Original Article

Cephalalgia
31(16) 1664–1672
Treatment costs and indirect costs ! International Headache Society 2011
Reprints and permissions:

of cluster headache: A health economics sagepub.co.uk/journalsPermissions.nav

DOI: 10.1177/0333102411425866
cep.sagepub.com
analysis

Charly Gaul, Julia Finken, Janine Biermann, Sarah Mostardt,

Hans-Christoph Diener, Oliver Müller, Jürgen Wasem and
Anja Neumann

Abstract
Background: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic
(eCH) or chronic cluster headache (cCH) causing significant burden of disease and requiring attack therapy and
prophylactic treatment.
Methods: Treatment costs (direct costs) due to healthcare utilisation, as well as costs caused by disability and reduction in
earning capacity (indirect costs), were obtained using a questionnaire in CH patients treated in a tertiary headache
centre based at the University Duisburg-Essen over a 6-month period.
Results: A total 179 patients (72 cCH, 107 eCH) were included. Mean attack frequency was 3.5  2.5 per day. Mean
direct and indirect costs for one person were E5963 in the 6-month period. Direct costs were positively correlated
with attack frequency (r ¼ 0.467, p < 0.001). Burden of disease measured with HIT-6 showed a significant correla-
tion with attack frequency (r ¼ 0.467, p < 0.001). Twenty-four (13.4%) of the participants were disabled and not able
to work.
Conclusion: CH leads to major socioeconomic impact on patients as well as society due to direct healthcare costs and
indirect costs caused by loss of working capacity.

Keywords
Cluster headache, socioeconomic burden, cost of disease, direct costs, indirect costs
Date received: 28 June 2011; revised: 26 August 2011; accepted: 12 September 2011

