living, and 13% of patients
reported inhibition outside cluster periods. Major
decreases in the ability to participate in social activities,
family life, and housework were reported by 25% of
patients with TTH. The disease led to lifestyle changes in
96% of patients, most commonly in sleeping habits and
avoidance of alcohol.63
Comorbidity
Comorbidity is defined as a medical condition that exists
simultaneously but independently with another
condition, although recent descriptions have questioned
this and have implied causality between certain comorbid
disorders.74
The study of the co-occurrence of highly prevalent
disorders such as TTH and migraine with other disorders
requires careful statistical analysis before any clear
conclusions about causality can be made. Several
headache disorders can occur within the same individual
(ICHD-II), and patients can have up to five different
ICHD-II diagnoses.75,76 In the general population, 94% of
migraineurs have TTH, and 56% of these have frequent
episodic TTH.38 By contrast, TTH occurs with similar
prevalence in patients with and without migraine, which
leads to the assumption that migraine can trigger TTH,
whereas TTH might not trigger migraine.38 The prevalent
secondary headache and potentially preventable
medication-overuse headache occur, by definition, most
frequently in patients with primary headaches and are
closely linked by a common, as yet, unknown
neurobiological denominator.77
In general, headache disorders, and particularly
migraine, have been linked to various illnesses, including
well defined disorders, such as stroke, hypertension,
358
diabetes, asthma, and obesity,78,79 and some less well
defined disorders, such as fibromyalgia, lower back pain
or local muscle pain,80 anxiety, and depression.81,82
Migraine, hypertension, and obesity are all independent
risk factors for cardiovascular diseases, particularly
stroke, and the relative risk of stroke is 2·27–8·7 in
women with migraine with aura who are younger than
45 years, and 1·83 in women with migraine without aura.
The risks increase significantly when migraine with aura
is associated with smoking or the use of oral
contraceptives.83,84 Similarly, there is an increased risk of
stroke in women with migraine with aura (odds ratio
[OR] 2·25), but not with migraine without aura, who are
between the ages of 45 and 55 years, although this risk
was not seen in older women.84 Isolated hypertension
was unrelated to migraine; rather, it was inversely related
to non-migrainous headache in a large Norwegian
population study.85 In the same population, diabetes
seemed to have a protective effect against migraine
(OR 0·4) in migraineurs compared with non-
migraineurs.79 This and many of the other studies that
show comorbidities with headache have a cross-sectional
design, and interpretations of the results in terms of a
causal relationship must be made with caution.
Although obesity is a major risk factor for diabetes, it is
also thought to be associated with increased frequency
and intensity of migraine in clinical studies from the
USA. However, obesity is not comorbid with the diagnosis
of migraine itself.86 Nevertheless, the association between
a more complex group of patients with other chronic
headaches and obesity is more pronounced because
chronic headache is five times more prevalent in obese
individuals (body mass index >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

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
Review
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.
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