Introduction 1 month occurs within 1 year (3). Treatment of CH

Cluster headache (CH) is the most frequent of the
so-called trigemino-autonomic cephalgias. The 1-year
prevalence of CH is about seven to 119 per 100,000. In
Germany about 5600 to 95,200 individuals were esti-
mated to be affected. CH shows male preponderance
(3.5:1) (1,2). It is characterised by severe unilateral
attacks of head and facial pain lasting for 15–180 min-
utes. Attacks are accompanied by prominent ipsilateral
cranial autonomic features (3). Most patients show
a striking circannual and circardian periodicity of clus-
ter attacks that may be caused by the underlying role
of the hypothalamus (4). Headache occurs in about
85% of patients as episodic cluster headache (eCH),
with a mean duration of the episodes of 8.6 weeks (5).
The remaining 15% suffer from chronic cluster
headache (cCH), in which no remission longer than
consists of two main principles: (i) aborting acute
attacks and (ii) prophylaxis. Attack treatment is per-
formed with oxygen inhalation, subcutaneous or intra-
nasal administration of triptans or intranasal lidocaine.
Prophylactic therapy includes verapamil or lithium as
treatment of first choice or steroids, topiramate, melato-
nin, long-acting triptans, and occipital nerve blocks (6,7).
A minority of patients will not respond sufficiently
University Duisburg-Essen, Germany.
Corresponding author:
Dr Charly Gaul, Department of Neurology, Headache Center, University
Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany
Email: Charly.Gaul@gmx.de
Gaul et al.
to the above-mentioned therapies and therefore be
considered refractory to attack treatment or prophy-
laxis (8). Invasive treatment options [occipital nerve
stimulation (ONS); deep brain stimulation (DBS)]
are suggested in some of these patients refractory to
prophylaxis (9).
Frequent and chronic CH causes a high burden of
disease as well as significant direct and indirect costs
within the healthcare system (10–12). There is, how-
ever, a shortage of data about direct and indirect costs
of CH, despite published single-case studies revealing
high expenses for acute and prophylactic treatment
(13,14). In a study from the headache centre in
Copenhagen, a significantly higher number of days
of work absence compared to the general population
and decreased work ability during cluster episodes
were reported in 82% of the patients. CH results in
disease-related lifestyle changes in 96% of patients
(12). Therefore, this study was carried out in a tertiary
headache centre in cooperation with a healthcare man-
agement institute to estimate the expenses for treat-
ment of eCH and cCH over a 6-month period.
Further aims were the relationship between costs,
burden of disease as well as attack frequency within
the 6-month period.
Methods
Study design
This retrospective study focused on direct and indirect
costs caused by CH. The observational period was
defined from 1 January until 30 June 2010. All included
patients were treated at the outpatient headache centre
of the Department of Neurology, University of
Duisburg-Essen, Germany, during this period by an
experienced neurologist who diagnosed the headache
type according to the ICHD-II criteria (3). The head-
ache centre provides medical care for patients with dif-
ficult-to-treat headaches referred by neurologists,
headache specialists or their insurance company in a
metropolitan region with about 5 million inhabitants.
Patients suffering from rare headaches or patients
refractory to regular treatment were referred from all
over Germany.
Inclusion criteria were: (i) diagnosis of CH, (ii)
age18 years at study time, (iii) adequate knowledge
of German language to understand interviews and
study purposes. All study participants were inter-
viewed about clinical characteristics, intake of acute
and prophylactic medication, consultations of medical
services, social environment and occupational back-
ground, absent days caused by CH within the above-
mentioned 6-month period and partial or complete
reduction in earning capacity. All interviews were
1665
done in July and August 2010. Informed consent
was obtained from all patients. The study was
approved by the local ethics committee. There was
no financial funding of this study.
Research instruments
The custom-made questionnaire consisted of 28 items,
including questions on socio-demography, and head-
ache-specific data (e.g. onset and history of disease, fre-
quency of attacks, acute and prophylactic medication).
The five-page survey was developed by the authors.
Time for completing the interview (face-to-face or tele-
phone) was estimated to be less than 30 minutes.
Interviews were performed by one trained medical stu-
dent (J.F.) or the first author (C.G.). In terms of
resource use, patients were asked about medications,
outpatient visits, hospitalisations, rehabilitation, phys-
iotherapy, osteopathy, absent days and reduction in
earning capacity (partial or complete). In Germany,
the definition of severely handicapped by law is
graded from 0 to 100%. This is recognised as an equal-
ising instrument offering various financial and other
benefits. For this reason, chronically ill patients fre-
quently apply for such a document. Therefore partici-
pants were asked about this topic. Additionally, the
Headache Impact Test (HIT-6), a standardised ques-
tionnaire for measurement of impact of headache and
headache-related disability, validated for use in
German language, was obtained (15). The HIT-6 con-
sists of six questions of which the first three ask for pain
intensity, restrictions in daily activities and the wish to
rest during headache attacks, whereas questions 4 to 6
ask for overall restrictions in daily life within the last 4
weeks. The headache impact severity level was cate-
gorised as follows: (a) little or no impact (49 or less),
(b) some impact (50–55), (c) substantial impact (56–59),
(d) and severe impact (60–78) based on the HIT-6 inter-
pretation guide (16).
The number of attacks was calculated for the
6-month period by multiplying attack frequency per
day with the individual period of cluster episode. The
calculated total number of attacks during the study
period was used as a measurement of impact of
headache.
Analysis of direct and indirect costs of cluster
headache
Direct and indirect costs of CH were calculated follow-
ing a bottom-up approach; healthcare costs were esti-
mated from a societal perspective. Intangible costs were
not included in this evaluation. Costs were calculated
for a time period of half a year. All costs are expressed
in Euros and adjusted for the year 2010.
1666 Cephalalgia 31(16)

Unit costs were obtained from a number of sources.
The costs of drugs were calculated based on the cheapest
package of each medication. Each dose was estimated at
1 mg and multiplied by a patient’s individual daily dose.
Items of the German medical fee schedule concerning
costs of resource use through outpatient contacts were
identified. Costs for hospitalisation were calculated
according to relevant Diagnosis Related Groups
(DRG) based on treatment of CH (G44.0) as the main
diagnosis. Rehabilitation costs were estimated by aver-
age costs for neuro-rehabilitation per day (17). In addi-
tion, indirect costs caused by disability and reduction in
earning capacity (partial or complete) were calculated
according to the friction cost approach. The friction
cost approach to estimating indirect costs means that
the price of labour is set at zero after the friction period
and is reduced to 80% during the friction period. We
estimated a friction period of 3 months (17). The calcu-
lations for the cost per day from the societal perspective
used average labour costs (18).
Furthermore, the impact of burden of disease and
correlation with attack frequency on treatment costs
was evaluated.
Costs of illness were calculated through multiplica-
tion of estimated prices and the resource consumption.
participation and 101 were unavailable for a face-to-face
or for a telephone interview. Patient characteristics are
shown in Table 1. The mean age of the men was 44  10.6
years, of the women 45  13.0 years (2 ¼ 62.076;
p ¼ 0.069). Age at onset of CH was 31.9  12.1 years.
Gender was no predisposition to develop cCH or eCH.
In the period reviewed, 135 patients had cluster
attacks with 63 patients (46.7%) belonging to the
eCH cohort. On average, patients had 3.5  2.5 attacks
per day (cCH: 3.8  2.6, eCH: 3.3  2.4; t ¼1.508;
p ¼ 0.133) with a range from 1 to 12 attacks per day.
The mean duration of bouts was 10.6  7.5 weeks with
a minimum of 1 week to a maximum of 6 months.
Attack-aborting medication was taken by 132
(73.7%) patients [(eCH: n ¼ 66 (61.7%); cCH: n ¼ 66
(91.7%)]. CCH patients took significantly more attack-
aborting medication than eCH patients (2 ¼ 20.783;
p < 0.001). The allocation of intake of attack-aborting
treatment and drugs is shown in Figure 1.
A total of 124 patients (69.3%) took prophylactic
medication [63 (87.5%) of the chronic, 61 (57%) of
the episodic patients (2 ¼ 19.602; p < 0.001)]. The
majority of the patients (n ¼ 47; 37.9%) were treated
with combinations of prophylactic medication. The

Statistics 70
cCH
Statistical analysis was done with the statistical package 60
eCH
SPSS PASW Statistics 18.0.0. Descriptive statistics are 50
presented as means  standard deviation (SD). Chi-
40
squared tests were used for comparison of categorical %
30
variables and t-tests for comparison of numerical vari-
ables. Correlation was used for coherences of several 20

variables among each other; p-values below 0.05 (two- 10

tailed) were defined as significant. 0
Oxygen Zolmitriptan Sumatriptan Sumatriptan
nasal spray s.c. nasal spray

Results cCH: chronic cluster headache; eCH: episodic cluster headache

Patient characteristics
Figure 1. Attack-aborting treatment and drugs in 132 chronic
Interviews were obtained from 179 of 285 CH patients and episodic cluster headache patients.
who were screened for the study. Five patients refused

Table 1. Patient characteristics

Total eCH cCH p-value

Study population 179 107 72 0.000

Age (mean) 44.7  11.2 years 44.5  10.8 years 45.0  11.8 years 0.773
Duration of disease 12.9  9.3 years 14.0  9.3 years 11.3  9.2 years 0.056
Male 126 82 (60.3%) 54 (39.7%) 0.869
Female 43 25 (58.1%) 18 (41.9%)
eCH: episodic cluster headache; cCH: chronic cluster headache.
Gaul et al. 1667

allocation of intake of different prophylactic drugs is
shown in Figure 2.
Exclusively consultations because of CH were cap-
tured for this study. The majority of patients received
outpatient treatment. They consulted the outpatient
headache centre of the Department of Neurology and
sometimes in addition physicians in private practice.
Fifty-three (73.6%) of the cCH patients consulted the
outpatient headache centre with an average number of
1.8  1.1 visits (range 1–6) during the 6-month study
period. Forty-one (38.3%) of the eCH patients con-
sulted the headache centre on average 1.9  1.7 times
with a range from 1 to 8 visits (p < 0.001). A neurologist
in private practice was consulted by 19 cCH patients
(26.4%, 4.4  6.7 visits per patient) and by nine eCH
patients (8.4%, 3.7  1.9 visits per patient). General
practitioners were consulted by 19 cCH patients
(26.4%, 12.4  17.3 visits per patient) and by 22 eCH
patients (20.6%, 7.6  12.6 visits per patient). A neuro-
surgeon was consulted by four cCH patients (5.6%,
1.8  1.0 visits) and by one eCH patient (two visits).
Six cCH patients (8.3%) visited a pain specialist
7.3  5.2 times and one eCH patient went to a pain
specialist five times.
In total, 15 of 179 patients (8.4%) were treated as
inpatients in the Departments of Neurology,
Neurosurgery or Neuro-Rehabilitation. Five cCH
(6.9%) with eight hospital stays had a mean duration
of 6.3  1.5 days (range: 3–7 days) in a Department of
Neurology and four eCH (3.7%) with five hospital
stays had a mean duration of 7.4  8.2 days (range:
1–21 days). Two cCH (2.8%) had two hospital stays
in a Department of Neurosurgery with a mean duration
each time of 10  1.4 days (range: 9–11 days). Inpatient
treatment in a Department of Neuro-Rehabilitation
was done by 4 cCH (5.6%) with a mean duration of
29.8  8.8 days (range: 21–42 days).
Costs per patient in the 6-month period
Per capita acute and prophylactic medication costs in
the 6-month period are shown in Tables 2 and 3).

Total costs for all patients in the 6-month period

The following data refer to overall costs of all partici-
80 pants, namely 179 patients (72 cCH and 107 eCH
cCH
70
eCH
patients). The costs of acute medication account for a
60
total of E694,582 (cCH: E531,288 and eCH: E163,294)
50
% 40 (Figure 3).
30
The costs of prophylaxis accounted for a total of
20 E39,378 (cCH: E26,171 and eCH: E13,206). Most of
10 these costs are attributed to verapamil
0 (E14,199 ¼ 45.3%) (Figure 4).
Another item of expense is the outpatient treatment;
il

in

tin

te
am

at

on
iu

oa
en
m
th

E18,234 were spent for all participants, E10,922 for

p

at

r
ap
ira

lp
ra

Li

el

Va
Ve

ab
p

M
To

cCH patients and E7312 for eCH patients (Table 4).

cCH: chronic cluster headache; eCH: episodic cluster headache In addition, costs for technical tests such as com-
puter tomography, nuclear magnetic resonance imag-
Figure 2. Prophylaxis with drugs in chronic and episodic ing, long-term ECG and others (E1777),
cluster headache patients (n ¼ 124). physiotherapy, massage and manual therapy (E4914),

Table 2. Costs of attack-aborting treatment per capita; drug treatment is dose-adjusted

6-month treatment 6-month treatment 6-month treatment

Medication cost/per capita cost/patient with cCH cost/patient with
(number of mean daily intake) (n) (n) eCH (n)

Oxygen (3.6 * inhalation) E416 (92) E533 (45) E334 (47)

Zolmitriptan nasal spray (1.5 * 5 mg) E2571 (58) E4318 (27) E1790 (31)
Sumatriptan s.c.(1.8 * 6 mg) E11,556 (41) E14,457 (27) E8901 (14)
Sumatriptan nasal spray (1.5 * 20 mg) E1459 (9) E3044 (3) E1332 (6)
eCH: episodic cluster headache; cCH: chronic cluster headache.
In parentheses (n) are the numbers of patients who were treated with prophylactic medication.
1668 Cephalalgia 31(16)

Table 3. Costs of prophylactic medication for different treatments per capita

Medication/drug 6-month treatment 6-month treatment 6-month treatment cost/patient

(mean daily dose) cost/per capita (n) cost/patient with cCH (n) with eCH (n)

Verapamil (474 mg) E134 (106) E175 (51) E96 (55)

Lithium (746 mg) E79 (11) E80 (9) E78 (2)
Topiramate (178 mg) E180 (35) E227 (21) E110 (14)
Melatonin (35 mg) E1290 (4) E1290 (4) *
Gabapentin (2467 mg) E330 (4) E413 (2) E248 (2)
Valproate (1067 mg) E86 (7) E93 (6) E42.12 (1)
Steroid pulse therapy E113 (69) E139 (23) E99.73 (46)
Occipital nerve block E16 (15) E16 (12) E15 (3)
*Not used by any patient; eCH: episodic cluster headache; cCH: chronic cluster headache.
In parentheses (n) are the numbers of patients who were treated with prophylactic medication. Drug costs are dose-adjusted.

500000 16000 eCH

450000 eCH
14000
400000 cCH
350000 cCH 12000
€ 300000 10000
250000 € 8000
200000
150000 6000
100000 4000
50000 2000
0
0
sc
ay

ay

s
n

er
ge

y
il

tin

ck
pr

pr

in

te
n

s
ap
am
th

at
ta

er
iu

on
xy

oa
ls

ls

o
en
O

er
rip

bl
th

th
p
O

sa

sa

at

pr
ap
ira
ra

th
Li

O
ve
at

el

l
na

na

Va
Ve

ab
p
m

e
M

er
To

ls
Su
n

ln
pu
ta

ta

ita
ip

rip

id
itr

ip
at

io
lim

cc
m

er

O
Su

St
Zo

eCH: episodic cluster headache; cCH: chronic cluster headache

eCH: episodic cluster headache; cCH: chronic cluster headache Others: antidepressants, opioids, long-acting triptans,
Others: analgesics, oral triptans, xylocaine spray methysergide, beta-blocker

Figure 3. Allocation of total costs for several attack-aborting Figure 4. Allocation of total costs for several prophylactic
treatments (per 6 months). medications (per 6 months).

Table 4. Costs and reimbursement for care of patients

Insurance reimbursement Privately-insured

for 3-month period patient per visit

Headache centre E92.84 1. visit: E100.71

2. visit: E48.03
Neurologist E31.54 1. visit: E100.71
2. visit: E48.03
General practitioner E31.54 E30.60
Neurosurgeon E31.54 E48.03
Pain specialist E58.71 n/a
Gaul et al.
Table 5. Total costs
All participants Per capita
Direct costs E847,905 E4737
Indirect costs E219,412 E1226
All costs E1,067,317 E5963
*cCH: chronic cluster headache; eCH: episodic cluster headache.
alternative practitioner and osteopath (E2470) and acu-
puncture (E2261) were calculated.
The total costs for inpatient treatment were E1505
for admission to the Department of Neurology,
E20,349 for the neurosurgery procedure of bilateral
occipital nerve stimulation and for inpatient rehabilita-
tion E156 per day. Hospitalisation for headache treat-
ment amounted to E24,086. Rehabilitation amounted
to E18,556.
Two patients suffering from refractory CH were
treated by occipital nerve stimulation within the
period of the study (19). The costs of surgery and
hospitalisation were E40,578.
Indirect costs for all participants in the 6-month
period
Twenty-four (13.4%) patients were severely handi-
capped (23 patients 100%, one patient 50%) during
the observation period (cCH: n ¼ 16, eCH: n ¼ 8).
Based on a daily loss of E95, a total of E160,740 results
for all the patients concerned. Moreover, 34 patients
indicated having been unable to work for a few days/
weeks, resulting in E58,672 for all participants. On
average patients were absent from work due to illness
for 8.5 days.
Mean direct and indirect costs for a single CH
patient are E5963 over 6 months. Costs were much
higher for cCH patients (E10,985) than for eCH
patients (E2583) (Table 5).
Additional results
The total score in the HIT was on average 56.68  8.81
(range 41–78), for cCH on average 61.78  8.05 (45–76),
for eCH on average 53.25  7.57 (41–78) for all
participants.
There was no significant correlation between number
of attacks per day and burden of disease measured by
HIT-6. cCH patients had significantly higher scores in
the HIT-6 than eCH patients (t ¼7.288; p < 0.001).
A significant correlation was found between the total
score of the HIT-6 and direct costs (r ¼ 0.293,
p < 0.001) and between the total score in the HIT-6
1669
cCH Per patient with cCH eCH Per patient with eCh
E653,264 E9073 E194,641 E1819
E137,636 E1912 E81,776 E764
E790,900 E10,985 E276,417 E2583
and number of attacks in the 6-month period
(r ¼ 0.467, p < 0.001).
Furthermore, a significant correlation was found
between number of attacks in the 6-month period and
the direct costs (r ¼ 0.467, p < 0.001).
Forty-two patients (24%) had been officially classi-
fied as severely handicapped due to CH (eCH
12 patients; cCH 30 patients). The average degree was
40.2% for CH. The median degree is 30% in eCH
patients and 50% in cCH patients.
Discussion
There are only very limited published data on economic
consequences of CH. In our study direct and indirect
costs in CH patients were high, with significantly more
expenses for patients suffering from cCH.
Direct costs were predominantly a result of the
expenses for attack treatment with triptans (especially
when used as subcutaneous injections) and oxygen for
attack treatment. In our study, most of the expenditure
was caused by costs for triptans (75%), followed by
oxygen (4.5%). In comparison with this, costs of pro-
phylaxis were much lower (verapamil 1.7%, topiramat
0.01%, others < 0.01%). The overall expenses for acute
treatment per capita were E3880 compared to E220 for
prophylaxis within the 6-month period. This is in line
with reported long-term costs of one patient suffering
from secondary cCH in Germany over a 10-year
period. The individual amounts are composed of costs
for drugs and oxygen (89.7%), diagnostics (5.5%) and
medical fees (4.8%) (13). During this time, the patient
suffered 5447 attacks with overall costs of E47,030, rep-
resenting 77.5% of all his medical costs during this
period (even including other diseases) (13).
Reimbursement of treatment costs of any of the used
substances for acute and prophylactic treatment as well
as for oxygen in Germany are generally covered by
health insurances. For some patients, reimbursement
for oxygen is granted only after extensive discussions
with the insurance company; but in the end, all patients
receive reimbursement.
This is different from other countries. A recently
published US-American trial on the use of oxygen for
acute treatment of CH revealed that the costs were
1670
covered by their medical insurance for only 64% of
oxygen users; 61% of CH patients stated that obtaining
reimbursement was not difficult, while 7% stated it was
very difficult. Total costs for oxygen were estimated at
less than $1000 in 65% of the patients, in 31% between
$1000 and $6000 and in 2.5% between $8000 and
$12000 per year. Out-of-pocket costs covered by the
patients themselves were less than $1000 in 87%,
while 13% spent between $1000 and $12,000 (20).
Comparing with our data, most of our participants
had total costs for oxygen under $1000 per 6 months.
Average costs were E416 (¼$600). Only 5.6% of all
participants had costs above $1000. In the US survey,
use of non-medical oxygen, which is much cheaper, is
reported in 12% of patients. Reasons for this are lower
costs (stated by 66% of the patients), inability to go to
the doctor to get a prescription (22%) and physician’s
unwillingness to prescribe (18%). Since the question
was not asked in our study, we have no comparable
data.
Effective prophylactic medication that results in a
50% or more reduction in attack frequency may
reduce the total costs enormously. However, a prospec-
tive trial or a matched-pairs analysis is necessary to
prove this assumption. In terms of treatment costs,
CH is a very expensive disease even if it is not a fre-
quent headache disorder.
Only a few patients were treated as inpatients
(6.2%), which might be a higher portion of patients
in a population not treated in a specialist headache
centre. Costs for patients suffering from refractory
CH were similar to costs reported in other studies.
An Italian headache centre reported direct costs of
hypothalamic stimulation of about E27,000 per patient
(14), whereas costs of bilateral occipital nerve stimula-
tion were calculated at about E20,000 in our study.
To the best of our knowledge, no detailed cost anal-
ysis of other headache disorders is available from
Germany. To demonstrate the dimension of costs per
capita of eCH and cCH, a comparison with healthcare
costs of multiple sclerosis in Germany was performed.
Estimated direct healthcare costs were E17,165, direct
non-medical costs E5922 and costs due to productivity
losses E16,911, resulting in total mean annual costs per
patient of E39,998 (21). Furthermore, annual direct
mean costs of patients with diabetes mellitus, as a
non-neurological condition, were E5262 and indirect
costs were E5019 per patient, which yields a total of
E10,281 for the German healthcare system (22).
A recently published internet-based survey on costs
of migraine in the US and Canada revealed $1036
within 3 months for chronic and $383 for episodic
migraine in the US and $471 and $172 respectively in
Canada (23). Even considering that direct comparison
of healthcare costs between different countries is limited
Cephalalgia 31(16)
to different local statutory requirements, costs of
CH are higher than expenditures for migraine care.
Twenty-four patients (13.4%) were severely handi-
capped. Incapacity to work or early retirement was
reported in 34 (19%) of the patients in our cohort
within the 6-month period, whereas the Danish study
reported early retirement in 8% and work absences
during 1 year in 29.6% (12).
With approximately 5600 to 95,200 affected individ-
uals and the assumption that 10% suffer from cCH and
90% from eCH, between ME14 and 242 would accrue
in cumulative costs for treatment of CH in Germany
alone. Consistent with the episodic character of CH,
not every patient suffers active periods every year.
Moreover, we used the worst value for each item in
our study, which results in slightly higher values for
several items (like attack frequency). The absolute
costs in Germany might actually be lower than those
calculated in our study. In addition, due to misdiagno-
sis and under-diagnosis of CH, many patients will not
have been treated (24). On the other hand, many
patients may receive inadequate treatment in several
disciplines, resulting in high expenses. Costs for unnec-
essary technical investigations (imaging), visits to the
dentist and others do not accrue at a tertiary centre.
Treatment costs from the societal perspective are the
focus of our study. From the patients’ perspective, the
burden of disease, pain intensity and attack frequency
are the main topics. High burden of disease, especially
in chronic patients, results in long-lasting impairment,
social dysfunction, reduced quality of life and psychi-
atric co-morbidity. A recent study revealed invalidity in
25% of cCH patients due to CH. Depressive symptoms
(56%), signs of agoraphobia (33%) and suicidal ten-
dencies (25%) were frequently reported (11). In this
study, 11.2% (12 patients) of the eCH and 41.7% (30
patients) of cCH patients were severely handicapped (as
defined by law).
Our study indicates that the HIT is a suboptimal test
for estimating the burden of disease in CH. HIT-6
scores did not correlate significantly with attacks per
day, which might be the most objective factor of a
patient’s restriction in daily life. This could be caused
by the last three questions in HIT-6 based on the pre-
vious 4 weeks. Patients suffering from eCH who were
out of bout in the previous month before the interview
rated lowest possible scores, while patients suffering
from cCH or eCH patients who were in bout were
more likely to choose the highest given scores. That
does not indicate less restriction in life during bouts
with an attack frequency of up to eight times per day.
Therefore the total score of the HIT-6 is not a good
predictor. Looking at costs, the number of attacks in
the 6-month period has a much better predictive value
than the HIT-6. It might have been better to use the
Gaul et al.
Headache Disability Inventory because it refers to an
unspecified period in the past (25).
Methodological considerations
There are several limitations to this study. All patients
in our survey were treated in a tertiary headache centre.
Therefore, the proportion of cCH patients is much
higher in our cohort (eCH 60%: 40% cCH) than
expected from population-based studies, which
showed cCH in 10–20% (26). This is a selection bias
resulting from recruiting patients in a tertiary centre.
Allowing for a higher proportion of cCH patients in a
tertiary headache centre may result in more patients
refractory to treatment. There is no generally accepted
definition of ‘refractory cluster headache’; suggestions
made in the literature refer to a minimum number of
medications, but do not specify the dose (27). Two
patients within the study were refractory to treatment
and consented to being treated with bilateral occipital
nerve stimulation. Unfortunately, detailed analysis of
additional refractory patients was not done. One can
speculate that refractory patients need more (and more
expensive) attack treatment (especially sumatriptan
s.c.) and are more permanently disabled compared to
others. However, age and gender distribution of our
cohort represents a typical CH cohort compared to lit-
erature and our study population may therefore be
comparable to other clinical populations (28). A further
limitation of this survey is the retrospective character of
the study – but over a 6-month period, data might be
reliable. However, quality of data could be improved in
further studies, by using prospective headache and
treatment diaries.
Major advantages of this study are the high validity
of the headache diagnosis, which strictly followed the
ICHD-II, and the validity of the detailed analyses of
direct and indirect costs.
We conclude that patients with CH are severely
impaired regarding the frequency of attacks and cause
a high economic burden. Thus, cCH in particular war-
rants special medical and further supportive care to
reduce the burden of disease as well as direct and indi-
rect treatment costs. From the medical and the socio-
economic point of view headache centres taking care of
a higher number of patients may reduce impairment
and economic consequences of the devastating pain dis-
ease CH. Future studies are needed to substantiate this
assumption.
Conflict of interest
The authors declare that there is no external funding and no
conflict of interest regarding the contents of this manuscript.
1671
References
1. Russell BM. Epidemiology and genetics of cluster head-
ache. Lancet Neurol 2004; 3: 279–283.
2. Katsarava Z, Obermann M, Yoon MS, et al. Prevalence
of cluster headache in a population-based sample in Ger-
many. Cephalalgia 2007; 27: 1014–1019.
3. Headache Classification Subcommittee of the International
Headache Society. The International Classification of
Headache Disorders. 2nd edn. Cephalalgia 2004;
24(Suppl 1): 9–160.
4. Holland PR and Goadsby PJ. Cluster headache, hypo-
thalamus, and orexin. Curr Pain Headache Rep 2009; 13:
147–154.
5. Bahra A, May A and Goadsby PJ. Cluster headache: a
prospective clinical study with diagnostic implications.
Neurology 2002; 58: 354–361.
6. May A, Leone M, Afra J, et al. EFNS guidelines
on the treatment of cluster headache and other trigemi-
nalautonomic cephalalgias. Eur J Neurol 2006; 13:
1066–1077.
7. Gaul C and Jürgens T. Frovatriptan for prophylactic
treatment of cluster headache. Headache 2011; 51:
1008–1009.
8. Goadsby PJ, Schoenen J, Ferrari MD, et al. Towards a
definition of intractable headache for use in clinical prac-
tice and trials. Cephalalgia 2006; 26: 1168–1170.
9. Jürgens T, Paulus W, Tronnier V, et al. Neuromodula-
tion in primary headache – treatment recommendation of
the German Migraine and Headache Society.
Nervenheilkunde 2011; 30: 47–58.
10. Stovner LJ and Andrée C. Eurolight Steering Committee.
Impact of headache in Europe: a review for the Eurolight
project. J Headache Pain 2008; 9: 139–146.
11. Jürgens TP, Gaul C, Lindwurm A, et al. Impairment in
episodic and chronic cluster headache. Cephalalgia 2011;
31: 671–682.
12. Jensen RM, Lyngberg A and Jensen RH. Burden of clus-
ter headache. Cephalalgia 2007; 27: 535–541.
13. Jürgens TP and May A. Chronic cluster headache: how
much does treatment cost? Schmerz 2010; 24: 221–225.
14. Leone M, Franzini A, Cecchini AP, et al. Costs of hypo-
thalamic stimulation in chronic drug-resistant clus-
ter headache: preliminary data. Neurol Sci 2009;
30(Suppl 1): 43–47.
15. Martin M, Blaisdell B, Kwong JW, et al. The Short-Form
Headache Impact Test (HIT-6) was psychometrically
equivalent in nine languages. J Clin Epidemiol 2004; 57:
1271–1278.
16. Bayliss M and Batenhorst A. The HIT-6TM: a user’s
guide. USA: QualityMetric, Inc: Lincoln, RI, 2002.
17. Krauth C, Hessel F, Hansmeier T, et al. Empirical stan-
dard costs for health economic evaluation in Germany –
a proposal by the working group methods in health
economic evaluation. Gesundheitswesen 2005; 67:
736–746.
18. VGR des Bundes – Arbeitnehmerentgelt, Löhne und
Gehälter (2010). Available at: https://www-genesis.desta-
tis.de/genesis/online;jsessionid¼126420C083BD1864
1672
FA00670A1E5BD6A6.tomcat_GO_1_2?operation¼pre-
vious&levelindex¼2&levelid¼1306932724985&step¼2
(accessed March 2011).
19. Mueller OM, Gaul C, Katsarava Z, et al. Occipital nerve
stimulation for the treatment of chronic cluster headache
– lessons learned from 18 months experience. Cen Eur
Neurosurg 2011; 72: 84–89.
20. Rozen TD and Fishman RS. Inhaled oxygen and clus-
ter headache sufferers in the United States: Use, effi-
cacy and economics. Results From the United
States Cluster Headache Survey. Headache 2011; 51:
191–200.
21. Kobelt G, Berg J, Lindgren P, et al. Costs and quality of
life of multiple sclerosis in Germany. Eur J Health Econ
2006; 7(Suppl 2): S34–S44.
22. Köster I, von Ferber L, Ihle P, et al. The cost burden of
diabetes mellitus: the evidence from Germany – the
CoDiM study. Diabetologia 2006; 49: 1498–1504.
23. Stokes M, Becker WJ, Lipton RB, et al. Cost of health
care among patients with chronic and episodic migraine
Cephalalgia 31(16)
in Canada and the USA: Results from the International
Burden of Migraine Study (IBMS). Headache 2011; 51:
1058–1077.
24. Bahra A and Goadsby PJ. Diagnostic delays and mis-
management in cluster headache. Acta Neurol Scand
2004; 109: 175–179.
25. Jacobson GP, Ramadan NM, Aggarwal SK, et al. The
Henry Ford Hospital Headache Disability Inventory
(HDI). Neurology 1994; 44: 837–842.
26. Bussone G, Rapoport A. Acute and preventive treatment
of cluster headache and other trigeminal autonomic
cephalagias. In: Nappi G, Moskowitz MA (eds)
Handbook of Clinical Neurology, Volume 97, 3rd edn.
2011.
27. Goadsby PJ, Schoenen J, Ferrari MD, et al. Towards a
definition of intractable headache for use in clinical prac-
tice and trials. Cephalalgia 2006; 26: 1168–1170.
28. Ekbom K, Svensson DA, Träff H, et al. Age at onset and
sex ratio in cluster headache: observations over three dec-
ades. Cephalalgia 2002; 22: 94–100.